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Outcomes Research in Lung Cancer

Outcomes Research in Lung Cancer Abstract Background: Lung cancer is the leading cause of cancer death in the United States. Most therapeutic interventions for this disease achieve modest benefits, but at the expense of nontrivial toxicity and cost, making it an important area for outcomes analysis. Objective: The goal of the study was to audit the literature of outcomes pertaining to lung cancer. Data sources: The English language outcomes literature published during the period from 1990 through 2000 was systematically reviewed and analyzed. Study selection: Papers had to contain original research in one of the following areas: quality of life, health economics, communication, decision making, quality of care, or patient satisfaction. Data extraction: The literature was reviewed and analyzed by the author. Data synthesis: The lung cancer outcomes literature is growing rapidly. Of the 199 studies examined, 106 (53%) dealt primarily with quality-of-life measurement, 69 (35%) examined costs, 11 (6%) dealt with communication and decision making, 11 (6%) assessed the quality of care, and two (1%) evaluated patient satisfaction. Most studies focused on the palliative phase of care. Women, the elderly, and minorities were generally well represented in these studies. The European Organization for Research and Treatment of Cancer QLQ-C30 with its LC13 module is emerging as the most commonly employed quality-of-life instrument in lung cancer studies. Economic studies vary widely in their quality. The literature is relatively sparse with respect to quality of care, communication, and decision making, however. Conclusions: A substantial body of outcomes research has been published since 1990. Further work is needed in the area of methods development, in the assessment of the impact of new technologies, and in the monitoring of the quality of lung cancer care in vulnerable populations. Lung cancer is the leading cause of cancer death in the United States (1). Small-cell lung cancer (SCLC) accounts for approximately 20% of cases, and the balance of cases are referred to as non-small-cell lung cancer (NSCLC), composed mostly of squamous, adenocarcinoma, and large-cell histologies. Most patients present with incurable disease at the time of diagnosis and, because of early hematogenous spread, even those presenting with “ early”-stage disease will often eventually develop incurable metastases (2). The 5-year survival rate for all lung cancer patients is only 15% and has not improved greatly during the past 30 years despite much effort in prevention and therapeutics (3). Surgery is the only treatment modality that can consistently cure a small number of patients with early NSCLC, although radiation therapy can be curative in some limited circumstances. Chemotherapy may contribute in an adjuvant or neoadjuvant role, but it is used mostly as a palliative therapy for advanced disease. SCLC, on the other hand, is more chemosensitive and can be cured in a minority of patients with chemotherapy and radiation therapy. Nevertheless, most patients relapse and die within 1 year of diagnosis (2). Treatments for all stages and histologies of lung cancer are difficult and expensive and come with nontrivial toxicity. Physicians have traditionally evaluated interventions by looking at their effects on tumor shrinkage, time to disease progression, and survival. However, the unsatisfactory results of most lung cancer therapies have led to increasing interest in other end points that affect decision making by patients, payers, and regulators. In this study, I focused on the following broad categories: 1) quality of life, 2) health economics, 3) quality of care, and 4) communication and decision making, as they pertain to lung cancer. This study examines the use of these end points in methodological, descriptive, and intervention studies, as well as economic and decision analyses in order to understand the impact of lung cancer on patients, families, providers, and payers. Methods Literature Search A computerized literature search was done centrally at the National Library of Medicine. It was designed to look for Medical Subject Headings (MeSH) relevant to outcomes research in lung cancer, restricted to English-language articles with on-line abstracts using the following strategy: (quality of life [mh] OR survival analysis [majr] OR health status [mh:noexp] OR health status indicators [mh] OR activities of daily living [mh] OR decision support techniques [majr:noexp] OR decision theory [majr] OR decision making [majr:noexp] OR choice behavior [majr] OR medical futility [majr] OR economics [majr:noexp] OR “costs and cost analysis” [majr] OR cost-benefit analysis [majr] OR economic value of life [majr] OR economics, hospital [majr] OR economics, medical [majr] OR economics, nursing [majr] OR economics, pharmaceutical [majr] OR health services research [mh:noexp] OR delivery of health care [majr:noexp] OR attitude to death [majr] OR attitude to health [majr] OR “health services needs and demand” [majr] OR needs assessment [majr] OR professional-patient relations [majr] OR patient satisfaction [majr] OR physician-patient relations [majr] OR quality of health care [majr:noexp] OR medical audit [majr] OR nursing audit [majr] OR “ outcome and process assessment (health care)” [majr] OR peer review, health care [majr] OR professional review organizations [majr] OR program evaluation [majr] OR quality assurance, health care [majr:noexp] OR guidelines [majr] OR total quality management [majr] OR quality indicators, health care [majr]) AND lung neoplasms [majr] AND english [la] AND journal article [pt] AND 1990: 2000[pdat] AND has abstract. Personal reprints and reference lists were also reviewed. Data Abstraction The study was carried out in two steps. First, for a report to the Outcomes Branch of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, the literature was searched in August 1999 for all articles published during the period from January 1990 through August 1999. In January 2001, this literature search was updated to include all studies published through the end of December 2000. All abstracts were examined, and relevant articles were retrieved. Papers were subsequently excluded if they were found to be reviews, editorials, or opinion pieces or if they were judged not to be outcomes research. Studies that claimed to measure quality of life but did so without an instrument (i.e., relying on the general impressions of the physicians) or that only measured performance status were excluded. Predetermined data elements were abstracted and entered immediately into an electronic database. These included the intervention studied, the type of outcome assessed, measurement instruments used, the study design and perspective, years of data collection, sample size, stages and histology of lung cancer in the study population, percentage of female subjects, percentage of nonwhite subjects, average age of the patients, and a short description of the study findings. For the updated review (August 1999 through December 2000), additional data elements were abstracted, such as the phase of care being addressed by the study, whether the sample size was based on an a priori power calculation, and whether confidence limits were presented around measured estimates. Database manipulation and analyses were carried out by using the Statistical Analysis Software, version 8.01 (SAS Institute, Cary, NC, 1999). Results Literature Search The literature search yielded 860 articles, of which 210 were deemed appropriate for retrieval and review on the basis of the abstract. Of these, 11 were excluded: Six were reviews (4-9), one was an opinion piece (10), and four did not have any true outcomes component (11-14). The remaining 199 studies are described in the Appendix. One hundred six studies (53%) dealt primarily with quality-of-life measurement, followed in number by the 69 (35%) papers that examined costs (Table 1). There were 11 (6%) studies dealing with communication and decision making, 11 (6%) assessing the quality of care, and two (1%) evaluating patient satisfaction. There has been a rise in the number of studies published each year over the course of the decade, most noticeable in the quality-of-life literature (Fig. 1). Table 1. Types of outcomes studies (n = 199) Study   No.   %   Quality of life   106   53   Economic   69   35   Communication/decision making   11   6   Quality of care   11   6   Patient satisfaction   2   1   Study   No.   %   Quality of life   106   53   Economic   69   35   Communication/decision making   11   6   Quality of care   11   6   Patient satisfaction   2   1   View Large Fig. 1. View largeDownload slide Numbers of outcomes studies over time. CEA = cost-effectiveness analyses; QoL = quality-of-life analyses. Fig. 1. View largeDownload slide Numbers of outcomes studies over time. CEA = cost-effectiveness analyses; QoL = quality-of-life analyses. Most studies focused on NSCLC (108 studies, 54%), although many examined both histologies (63 studies, 32%). More than half of the studies (51%) examined patients with all stages of disease, and more than 30% were restricted to the study of advanced, incurable cancer. A prospective cohort study design was most common, being used in 61 (31%) of the studies, followed by quality-of-life or economic companions alongside randomized controlled trials (43 studies, 22%). Sixteen studies (8%) were carried out prospectively alongside phase I or II trials. Thirty-one decision analyses (16% of studies), all but one an economic evaluation, were reported. Retrospective cohorts were assembled in 26 (13%) studies, and 16 studies (8%) carried out cross-sectional surveys. Most studies came from the United States (68 studies, 34%), followed by Canada (33 studies, 17%), and the United Kingdom (25 studies, 13%). The distribution was similar for all outcomes. Eight studies (4%) were international. For studies that included patients, the average sample size was 523; however, this varied widely. Studies of quality of care (mean = 3560 patients) and cost (mean = 624 patients) tended to be the largest. Quality-of-life studies averaged 206 patients, and studies of decision making and communication had 254 patients on average; satisfaction was evaluated in an average of 37 patients. The mean age of patients in lung cancer outcomes studies was 63 years, and 30% of patients were women. There were three studies, all from the same author, that examined quality-of-life issues in cohorts made up exclusively of women (15-17). Only 24 articles (12%) commented on the racial makeup of their study population. All but one, a communication study from the United Kingdom, were U.S. quality-of-life papers. Of those studies that did report a racial distribution, an average of 15% of patients were nonwhite (range, 1%-38%). The age, sex, and racial demographics of patients studied did not differ greatly across the different types of outcomes studies. Levels of comorbidity were generally not reported. Eighty-four percent of the studies dealt with treatment, and 13% evaluated staging work-up. The rest were evenly split between studies of diagnosis and prevention. A priori power calculations for the outcomes end point were made in 13% of prospective randomized studies and in 40% of cross-sectional surveys. A power calculation was never reported as being a consideration in other study designs, such as phase II studies or prospective cohort analyses. Quality of Life Quality-of-life studies were most likely to examine patients with “ lung cancer” not restricted to homogeneous stage (46% of the time) and often were not restricted to a common histologic group either (30% of the time). Of note, more than one-quarter of the studies were primarily methodological in nature. As expected, the majority of quality-of-life studies were prospective, and 27% involved quality-of-life assessment alongside a randomized trial. Another 16% were carried out alongside phase I and II trials. Fifty-seven percent of the studies presented quality-of-life estimates with some indication of variability (e.g., confidence intervals and standard deviation), whereas 43% did not. Instruments More than one-half of the studies used more than one instrument. Forty-one percent used two, and 13% used three or more, for an average of 1.7 instruments per study. When two or more instruments were used in the same study, they were usually used as complementary instruments in a clinical trial. Although generally not paired for methodological reasons, the different instruments tended to show convergent results. The European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire (EORTC QLQ-C30), either alone or with its lung cancer subscale, the LC13, clearly dominates the literature, being used in 39 (37%) studies (Table 2), especially in more recent studies. The next most commonly used scales were the Rotterdam Symptom Checklist (RSC) and the Hospital Anxiety and Depression Scale (HADS), which were often used together in British studies in the early 1990s, along with the British Medical Research Council (MRC) daily diary card. U.S. studies tended to use the domestically developed Lung Cancer Symptom Scale (LCSS) or Functional Assessment of Cancer Therapy with its lung cancer subscale (FACT-L). In six studies, the investigators developed unique, unvalidated instruments to measure quality of life. Table 2. Most frequently used instruments for quality-of-life assessment in lung cancer (n = 106 studies) Measure*  No.†   %   *EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module.   † More than one instrument could be used in a study.   EORTC QLQ-C30   39   37   EORTC LC13   19   18   Rotterdam Symptom Checklist   13   12   Hospital Anxiety and Depression Scale   12   11   Lung Cancer Symptom Scale   9   8   Linear Analogue Self-Assessment   8   8   British Medical Research Council daily diary card   7   7   Functional Living Index—Cancer   6   6   FACT-G and FACT-L   5   5   Spitzer Index   4   4   Measure*  No.†   %   *EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module.   † More than one instrument could be used in a study.   EORTC QLQ-C30   39   37   EORTC LC13   19   18   Rotterdam Symptom Checklist   13   12   Hospital Anxiety and Depression Scale   12   11   Lung Cancer Symptom Scale   9   8   Linear Analogue Self-Assessment   8   8   British Medical Research Council daily diary card   7   7   Functional Living Index—Cancer   6   6   FACT-G and FACT-L   5   5   Spitzer Index   4   4   View Large Findings To date, the results of many of the quality-of-life studies seem predictable. In observational studies, patients starting out with poor quality of life were less likely to receive aggressive treatment. However, health care professionals can underestimate quality of life compared with patient self-reports (18). Furthermore, quality of life can change rapidly and, therefore, should be measured frequently (at least every 3-4 weeks) to get an accurate picture of the disease course (19). A common finding in randomized studies was that the toxicity of treatment was counterbalanced by decreased tumor-related symptoms (4,20-22). Quality of life can improve even with stable disease (23). Quality-of-life studies rarely changed the outcome of an analysis, but there were some examples where both treatment arms yielded similar survival results, and the quality-of-life effects determined the preferred strategy (24,25). The ability of quality-of-life measures to predict response and survival has been shown many times (26-34). Missing data as a result of patient deterioration were frequently cited as a technical problem, however, often resulting in compliance of around 50% or less (22,24,33, 35-43). Simple daily diary cards have been reported to have better completion rates (25,44). Costs Cost studies have tended to focus on NSCLC. There was a flurry of publications on NSCLC in the middle of the decade, which seems to have leveled out somewhat recently. The plurality of papers (43%) reported decision analytic disease and economic models, although a total of 22% collected prospective or retrospective data alongside randomized clinical trials. It is interesting that only eight (12%) of the 69 economic studies reported a clearly negative result for the intervention being assessed (45-52). Fifty-five percent of studies looked only at the resources consumed by lung cancer care or at cost-minimization between two management options, without consideration of treatment effects. Thirty-eight percent were cost-effectiveness studies with some measure of the consequences of intervention in the denominator. Methodologies differed widely between studies. Only two (3%) attempted to incorporate patient preferences in a cost-utility analysis (50,53). These did not use validated utility instruments like the EQ-5D (EuroQol) or the Health Utilities Index (HUI). A non-economic methodological study using data from a lung cancer trial tried to map the RSC and HADS to the EQ-5D and HUI, however (54). Most studies (93%) took the payer's perspective. Only four studies (6%) took a societal perspective, including costs such as patient time and transportation expenses in the numerator (55-58). The rest of the studies either looked at patient's out-of-pocket costs, or the perspective could not be inferred. Still, the types of costs included in these analyses were inconsistent, with some studies, for example, reporting results that excluded the costs of the study drug (59-61). Subjectively, the quality of studies including an economic component varied widely, with several simply stating cost estimates without any methods discussed (62-64). Because of the short survival time of most patients, lung cancer was commonly found to be a relatively inexpensive disease to manage on a cost-per-case basis. However, because of its prevalence, it constitutes an important proportion of total health care expenditures (61). Hospitalization consistently emerged as the main driver of cost. Interventions such as palliative chemotherapy can lead to patients spending fewer days in hospital and requiring less palliative radiotherapy, thus offsetting the cost of the intervention (65). Quality of Care and Satisfaction There were 11 studies dealing with quality-of-care issues and two studies concerned with patient satisfaction. The most consistent theme to emerge from these studies was that there is variation in practice patterns based on both valid medical considerations like age (66-68) and nonmedical factors like race (69), geographic location (70,71), socioeconomic status (72), and the type of physician being consulted (73). Patient satisfaction was found to be enhanced by using quality-of-life surveys taken during visits to the clinic (74) and by identifying how involved patients wanted to be in the decision-making processes (75). Communication and Decision Making The 11 articles pertaining to decision making and doctor—patient communication focused on areas where the treatment decision is controversial, such as multimodality treatment for locally advanced NSCLC and palliative chemotherapy for advanced disease. These studies were generally carried out by using structured interviews, and they reinforced the notion that patients want information about their disease and want to participate in decision making, although there is important individual variation in how involved they want to be. Discussion This systematic review has found that there is a substantial body of work in outcomes research pertaining to lung cancer. Some areas, such as quality-of-life assessment and cost analyses, have received much attention and prominence. Quality-of-care studies, including patient satisfaction, decision making, and doctor-patient communication, appear in publications less often. Unlike other diseases where there are technologies suitable for assessment in several distinct phases of care (screening, primary and adjuvant therapy, follow-up, and survivorship), outcomes research in lung cancer, by virtue of the disease's poor prognosis, is largely focused on palliative care. It is comforting to see that the age, sex, and racial makeup of most studies are similar to those reported for lung cancer in the Surveillance, Epidemiology, and End Results (SEER) Program1(3). It is interesting that race is really only an issue in U.S. studies and is not even noted in studies from other countries. Nevertheless, there remain several areas where further research is needed and where certain vulnerable populations require ongoing vigilance to ensure representation. 1 Editor's note: SEER is a set of geographically defined, population-based, central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research. Quality-of-Life Studies Quality-of-life research in particular has undergone substantial methodological development over the past decade. However, the result is a body of work that has largely included a mixture of tumor stage and histologic types assessed with a wide variety of instruments. Useful clinical information appears to be lacking on the experiences of homogeneous groups of patients receiving specific treatments. The situation is starting to improve, however, as researchers recognize the importance of an intervention's effects on quality of life and move its assessment into the earlier phases of testing. Still, quality-of-life end points rarely figured into the power calculation when designing these trials. This may be appropriate, however, given the relatively low completion rates of quality-of-life surveys discussed below. The EORTC QLQ-C30 is emerging as the most commonly used quality-of-life instrument. This is partly driven by the decision of the MRC to switch from the RSC and HADS to the EORTC scale as a required component of all of its sponsored trials. The EORTC QLQ-C30 has undergone relatively extensive field testing for reliability and validity. Because its first disease-specific module was the lung cancer module, the LC13, much of the early psychometric validation was done in lung cancer patients (44,76-79). Other lung cancer-specific instruments are the FACT-L and the LCSS. All three have undergone fairly extensive reliability and validity testing and appear to have acceptable psychometric properties (5,80). They have never been compared head-to-head, however. All instruments are meant to be self-administered, although the LCSS has an optional observer component. In different studies they were administered in a variety of ways (81), including being sent to physicians to fill out (82), administered by computer (74), or being only partially administered (21,83-86) or scored (38,43). Partial administration was sometimes done in order to focus on the global quality-of-life questions (e.g., questions 29 and 30 of the EORTC QLQ-C30). The use of ad hoc instruments to measure quality of life is decreasing and should continue to be discouraged. The measures described above have undergone extensive field testing, and there is little reason to create new instruments, the results of which are difficult to interpret across studies. The EORTC QLQ-C30 consists of 30 questions in yes/no, Likert, and numerical analogue scale (NAS) formats (87). The yes/no questions have been removed in the most recent version, however. The LC13 adds 13 more questions (88-90). It is estimated to take about 11 minutes to complete (91) and, at the time of this writing, has been translated into 35 languages. The questions are mostly about disease-related symptoms and treatment-related toxicity experienced in the week before the survey. The LC13 is thought to be especially good in situations where patients are relatively ill, but it is lengthy and complicated compared with other instruments. It is unique in including a question about the perceived financial impact of the disease. The FACT-G (92) consists of 34 questions, 28 of which are scored, whereas the FACT-L (93) currently adds seven questions. Questions about hair loss and regret for smoking were taken out in 1995. The FACT-G uses Likert and NAS formats to ask questions about quality of life in the week leading up to its administration. The FACT focuses more on psychosocial dimensions than the EORTC instrument. Consequently, it may be best in situations where patients are not as sick. It has been assessed at a grade 6-7 reading level, and it has been translated into at least 30 languages. Taking up to 10 minutes to administer, it is also a fairly burdensome scale to complete. As a result, the Physical and Functional scales have been combined with the lung cancer module to form the shorter 21 item “Trial Outcome Index” (94,95). The LCSS is only a disease-specific instrument, with no general health component (96-100). It focuses exclusively on the symptoms of lung cancer and does not attempt to assess the toxicity of treatment. Its advantage is its simplicity. It is rated at a grade 2 level of comprehension; consists of only nine visual analogue scales (VAS) (and six optional ones for an observer to fill out), asking about quality of life in the previous 24 hours; and takes only 5-8 minutes to complete (101). However, the lack of a general component makes it difficult to compare across disease sites, and some respondents have difficulty using the VAS. It is recommended that it be given initially as a face-to-face interview to demonstrate the VAS. It has been translated into at least 26 languages (102). Additional Observations Missing data continue to be a big problem in quality-of-life research. This is especially true in lung cancer, because patients are often too sick to complete surveys and usually experience a rapid downhill course (19). The effects of aggressive treatment can contribute to this phenomenon as well. Consequently, censoring is informative, resulting in misleading analyses in which the average quality of life can appear to increase over time as only healthier patients remain. Several studies in this review (22,24,33,35-43) found that only about one-half of the patients had more than a baseline evaluation, making repeated measures analyses and even comparisons of the proportion of patients who improved versus worsened impossible. Some analysts have tried to impute missing data (19), but this is difficult when there is only one measurement from a patient and the specific trajectory of quality of life is uncertain. Others have tried to limit the analysis to those with complete data (36); however, this may not be valid because it assumes uninformative censoring. As a result, some have turned to looking at other measures such as performance status (90) to estimate missing quality-of-life data. Methodological studies developing less burdensome instruments or validating the use of proxy respondents in various situations would be welcome in order to ameliorate the problem of missing data as a result of patient deterioration in lung cancer quality-of-life studies. Because of the short survival of lung cancer patients, the handling of death presents another analytic challenge. Quality of life can be assessed at a fixed time point or at the time of median survival, but this will lead to overestimates because the patients who die before that time, and who most likely had a worse quality of life, will not be included. Some have calculated an area under the survival curve, adjusted for quality of life, to come up with an average daily quality-of-life estimate (19). For example, the Q-TWiST approach assigns death a value of 0 (103,104). However, patients have rated some health states pertinent to lung cancer, such as having constant pain, as being worse than death (105). Cost Studies The number of economic studies peaked in the middle of the decade with the introduction of several new and exciting, though expensive, interventions like multimodality therapy for stages IIIA or IIIB disease and palliative compounds like gemcitabine and paclitaxel. Because there were fewer changes in the management of SCLC, it received less attention. Recent clinical data on the possible effectiveness of expensive technologies such as spiral computed tomography and positron emission tomography scanning in the early detection and staging of lung cancer will probably result in another run of publications in the next few years. The finding in most reports that the study intervention is cost-effective is likely the result of a combination of factors, some benign and some more problematic. Most cost-effectiveness studies probably start with a “back of the envelope” calculations that can tell roughly whether the analysis being considered is likely to yield an important result; those interventions that are not cost-effective are not pursued. Furthermore, negative studies are generally less interesting and are less likely to be submitted or accepted for publication (“publication bias”). However, the wide variation in methodologies reported may also have an effect. Reporting, for example, cost-effectiveness without considering the cost of the drug under evaluation (59-61) could present an inaccurate picture. Publication of methodological and reporting standards by the U.S. Panel on Cost-Effectiveness in 1996 and demands for transparency in published economic models should lead to improvement in the general methodological quality and comparability of studies in the future. Another positive effect should be more focus on the societal, patient, and caregiver costs of undergoing treatment, areas that have received little attention to date. Other Issues Quality of care is an area receiving increasing attention in other areas of medicine, yet few studies have analyzed the quality of lung cancer care. In addition to studies attempting to shine a light on inequities and variation in practice, more research is needed in the areas of patient satisfaction, decision making, communication, and the appropriate use of palliative interventions. Related to this, there seems to have been little qualitative research done to date in lung cancer, compared with other diseases such as breast cancer. Qualitative methods may be able to bring more insight into patients' actual experience of this terrible disease and its treatment. Despite good representation in lung cancer outcomes research, at least in U.S. studies, visible minority patients, the elderly, and women remain at risk for being relatively neglected. Lung cancer is a disease of the elderly and is more common in several minority groups, such as African Americans. Furthermore, lung cancer is increasing in women, whereas the incidence in men has leveled off and has begun to decrease. By addressing the effects of socioeconomic status, literacy, and culture among these groups of patients, outcomes researchers have the opportunity to explore issues of equity and justice in these patients' access to care and the quality of care they receive. Outcomes research, encompassing such elements of health services research as cost-effectiveness analyses and quality-of-life studies, studies looking at nontraditional clinical end points like quality of care and satisfaction, as well as disease modeling and decision analytic studies, is currently represented in all of these facets in the lung cancer literature. There needs to be more agreement on consistent methods, preferred instruments, and consideration of these outcomes early on in the study design, however, in order to increase rigor in the field. For example, including utility estimates in cost-effectiveness analyses is particularly important for most lung cancer interventions, because effects on quality of life must be balanced against what are usually modest benefits from treatment. In the end, the greatest gains will likely come from exploring the relationships among traditional biomedical outcomes like response and survival, symptom measures, functional status scales, and nontraditional outcomes like health-related quality-of-life and satisfaction with care in order to determine in which situations there is sufficient value added to justify expending the resources to gather these additional data. Appendix —Evidence* Reference No.   Year   Design   Intervention   Measure 1   Measure 2   Measure 3   Outcome   n   Age, y   F   Nonwhite   Histology   Stage   Result   *ACE = doxorubicin (Adriamycin), cyclophosphamide, and etoposide; ATP = adenosine 5′ -triphosphate; AUC = area under the curve; bronch = bronchoscopy; BSC = best supportive care; bx = biopsy; CAP = cyclophosphamide, doxorubicin, and cisplatin; Carbo = carboplatin; CARES-SF = Cancer Rehabilitation Evaluation System—Short Form; CAV = cyclophosphamide, doxorubicin (Adriamycin), and vincristine; CDI = Clinical Dyspnea Index; CEA = cost-effectiveness analysis; CHART = continuous hyperfractionated accelerated radiation therapy; chemo = chemotherapy; CMA = cost-minimization analysis; CODE = cisplatin, vincristine, doxorubicin, and etoposide; CT = computed tomography; CUA = cost-utility analysis; cyclo = cyclophosphamide; DA = decision analysis; EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; EP = etoposide plus cisplatin; EUS = endoscopic ultrasound; F = proportion of females in the study sample; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module; FDG = fluorodeoxyglucose; FLIC = Functional Living Index—Cancer; FNA = fine-needle aspiration; fx = fractions of radiotherapy; G-CSF = granulocyte colony-stimulating factor; Gem = gemcitabine; H = Hounsfield units; HADS = Hospital Anxiety and Depression Scale; HUI = Health Utility Index; I = ifosphamide; IA = ifosphamide plus doxorubicin (Adriamycin); ICE = ifosphamide, carboplatin, and etoposide; IEP = ifosphamide, epirubicin, and cisplatin; IV = intravenous; LASA = Linear Analogue Self-Assessment; LC = lung cancer; LCSS = Lung Cancer Symptom Scale; LOS = length of stay; M = mitomycin C; MD = physicians; mede = mediastinoscopy; MIP = mitomycin, ifosphamide, and cisplatin; MRC = British Medical Research Council; MVP = mitomycin, vinblastine, and cisplatin; n = sample size; NSCLC = non-small-cell lung cancer; NVB = vinorelbine; P = cisplatin; PAIS = Psychosocial Adjustment to Illness Scale; PC = prospective cohort; PCI = prophylactic cranial irradiation; PET = positron emission tomography; Ph = phase; po = oral; POMS = Profile of Mood States; PR = partial tumor response; PRQ = Personal Resource Questionnaire; PRUI = Pneumoconiosis Research Unit Index; QLCL-E4 = Quality of Life Checklist—Enjoyment, Four Questions; QLI = Quality of Life Index; QoL = quality of life; RC = retrospective cohort; RCT = randomized controlled trial; RR = response rate; RSC = Rotterdam Symptom Checklist; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SCL-90 = Symptom Checklist—90; SCLC = small-cell lung cancer; SIP = Sickness Impact Profile; SSQ = Subjective Significance Questionnaire; STAI = State-Trait Anxiety Inventory; Taxol = paclitaxel; SUPPORT = Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments; UNC = University of North Carolina; VATS = video-assisted thoracoscopy; VBL = vinblastine; VDS = vindesine; VNSSL = video-assisted non-rib spreading lobectomy; VP = vindesine and cisplatin; VP-16 = etoposide; YAG = yttrium laser.   (22)  1999   RCT   NVB vs. BSC   EORTC QLQ-C30   EORTC LC13     Qol   154   > 70   13     NSCLC   IIIB and IV   Stopped early because of poor accrual. NVB increased survival and overall QoL   (106)  1998   RCT   CHART vs. conventional RT   RSC   HADS     QoL   356   65   23     NSCLC   I-IIIB   Transient esophagitis with CHART, but otherwise similar QoL   (81)  1998   PC   RT (CHART, conventional)   RSC   HADS     QoL   2300   65   23     Both   I-IIIB   More consistency when instruments administered by trained staff   (40)  1998   RCT   Taxol-P vs. teniposide-P   EORTC QLQ-C30   EORTC LC13     QoL   317   59   30     NSCLC   IIIA-IV   Taxol better at 6 wk; effect lost at 12 wk   (107)  1998   PC   CAV/EP vs. CODE   EORTC QLQ-C30   SSQ     QoL   111   58       SCLC   Extensive   SSQ used to define small, moderate, or large changes in the EORTC QLQ-C30   (108)  1997   RCT   CAV/EP vs. po VP-16   RSC   MRC daily diary card     QoL   155   67   46     SCLC   All   po VP-16 had inferior survival and QoL   (109)  1996   RCT   EP +/- megace   LASA       QoL   252     40     SCLC   Extensive   Megace resulted in decreased response and survival, similar QoL   (110)  1994   RCT   EP +/- hydrazine   FLIC       QoL   237     32     NSCLC   IIIB and IV   Survival trend worse with hydrazine, similar QoL   (24)  1994   RCT   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Survival similar with hydrazine, but QoL worse (e.g., neutropenia)   (111)  1999   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Pain predicted survival better than did overall QoL   (90)  1997   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Although it did not change the outcome of the trial, QoL assessment added understanding of the patients' perspective on toxicity, etc.   (41)  1999   Ph II   96-h Taxol   FACT-G   FACT-L     QoL   13   56   61     NSCLC   IIIB and IV   Only 3 of 13 patients were able to complete 3 questionnaires because of progressive disease   (42)  1998   Ph II   MVP   EORTC QLQ-C30   EORTC LC13     QoL   50   66   34     SCLC   All   QoL improved from baseline   (78)  1994   PC   Megace   EORTC QLQ-C30   QLCL-E4 (enjoyment)     QoL   20         NSCLC     Fatigue, appetite, among others, correlate better with overall QoL than does weight gain   (82)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30       QoL   100         NSCLC   I-IIIB   Only 34% completed questionnaires. QoL better with lobectomy than with pneumonectomy   (54)  1997   PC   RT for NSCLC   RSC   HADS     QoL   98         NSCLC     Used factor analysis to map RSC and HADS onto EuroQoL and HUI for utility determination   (112)  1996   PC   chemo   Holmes QoL checklist   STA1     QoL   50   58       NSCLC   IIIA-IV   Anxiety levels and personality type correlate with QoL effects   (79)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30   Spitzer Index     QoL   52   52   27     NSCLC     QoL is restored 3-6 mo after surgery   (113)  1998   Ph II   ICE   MRC daily diary card       QoL   30   60   57     SCLC   All   QoL satisfactory, but worse on the first day of each cycle   (19)  1997   PC   chemo   LCSS       QoL   673   61   32     NSCLC   IIIA-IV   Frequent QoL measurements are needed, and AUC may be useful   (43)  1998   RCT   Carbo + VP-16   EORTC QLQ-C30   EORTC LC13     QoL   150   64   41     NSCLC   IIIB and IV   The chemotherapy resulted in improved survival and QoL   (23)  1998   Ph I   Carbo + po VP-16   LCSS       QoL   46   > 70   15     NSCLC   IIIB and IV   QoL improved in 41% and was a better predictor of survival than was response   (83)  1997   RC   RT for NSCLC   LCSS       QoL   63   67   15     NSCLC   All   RT appears to have improved QoL   (26)  1997   Ph II   Taxol by 3-h infusion   FACT-G   FACT-L     QoL   20   63   45     NSCLC   IV   Baseline QoL predicted response, but changes in QoL did not correlate with response   (20)  1997   Ph II   3-h Taxol + Carbo   FACT-G   FACT-L     QoL   11   65   0   27   NSCLC   IIIA-IV   QoL improved in most patients   (114)  1997   Randomized Ph II   Carbo + Taxol 175 vs. 225 mg/m2  EORTC QLQ-C30       QoL   49   61   14     NSCLC   IIIA-IV   No difference in QoL   (115)  1997   Ph II   Taxol by 3-h infusion   RSC   HADS     QoL   21   55   25     NSCLC   IIIA-IV   Treatment well tolerated. High completion rate for QoL forms   (21)  1996   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Patients with poor prognostic features had worse QoL at baseline, but more improvement with chemo   (35)  1992   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Mean compliance 49%. Institution strongly predicted compliance   (27)  1995   PC   Usual care   Likert Symptom Scale       QoL   82   64   39     Both   All   Increased symptom distress with advanced disease, young age, and women. QoL predicted survival   (84)  1995   RCT   CAV vs. Carbo + teniposide   EORTC QLQ-C30       QoL   59   58   8     SCLC   Extensive   CAV yielded better survival, equal QoL   (116)  1995   RCT   Weekly EP/IA vs. 3 weekly EP/CAV   MRC daily diary card       QoL   75   62   36     SCLC   All   No difference in survival. QoL better on 3-weekly treatment (every 3 wk)   (117)  1994   PC   Usual care   Hassles Scale   Demands of Illness Inventory   PRQ, PAIS   QoL   56   60   38   16   Both   IIIA-IV   Black patients and patients with more demands of illness had worse psychosocial adjustment   (118)  1994   Ph II   Fotemustine   Spitzer Index       QoL   77   60   14     NSCLC   All   17% RR. QoL stable   (98)  1994   PC   Usual care   LCSS       QoL   207         NSCLC   All   LCSS was feasible, reliable, and valid   (76)  1993   PC   Usual care   EORTC QLQ-C30       QoL   305   63   24     Both   All   EORTC QLQ-C30 was feasible, reliable, and valid   (96)  1993   PC   Usual care   LCSS       QoL   121   59   33     Both   All   LCSS was feasible, reliable, and valid   (119)  1996   PC   Usual care   Interviews       QoL   200   66   44     Both   All   Family life, health, and social life were most important to patients. Family and social life are missed by most QoL instruments   (15)  1993   PC   Usual care   Symptom Distress Scale   CARES-SF     QoL   69   61   100     Both   All   Pain, fatigue, and insomnia were strongly correlated in women with LC   (120)  1992   Cross-section   Usual care   Spiritual Health Inventory       QoL   23     30   8   Both   All   Patients had moderately high levels of spiritual health, but nurses were poorly able to determine this   (25)  1991   RCT   Planned vs. “as required” chemo   MRC daily diary card       QoL   300   65   25     SCLC   All   Survival similar, but patients with planned treatment had better QoL   (18)  1991   PC   Palliative RT   EORTC QLQ-C30   MRC General Condition Scale   MRC Dyspnea Grade   QoL   40   68   18     NSCLC   IIIA-IV   MDs were poor at predicting QoL but were good at detecting changes   (121)  1991   RCT   Maintenance chemo vs. none after 6 mo   MRC daily diary card       QoL   369         SCLC   Limited   Similar survival, better QoL with maintenance chemo   (28)  1991   PC   Usual care   FLIC       QoL   40   62   13   38   NSCLC   IV   QoL predicts survival   (44)  1990   RCT   PCI   MRC daily diary card   EORTC QLQ-C30   Spitzer Index   QoL   53   63   30     SCLC   All   Diaries are reliable and valid. QoL worsens with successive chemo and PCI   (122)  1990   Ph I/II   Cyclo + trimetrexate   LASA       QoL   55   58   1     NSCLC   All   Testing of 9 domains feasible. Stable QoL despite only 4% PR   (123)  1997   Cross-section   Usual care   SF-36       QoL   590   72   48     Both   All   Also had lung, colon, and prostate cancer patients: LC patients were the most debilitated   (124)  1993   Cross-section   Usual care   Interviews   PAIS     QoL   61   60   33   14   Both   All   No relationship between perceived control and psychosocial adjustment   (29)  1994   PC   Various   FLIC       QoL   438         Both   All   QoL predicts survival   (91)  1996   PC   chemo   EORTC QLQ-C30       QoL   305         Both   All   Mixed response of QoL parameters to chemo   (125)  1996   RCT   2 vs. 13 fx   RSC   HADS   MRC daily diary card   QoL   509   66   21     NSCLC   Unresectable   2 fx palliated symptoms faster, but 13 fx had better survival   (88)  1994   PC   Various   EORTC QLQ-C30   EORTC LC13     QoL   883         Both   All   Neuropathy, dyspnea, and pain sections of the instrument need further refinement   (17)  1997   PC   Usual care   Symptom Distress Scale       QoL   60   58   100   13   Both   All   Factor analysis found several clusters of distress   (126)  1994   PC   Thoracotomy   QLI   SIP   CDI, PRUI   QoL   91   63   31     NSCLC   Resectable   QoL deteriorates during the first 3 mo after surgery but improves afterward   (85)  1998   PC   Diagnosis of LC   HADS   EORTC QLQ-C30     QoL   129   68   40     Both   All   Anxiety decreases after the diagnosis of LC has been made   (127)  1994   RCT   RT to primary tumor   POMS   Clinician-completed rating scale   Trail Making B Test   QoL   119   59   33   7   SCLC   Limited   RT improved survival but decreased QoL and distress   (16)  1993   PC   Usual care   CARES-SF   Symptom Distress Scale     QoL   69   61   100   14   Both   All   QoL was predicted most by symptom distress, physical functioning, and recurrence   (31)  1995   PC   Usual care   HADS   RSC   Spitzer Index   QoL   40   60   20     Both   All   Brief QoL scales correlated well with these formal measures, but not with overall QoL   (128)  1992   PC   chemo   Cancer Inventory of Problem Situations       QoL   36   66   19     SCLC   All   QoL improved with chemo   (33)  1991   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   Improvement on the QoL scales correlated with response to treatment   (89)  1992   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   The EORTC questionnaire performed well, except for emotional and social functioning   (129)  1998   RCT   IEP vs. MVP vs. BSC   FLIC   QLI     QoL   107   57       NSCLC   IV   The chemo resulted in improved survival, without a decrease in QoL   (130)  1993   PC   Usual care   Symptom checklist       QoL           Both   All   Checklists draw attention to problems and can be followed over time   (131)  1992   Cross-section   Usual care   Interviews       QoL   30   61   50     Both   All   Caregivers can serve as proxies for patients, but they tend to underestimate physical function   (132)  1992   Cross-section   Usual care   FLIC   Investigator-designed questionnaire     QoL   64   61   23     Both   All   Good reliability and validity for Japanese translation of the FLIC. Cancer patients scored lower than 50 noncancer patients, especially in mood, anxiety, relationships, and physical function   (133)  1999   PC   Usual care   Investigator-developed diary   LASA     QoL   53   62   17     Both   II-IV   Japanese diary form was reliable and valid   (134)  1995   PC   BSC vs. IEP vs. MVP   FLIC   QLI     QoL   118   56   30     NSCLC   IIIB and IV   Thai modifications (T-FLIC and T-QLI) correlated well with each other and Karnofsky performance status   (30)  1998   Ph II   MIP   LASA       QoL   38   38   21     NSCLC   IIIB and IV   39% RR; 58% improved QoL. QoL predicted survival   (135)  1996   PC   Usual care   Locus of control   Symptom checklist     QoL   31   58   13     Both   All   Patients have a more internal locus of control than non-cancer patients. Locus of control and QoL were not related   (136)  1996   Case-control   Usual care   Nottingham Health Profile   EORTC QLQ-C30   EORTC LC13   QoL   232   66   44     Both   All   Interviewer-administered QoL instruments were acceptable and even enjoyable to most patients   (99)  1999   PC   chemo   LCSS       QoL   673   59   32   17   NSCLC   IIIA-IV   Normative scores for this population are presented   (94)  1995   PC   Usual care   FACT-G   FACT-L     QoL   116   60   53   25   Both   All   Test-retest reliability is demonstrated   (32)  1995   PC   Usual care   Therapy Impact Questionnaire       QoL   128   64   7     Both   All   Patient perception of QoL predicted survival   (137)  1994   Cross-section   Usual care   CARES-SF   LASA     QoL   57   62   44   7   Both   Survivors   LC survivors have poorer QoL than colon or prostate cancer survivors   (77)  1994   PC   chemo   EORTC QLQ-C30       QoL   160   58       Both   All   The instrument is sensitive to the effects of chemo administration and tumor stage   (36)  1994   RCT   chemo   RSC   HADS     QoL   310     37     SCLC   All   Explored ways of dealing with attrition and missing information   (97)  1994   PC   chemo   LCSS   Brief Symptom Inventory   SCL-90, POMS, SIP   QoL   144   59       NSCLC   IIIA-IV   Confirmed construct validity   (138)  1993   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   127         SCLC   All   Fatigue and malaise are important predictors of QoL   (139)  2000   Cross-section   PET vs. mede for staging   Numerical rating scale       QoL   23   57       NSCLC   All   Patients prefer noninvasive staging. Disease extent is the major determinant of utility   (140)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   Clinical benefit     QoL   207   59   18     NSCLC   IIIB and IV   Survival favored docetaxel. Nausea, pain, and dyspnea improved with docetaxel, with a trend toward improved global QoL   (141)  1999   RCT   Gem vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   147   59   23     NSCLC   IIIA-IV   No difference between arms in survival or QoL, although less toxicity in Gem arm   (142)  2000   PC   None   Symptom Distress Scale   Thurstone scale     QoL   26   66   50     Both   All   Fatigue was the most intense symptom, but it ranked second last on the Thurstone scale   (143)  1999   PC   None   Freiburg Questionnaire of Coping With Illness   A uniquely developed Depression Scale   QoL   103   59   17       Both   All   Depressive coping and emotional distress correlate with shorter survival   (37)  1999   Ph II   Gem   EORTC QLQ-C30   EORTC LC13     QoL   30   59   10     NSCLC   IIIB and IV   20% RR. Cough was the only aspect of QoL that changed substantially, improving after 3 cycles   (144)  2000   PC   Palliative RT   EORTC QLQ-C30   EORTC LC13     QoL   69         NSCLC   All   QoL, especially dyspnea and social functioning, improved in those with objective tumor response   (145)  2000   PC   High-dose palliative RT   EORTC QLQ-C30       QoL   42   70       Both   All   Patients had improved QoL after treatment. Regression models were fitted on the basis of both time since treatment and time left to live   (146)  2000   Ph I/II   High-dose EP   EORTC QLQ-C30   EORTC LC13     QoL   42   57   22     NSCLC   IIIA-IV   RR of 33%. QoL stable, with improved emotional status but worsening fatigue   (147)  2000   RCT   Gem vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   300   65   37     NSCLC   IIIA-IV   QoL was the main end point. Pain, cough, and fatigue all improved > 10%. There was no difference in survival. 19% PR   (38)  2000   Ph II   Gem + NVB   EORTC QLQ-C30   EORTC LC13     QoL   126   63   12     NSCLC   IIIB and IV   Dropout was a big problem   (39)  2000   Ph II   NVB   Therapy Impact Questionnaire       QoL   46   75   13     NSCLC   All   After baseline, large amounts of missing data. Patients often required help to complete questionnaires. QoL stable throughout treatment   (148)  2000   Ph II   Taxol-ifosphamide-P   LCSS       QoL   50   58   12     NSCLC   IIIA-IV   64% tumor RR. QoL improved in 74%   (149)  1999   PC   Informed consent   HADS       QoL   119   65   36     NSCLC   All   Informed consent increases anxiety and depression, especially in women and patients with poor performance status   (34)  2000   PC   RT   EORTC QLQ-C30   EORTC LC13     QoL   198     15     NSCLC   I-IIIB   Global QoL predicts survival for lymph node-positive patients   (150)  2000   PC   Usual care   SF-36   Symptom Experience Scale     QoL   129   72   42   5   Both   All   Younger patients, patients with higher previous physical function, and patients with more current symptoms experienced greater loss of function   (151)  1999   PC   RT   Quality adjusted survival time       QoL   979         NSCLC   II-IIIB   Two authors chose weights for different toxic effects and calculated Q time for different therapies based on prior RTOG studies   (152)  2000   RCT   Taxol vs. BSC   RSC       QoL   157   64   25     NSCLC   IIIB and IV   Functional ability improved with Taxol. Otherwise, no difference   (153)  2000   RCT   ATP vs. BSC   RSC       QoL   58   62   35     NSCLC   IIIB and IV   QoL deteriorated in the control group but not in the ATP group   (154)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   RSC     QoL   104   61   31     NSCLC   IIIB and IV   QoL will be reported separately: less worsening in docetaxel arm   (155)  2000   PC   Usual care   HADS   RSC     QoL   1189         Both   Advanced   Depression more common in SCLC patients, among women, and in more debilitated patients   (95)  2000   RCT   Taxol-P vs. EP   FACT-G   FACT-L     QoL   599   62   36   13   NSCLC   IIIB and IV   Trend toward improved QoL on the Taxol arm   (156)  2000   RCT   ACE every 2 wk with G-CSF vs. ACE every 3 wk   RSC       QoL   403   61   42     SCLC   All   Survival was improved with similar QoL in the intensively treated patients   (157)  1999   RCT   Gem-P vs. MIP   EORTC QLQ-C30   EORTC LC13     QoL   307   61   24     NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR with similar QoL, survival, and time to disease progression   (86)  1999   RCT   MIP vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   820   64   25     NSCLC   IIIA-IV   MIP improved survival with improved QoL   (158)  1999   RCT   Gem-P vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   135   59   7   1   NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR and delayed disease progression; QoL was similar   (159)  2000   RCT   Gem-NVB vs. NVB   LCSS       QoL   120   75   6     NSCLC   IIIB and IV   Gem-NVB improved survival and time to symptomatic progression; only 40% had a decrease in QoL compared with 60% receiving NVB alone   (160)  1999   PC   VATS vs. open thoracotomy   Symptom questionnaire (unique)       QoL   44   62   36     NSCLC   Resectable   VATS resulted in decreased pain and increased satisfaction with the wound   (161)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CEA       Cost     51       Both   All   Open bx is most cost-effective   (45)  1993   RC   Restage responding patients with scans or bronch   CEA       Cost   324   62   45     SCLC   Limited   Restaging is not cost-effective   (162)  1996   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (163)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (164)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (165)  1993   RC   VATS vs. open thoracotomy   CMA       Cost   150   63   57     NSCLC   All   Trend toward decreased operating time and LOS for VATS despite higher equipment costs   (166)  1997   DA   FNA for patients with a history of cancer   CEA       Cost           Both   All   FNA with selected use of thoracoscopy is most cost-effective   (167)  1995   RCT   CT vs. mede   CEA       Cost   685   64   29     NSCLC   Resectable   CT is more cost-effective than mede   (46)  1995   DA   Head CT for staging disease in patients with no neurologic symptoms   CEA       Cost           Both   All   CT head is not cost-effective   (168)  1996   DA   Cytologic brushings for bronchoscopically visible tumors   CEA       Cost           NSCLC   All   Either washings or brushings, but not both, are cost-effective   (53)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CUA       Cost           Both   All   For patients averse to waiting, thoracoscopy is most cost-effective; for those averse to morbidity, expectant waiting is best   (169)  1993   RC   Sequence of staging tests   CMA       Cost   451         SCLC   All   The algorithm can save one-third of costs as long as testing is stopped as soon as metastases are detected   (170)  1998   DA   Diagnosis of LC   CEA       Cost           Both   All   Open bx is most cost-effective in operative candidates; sputum is least   (47)  1998   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Routine use of G-CSF is not cost-effective   (171)  1999   DA   Radon screening and mitigation to prevent LC   CEA       Cost           Both   All   Limiting testing to high-risk geographical areas and requiring a confirmatory test before mitigation are most cost-effective   (172)  1999   RC   Usual care   Cost       Cost   253   71       Both   All   Costs were less than those for Canadian studies because of less aggressive intervention   (173)  1994   RC   Usual care   Cost       Cost   300         Both   All   A “top-down” cost allocation approach is feasible   (174)  1993   RCT   G-CSF during chemo   CMA       Cost   68         SCLC   All   G-CSF could save money in patients at high risk of febrile neutropenia   (48)  1996   DA   Follow-up after curative resection   CMA       Cost           NSCLC   All   There was a fivefold difference in the cost of follow-up strategies, with no evidence of difference in benefit   (175)  1991   RC   Usual care   Cost       Cost   15 381   > 65       Both   All   LC cost $12 510 1984 U.S. dollars   (176)  1996   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost           NSCLC   IIIB and IV   NVB-P was effective and cost-effective   (49)  1999   DA   Conformal vs. standard RT   CMA       Cost           Both   All   Conformal RT was twice as expensive as standard   (177)  1990   PC   chemo   Hospital days       Cost   90     25     SCLC   All   Average 18 days in hospital: 69% of hospital days due to tumor complications   (59)  1996   PC   Gem vs. VP-P vs. VP-I   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (60)  1996   PC   Gem vs. VP-P   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (178)  1995   DA   Gem vs. VP-I   CMA       Cost           NSCLC   IIIA-IV   Excluding drug costs. Gem used fewer resources   (179)  1996   RC   P + either VP-16 or VP-16 phosphate   CMA       Cost   254         SCLC   All   VP-16 phosphate, a prodrug of VP-16 with shorter administration time, consumes fewer resources   (180)  1997   DA   Multimodality treatment   CEA       Cost           NSCLC   III   Multimodality therapy is cost-effective   (181)  1997   DA   Taxol vs. BSC   CEA       Cost           NSCLC   IV   Taxol is cost-effective   (182)  1999   DA   Taxol-P vs. BSC   CEA       Cost           NSCLC   IV   Taxol-P is cost-effective   (183)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (184)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (185)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (186)  1996   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (187)  1993   RC   chemo   CMA       Cost           SCLC   All   Large variation in the cost of regimes with similar efficacy   (188)  1996   DA   NVB vs. NVB-P vs. VP-16-P vs. VBL-P vs. BSC   CEA       Cost           NSCLC   IV   VBL-P is most cost-effective, but NVB-P is most effective and is cost-effective when given in an outpatient setting   (189)  1996   DA   Gem vs. BSC   CEA       Cost           NSCLC   IV   Gem is more costly but is still cost-effective   (190)  1998   RC   Usual care   Cost       Cost   336   <65       NSCLC   All   Type of treatment predicted total cost more than did hospital days   (191)  1990   RCT   CAP vs. VP vs. BSC   CEA       Cost   137         NSCLC   IIIB and IV   The chemo was both effective and cost-effective. In fact, CAP actually saved money   (50)  1995   RCT   CAP vs. VP vs. BSC   CUA       Cost   137         NSCLC   IIIB and IV   Did not confirm the cost-savings found by Jaakkimainen et al. (65) but did find chemo to be cost-effective   (51)  1994   RC   G-CSF during chemo   CMA       Cost   137   62   47     SCLC   All   G-CSF was not cost-effective   (192)  1996   DA   Gem-P vs. NVB-P vs. VP-16-P vs. MIP   CEA       Cost           NSCLC   IIIB and IV   Gem-P had the lowest cost per response   (193)  1992   RC   Usual care   Cost       Cost   39   68       SCLC   All   Hospitalization and chemo drug costs were the main drivers of SCLC costs. QoL did not suffer with intensive chemo   (194)  1995   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost   612         NSCLC   IIIA-IV   As long as NVB's toxicity profile is acceptable, it is effective and cost-effective   (195)  1996   RCT   M-NVB-P vs. M-VDS-P   CEA       Cost   209   61   5     NSCLC   IIIA-IV   M-NVB-P costs less per response   (55)  1997   RCT   CHART vs. conventional RT   CEA       Cost   284   65   21     NSCLC   I-IIIB   CHART more costly but likely cost-effective, given the survival benefits   (56)  1998   DA   Gem vs. EP vs. IE   CMA       Cost           NSCLC   IIIB and IV   Gem cost-saving   (196)  1996   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Based on a meta-analysis showing no survival benefit but reduced incidence of neutropenic fever, G-CSF would have to cost $395-$569 per cycle to be cost neutral   (197)  1992   RCT   po vs. IV VP-16 with P   CMA       Cost   83         SCLC   All   The oral regimen was less costly and equally efficacious   (198)  1995   Ph II   Fazarabine   CMA       Cost   23   65   39     NSCLC   IV   Fazarabine had no activity (0% RR) and similar costs to VP-16-P   (199)  1998   RC   Usual care   Cost       Cost   554   <65   43     Both   All   Hospital charges ≈$35 000 in the last year of life   (200)  1998   RC   VATS vs. open thoracotomy   Cost       Cost   80   56   33     NSCLC   I   VATS wedge resection was less costly, but VATS lobectomy was more costly than the open procedure   (201)  2000   Cross-section   PET added to staging work-up   Questionnaire       Cost   87   55   16     Both   All   Willingness to pay for PET ranged from $1500 to $4000, proportional to perceived risk of cancer and income. Insured vs. Medicaid willing to pay more   (202)  2000   RC   Ph II chemo trials   Cost       Cost   43         Both   IV   The cost of doing Ph II studies is more for a drug that works, as it is given longer, and is driven by imaging studies and laboratory tests. The cost was still less than standard therapy   (203)  2000   RCT   Gem-P vs. VP-16-P   Cost       Cost   135   58   7     NSCLC   IV   Survival was equivalent, although RR and time to progression were superior for Gem-P. Increased cost of the drugs was offset by decreased hospitalization   (62)  2000   RCT   YAG vs. YAG + brachytherapy         Cost   29   61   21     NSCLC   All   Brachytherapy saved money by decreasing the need for repeat procedures. No method described   (52)  2000   DA   Adding PET to chest CT         Cost   56         NSCLC   All   PET unlikely to be a cost-effective addition to the diagnostic work-up in Japan (although it seems to easily meet U.S. standards of cost-effectiveness)   (63)  1999   Case series   VNSSL   Cost       Cost   250     52     Both   Resectable   VNSSL appears efficacious, costs ≈50% of open thoracotomy. No method described   (204)  1999   RCT   Taxol-P vs. teniposide-P   Cost       Cost   62         NSCLC   IV   Taxol-P had a higher RR, at a cost of $21 011 per response   (205)  2000   RC   Follow-up after curative resection   Survival   Cost     Cost   245   64   41     NSCLC   I and II   Most recurrences are found by the family doctor and have equivalent survival to that found by the surgeon. Costs would be 75% less if family doctors did all follow-up, and the results the same   (206)  2000   RCT   Pleural tent after lobectomy   Cost       Cost   50   67   20     NSCLC   Resectable   Pleural tenting reduced air leak, hospital days, and costs   (207)  1999   RC   Staging for early-stage disease   Cost       Cost   755   63   39     NSCLC   I   Metastases were found in only 2.1% of T1N0 and 5.4% of T2N0 tumors. Total cost of unnecessary tests was $924 168   (208)  2000   RCT   CT scan before bronch   Cost       Cost   171   67   38     NSCLC   Resectable   CT averted many invasive procedures, resulting in a lower cost per patient   (209)  1999   DA   EUS/FNA vs. mede   Cost       Cost           NSCLC   Resectable   Despite a lower negative predictive value, EUS was less costly   (57)  1999   DA   Radon screening and mitigation   Cost       Cost           Both   All   Radon remediation is cost-effective from all perspectives in preventing LC   (64)  2000   Case series   Accelerated hyperfractionation   Medicare schedule       Cost   29   68   41     NSCLC   IB-IIIB   Costs only presented in “Discussion” section. Tolerated well, and costs not excessive compared with conventional treatment   (210)  2000   DA   chemo   Cost       Cost           NSCLC   IV   NVB-P is the most cost-effective regimen at conventional thresholds of cost-effectiveness. Gem is most cost-effective when QoL is considered   (58)  2000   DA   Imaging and bx strategies to work up adrenal masses   Cost       Cost           NSCLC   Resectable   Unenhanced CT using a 10 H threshold, followed by magnetic resonance imaging if needed, was the most cost-effective strategy   (211)  1999   RC   Transbronchial needle aspiration   Cost       Cost   99         Both   Resectable   No economic methods given; $27 335 in subsequent procedures estimated to be averted   (70)  1998   RC   Bronch   Record audit   Survey     Quality   2238         Both   All   Variation in histologic distributions may be due to pathologic interpretation   (212)  1998   RC   Usual care   Record audit       Quality   1142   34       Both   All   Median time from first contact to management decision was 18 days; however, time to surgery was 63 days and time to RT was 70 days   (66)  1996   RC   Usual care   Record audit       Quality   312   65   33     SCLC   All   Elderly patients were more likely to get suboptimal care   (71)  1996   PC   Usual care         Quality   622   68   33     Both   All   Substantial variation in referral patterns, diagnostic work-up, and management   (67)  1995   RC   Usual care         Quality   5205   > 65   31   19   NSCLC   All   The elderly are less likely to be treated by all modalities at all stages   (213)  1997   RC   Usual care   Record audit       Quality   107         NSCLC   All   Overuse of testing. Otherwise good compliance with guidelines   (72)  2000   RC   chemo   Administrative data       Quality   6308   74   37   16   NSCLC   IV   Substantial unexplained variation in the use of chemo based on race, geography, and socioeconomic status   (214)  2000   Cross-section           Quality   868   69   30     NSCLC   All   Describes the proportion of patients treated in different ways   (68)  2000   PC           Quality   2182   61   42   18   NSCLC   IV   SUPPORT: older patients get less care   (73)  2000   Cross-section     Survey       Quality   9200         NSCLC   All   Medical oncologists more likely than radiation oncologists to recommend combined modality therapy for stage III disease, emphasizing the importance of multidisciplinary decision making   (69)  1999   RC   Surgery   Administrative data       Quality   10 984   > 65   32   8   NSCLC   I and II   Black patients less likely than white patients to undergo surgery, resulting in inferior survival   (74)  2000   Non-RCT   Computerized QoL surveys in clinic   EORTC QLC-C30   Patient Satisfaction Questionnaire     Satisfaction   53   65   10     Both   All   QoL surveys resulted in more symptoms being addressed. Satisfaction was high and similar in both groups   (75)  1999   PC     Treatment trade-off interview       Satisfaction   21   65   55     Both   All   57% wanted an active or collaborative role in treatment in decisions. There was a discrepancy between desired and actual role in 29%   (215)  1998   Cross-section     Interviews       Decision   81   65   33     NSCLC   IIIB and IV   Median threshold 3-mo survival benefit for mild toxicity, 9 mo for moderate. Wide variation, but only 22% would take chemo for 3-mo benefit (all were previously treated)   (216)  1997   Cross-section     Interviews       Decision   56   69   19     Both   All   Wide variation in threshold for taking chemo along with RT for locally advanced disease. Nurse were less likely to take multimodality treatment   (217)  1998   Cross-section     Interviews       Decision   56   69   19     Both   All   This interview method is feasible and reliable   (218)  1997   DA   chemo-RT vs. RT alone         Decision           NSCLC   Locally advanced   Patient preferences are important for deciding about multimodality treatment   (219)  2000   RC   RT         Decision   242   57   8     NSCLC   All   A decision support system with a prognostic index can help decide which patients to treat radically and which to treat palliatively   (220)  2000   Cross-section   chemo for unresectable NSCLC   Questionnaire       Decision   247   65   13     NSCLC   All   The choice whether to take chemo is difficult for patients, compared with students or health care providers, and is independent of how optimistically the information is presented   (221)  2000   PC   POMS         Decision   939   63   38   16   Both   IV   SUPPORT: LC patients were more likely to want comfort care only, without mechanical ventilation, than chronic obstructive pulmonary disease patients. Still, they experienced substantial dyspnea and pain   (222)  2000   PC   Interviews         Decision   747   64   35   15   Both   IV   SUPPORT: patients prefer comfort care as death approaches. Still, they often suffer from pain and confusion   (223)  1997   PC   Usual care   Interviews   Self-administered questionnaire for MDs   Communication   100   65   25       Both   All   Many patients do not understand their situation very well   (224)  1993   Cross-section   Usual care   Interviews       Communication   50   63   36     Both   All   Patients want to be told their diagnoses truthfully and want information about the disease and prognosis   (225)  1998   Cross-section   RT CHART, conventional   Interviews       Communication   24   62   33   7   NSCLC   I-IIIB   Patients wanted more information on side effects   Reference No.   Year   Design   Intervention   Measure 1   Measure 2   Measure 3   Outcome   n   Age, y   F   Nonwhite   Histology   Stage   Result   *ACE = doxorubicin (Adriamycin), cyclophosphamide, and etoposide; ATP = adenosine 5′ -triphosphate; AUC = area under the curve; bronch = bronchoscopy; BSC = best supportive care; bx = biopsy; CAP = cyclophosphamide, doxorubicin, and cisplatin; Carbo = carboplatin; CARES-SF = Cancer Rehabilitation Evaluation System—Short Form; CAV = cyclophosphamide, doxorubicin (Adriamycin), and vincristine; CDI = Clinical Dyspnea Index; CEA = cost-effectiveness analysis; CHART = continuous hyperfractionated accelerated radiation therapy; chemo = chemotherapy; CMA = cost-minimization analysis; CODE = cisplatin, vincristine, doxorubicin, and etoposide; CT = computed tomography; CUA = cost-utility analysis; cyclo = cyclophosphamide; DA = decision analysis; EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; EP = etoposide plus cisplatin; EUS = endoscopic ultrasound; F = proportion of females in the study sample; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module; FDG = fluorodeoxyglucose; FLIC = Functional Living Index—Cancer; FNA = fine-needle aspiration; fx = fractions of radiotherapy; G-CSF = granulocyte colony-stimulating factor; Gem = gemcitabine; H = Hounsfield units; HADS = Hospital Anxiety and Depression Scale; HUI = Health Utility Index; I = ifosphamide; IA = ifosphamide plus doxorubicin (Adriamycin); ICE = ifosphamide, carboplatin, and etoposide; IEP = ifosphamide, epirubicin, and cisplatin; IV = intravenous; LASA = Linear Analogue Self-Assessment; LC = lung cancer; LCSS = Lung Cancer Symptom Scale; LOS = length of stay; M = mitomycin C; MD = physicians; mede = mediastinoscopy; MIP = mitomycin, ifosphamide, and cisplatin; MRC = British Medical Research Council; MVP = mitomycin, vinblastine, and cisplatin; n = sample size; NSCLC = non-small-cell lung cancer; NVB = vinorelbine; P = cisplatin; PAIS = Psychosocial Adjustment to Illness Scale; PC = prospective cohort; PCI = prophylactic cranial irradiation; PET = positron emission tomography; Ph = phase; po = oral; POMS = Profile of Mood States; PR = partial tumor response; PRQ = Personal Resource Questionnaire; PRUI = Pneumoconiosis Research Unit Index; QLCL-E4 = Quality of Life Checklist—Enjoyment, Four Questions; QLI = Quality of Life Index; QoL = quality of life; RC = retrospective cohort; RCT = randomized controlled trial; RR = response rate; RSC = Rotterdam Symptom Checklist; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SCL-90 = Symptom Checklist—90; SCLC = small-cell lung cancer; SIP = Sickness Impact Profile; SSQ = Subjective Significance Questionnaire; STAI = State-Trait Anxiety Inventory; Taxol = paclitaxel; SUPPORT = Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments; UNC = University of North Carolina; VATS = video-assisted thoracoscopy; VBL = vinblastine; VDS = vindesine; VNSSL = video-assisted non-rib spreading lobectomy; VP = vindesine and cisplatin; VP-16 = etoposide; YAG = yttrium laser.   (22)  1999   RCT   NVB vs. BSC   EORTC QLQ-C30   EORTC LC13     Qol   154   > 70   13     NSCLC   IIIB and IV   Stopped early because of poor accrual. NVB increased survival and overall QoL   (106)  1998   RCT   CHART vs. conventional RT   RSC   HADS     QoL   356   65   23     NSCLC   I-IIIB   Transient esophagitis with CHART, but otherwise similar QoL   (81)  1998   PC   RT (CHART, conventional)   RSC   HADS     QoL   2300   65   23     Both   I-IIIB   More consistency when instruments administered by trained staff   (40)  1998   RCT   Taxol-P vs. teniposide-P   EORTC QLQ-C30   EORTC LC13     QoL   317   59   30     NSCLC   IIIA-IV   Taxol better at 6 wk; effect lost at 12 wk   (107)  1998   PC   CAV/EP vs. CODE   EORTC QLQ-C30   SSQ     QoL   111   58       SCLC   Extensive   SSQ used to define small, moderate, or large changes in the EORTC QLQ-C30   (108)  1997   RCT   CAV/EP vs. po VP-16   RSC   MRC daily diary card     QoL   155   67   46     SCLC   All   po VP-16 had inferior survival and QoL   (109)  1996   RCT   EP +/- megace   LASA       QoL   252     40     SCLC   Extensive   Megace resulted in decreased response and survival, similar QoL   (110)  1994   RCT   EP +/- hydrazine   FLIC       QoL   237     32     NSCLC   IIIB and IV   Survival trend worse with hydrazine, similar QoL   (24)  1994   RCT   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Survival similar with hydrazine, but QoL worse (e.g., neutropenia)   (111)  1999   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Pain predicted survival better than did overall QoL   (90)  1997   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Although it did not change the outcome of the trial, QoL assessment added understanding of the patients' perspective on toxicity, etc.   (41)  1999   Ph II   96-h Taxol   FACT-G   FACT-L     QoL   13   56   61     NSCLC   IIIB and IV   Only 3 of 13 patients were able to complete 3 questionnaires because of progressive disease   (42)  1998   Ph II   MVP   EORTC QLQ-C30   EORTC LC13     QoL   50   66   34     SCLC   All   QoL improved from baseline   (78)  1994   PC   Megace   EORTC QLQ-C30   QLCL-E4 (enjoyment)     QoL   20         NSCLC     Fatigue, appetite, among others, correlate better with overall QoL than does weight gain   (82)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30       QoL   100         NSCLC   I-IIIB   Only 34% completed questionnaires. QoL better with lobectomy than with pneumonectomy   (54)  1997   PC   RT for NSCLC   RSC   HADS     QoL   98         NSCLC     Used factor analysis to map RSC and HADS onto EuroQoL and HUI for utility determination   (112)  1996   PC   chemo   Holmes QoL checklist   STA1     QoL   50   58       NSCLC   IIIA-IV   Anxiety levels and personality type correlate with QoL effects   (79)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30   Spitzer Index     QoL   52   52   27     NSCLC     QoL is restored 3-6 mo after surgery   (113)  1998   Ph II   ICE   MRC daily diary card       QoL   30   60   57     SCLC   All   QoL satisfactory, but worse on the first day of each cycle   (19)  1997   PC   chemo   LCSS       QoL   673   61   32     NSCLC   IIIA-IV   Frequent QoL measurements are needed, and AUC may be useful   (43)  1998   RCT   Carbo + VP-16   EORTC QLQ-C30   EORTC LC13     QoL   150   64   41     NSCLC   IIIB and IV   The chemotherapy resulted in improved survival and QoL   (23)  1998   Ph I   Carbo + po VP-16   LCSS       QoL   46   > 70   15     NSCLC   IIIB and IV   QoL improved in 41% and was a better predictor of survival than was response   (83)  1997   RC   RT for NSCLC   LCSS       QoL   63   67   15     NSCLC   All   RT appears to have improved QoL   (26)  1997   Ph II   Taxol by 3-h infusion   FACT-G   FACT-L     QoL   20   63   45     NSCLC   IV   Baseline QoL predicted response, but changes in QoL did not correlate with response   (20)  1997   Ph II   3-h Taxol + Carbo   FACT-G   FACT-L     QoL   11   65   0   27   NSCLC   IIIA-IV   QoL improved in most patients   (114)  1997   Randomized Ph II   Carbo + Taxol 175 vs. 225 mg/m2  EORTC QLQ-C30       QoL   49   61   14     NSCLC   IIIA-IV   No difference in QoL   (115)  1997   Ph II   Taxol by 3-h infusion   RSC   HADS     QoL   21   55   25     NSCLC   IIIA-IV   Treatment well tolerated. High completion rate for QoL forms   (21)  1996   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Patients with poor prognostic features had worse QoL at baseline, but more improvement with chemo   (35)  1992   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Mean compliance 49%. Institution strongly predicted compliance   (27)  1995   PC   Usual care   Likert Symptom Scale       QoL   82   64   39     Both   All   Increased symptom distress with advanced disease, young age, and women. QoL predicted survival   (84)  1995   RCT   CAV vs. Carbo + teniposide   EORTC QLQ-C30       QoL   59   58   8     SCLC   Extensive   CAV yielded better survival, equal QoL   (116)  1995   RCT   Weekly EP/IA vs. 3 weekly EP/CAV   MRC daily diary card       QoL   75   62   36     SCLC   All   No difference in survival. QoL better on 3-weekly treatment (every 3 wk)   (117)  1994   PC   Usual care   Hassles Scale   Demands of Illness Inventory   PRQ, PAIS   QoL   56   60   38   16   Both   IIIA-IV   Black patients and patients with more demands of illness had worse psychosocial adjustment   (118)  1994   Ph II   Fotemustine   Spitzer Index       QoL   77   60   14     NSCLC   All   17% RR. QoL stable   (98)  1994   PC   Usual care   LCSS       QoL   207         NSCLC   All   LCSS was feasible, reliable, and valid   (76)  1993   PC   Usual care   EORTC QLQ-C30       QoL   305   63   24     Both   All   EORTC QLQ-C30 was feasible, reliable, and valid   (96)  1993   PC   Usual care   LCSS       QoL   121   59   33     Both   All   LCSS was feasible, reliable, and valid   (119)  1996   PC   Usual care   Interviews       QoL   200   66   44     Both   All   Family life, health, and social life were most important to patients. Family and social life are missed by most QoL instruments   (15)  1993   PC   Usual care   Symptom Distress Scale   CARES-SF     QoL   69   61   100     Both   All   Pain, fatigue, and insomnia were strongly correlated in women with LC   (120)  1992   Cross-section   Usual care   Spiritual Health Inventory       QoL   23     30   8   Both   All   Patients had moderately high levels of spiritual health, but nurses were poorly able to determine this   (25)  1991   RCT   Planned vs. “as required” chemo   MRC daily diary card       QoL   300   65   25     SCLC   All   Survival similar, but patients with planned treatment had better QoL   (18)  1991   PC   Palliative RT   EORTC QLQ-C30   MRC General Condition Scale   MRC Dyspnea Grade   QoL   40   68   18     NSCLC   IIIA-IV   MDs were poor at predicting QoL but were good at detecting changes   (121)  1991   RCT   Maintenance chemo vs. none after 6 mo   MRC daily diary card       QoL   369         SCLC   Limited   Similar survival, better QoL with maintenance chemo   (28)  1991   PC   Usual care   FLIC       QoL   40   62   13   38   NSCLC   IV   QoL predicts survival   (44)  1990   RCT   PCI   MRC daily diary card   EORTC QLQ-C30   Spitzer Index   QoL   53   63   30     SCLC   All   Diaries are reliable and valid. QoL worsens with successive chemo and PCI   (122)  1990   Ph I/II   Cyclo + trimetrexate   LASA       QoL   55   58   1     NSCLC   All   Testing of 9 domains feasible. Stable QoL despite only 4% PR   (123)  1997   Cross-section   Usual care   SF-36       QoL   590   72   48     Both   All   Also had lung, colon, and prostate cancer patients: LC patients were the most debilitated   (124)  1993   Cross-section   Usual care   Interviews   PAIS     QoL   61   60   33   14   Both   All   No relationship between perceived control and psychosocial adjustment   (29)  1994   PC   Various   FLIC       QoL   438         Both   All   QoL predicts survival   (91)  1996   PC   chemo   EORTC QLQ-C30       QoL   305         Both   All   Mixed response of QoL parameters to chemo   (125)  1996   RCT   2 vs. 13 fx   RSC   HADS   MRC daily diary card   QoL   509   66   21     NSCLC   Unresectable   2 fx palliated symptoms faster, but 13 fx had better survival   (88)  1994   PC   Various   EORTC QLQ-C30   EORTC LC13     QoL   883         Both   All   Neuropathy, dyspnea, and pain sections of the instrument need further refinement   (17)  1997   PC   Usual care   Symptom Distress Scale       QoL   60   58   100   13   Both   All   Factor analysis found several clusters of distress   (126)  1994   PC   Thoracotomy   QLI   SIP   CDI, PRUI   QoL   91   63   31     NSCLC   Resectable   QoL deteriorates during the first 3 mo after surgery but improves afterward   (85)  1998   PC   Diagnosis of LC   HADS   EORTC QLQ-C30     QoL   129   68   40     Both   All   Anxiety decreases after the diagnosis of LC has been made   (127)  1994   RCT   RT to primary tumor   POMS   Clinician-completed rating scale   Trail Making B Test   QoL   119   59   33   7   SCLC   Limited   RT improved survival but decreased QoL and distress   (16)  1993   PC   Usual care   CARES-SF   Symptom Distress Scale     QoL   69   61   100   14   Both   All   QoL was predicted most by symptom distress, physical functioning, and recurrence   (31)  1995   PC   Usual care   HADS   RSC   Spitzer Index   QoL   40   60   20     Both   All   Brief QoL scales correlated well with these formal measures, but not with overall QoL   (128)  1992   PC   chemo   Cancer Inventory of Problem Situations       QoL   36   66   19     SCLC   All   QoL improved with chemo   (33)  1991   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   Improvement on the QoL scales correlated with response to treatment   (89)  1992   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   The EORTC questionnaire performed well, except for emotional and social functioning   (129)  1998   RCT   IEP vs. MVP vs. BSC   FLIC   QLI     QoL   107   57       NSCLC   IV   The chemo resulted in improved survival, without a decrease in QoL   (130)  1993   PC   Usual care   Symptom checklist       QoL           Both   All   Checklists draw attention to problems and can be followed over time   (131)  1992   Cross-section   Usual care   Interviews       QoL   30   61   50     Both   All   Caregivers can serve as proxies for patients, but they tend to underestimate physical function   (132)  1992   Cross-section   Usual care   FLIC   Investigator-designed questionnaire     QoL   64   61   23     Both   All   Good reliability and validity for Japanese translation of the FLIC. Cancer patients scored lower than 50 noncancer patients, especially in mood, anxiety, relationships, and physical function   (133)  1999   PC   Usual care   Investigator-developed diary   LASA     QoL   53   62   17     Both   II-IV   Japanese diary form was reliable and valid   (134)  1995   PC   BSC vs. IEP vs. MVP   FLIC   QLI     QoL   118   56   30     NSCLC   IIIB and IV   Thai modifications (T-FLIC and T-QLI) correlated well with each other and Karnofsky performance status   (30)  1998   Ph II   MIP   LASA       QoL   38   38   21     NSCLC   IIIB and IV   39% RR; 58% improved QoL. QoL predicted survival   (135)  1996   PC   Usual care   Locus of control   Symptom checklist     QoL   31   58   13     Both   All   Patients have a more internal locus of control than non-cancer patients. Locus of control and QoL were not related   (136)  1996   Case-control   Usual care   Nottingham Health Profile   EORTC QLQ-C30   EORTC LC13   QoL   232   66   44     Both   All   Interviewer-administered QoL instruments were acceptable and even enjoyable to most patients   (99)  1999   PC   chemo   LCSS       QoL   673   59   32   17   NSCLC   IIIA-IV   Normative scores for this population are presented   (94)  1995   PC   Usual care   FACT-G   FACT-L     QoL   116   60   53   25   Both   All   Test-retest reliability is demonstrated   (32)  1995   PC   Usual care   Therapy Impact Questionnaire       QoL   128   64   7     Both   All   Patient perception of QoL predicted survival   (137)  1994   Cross-section   Usual care   CARES-SF   LASA     QoL   57   62   44   7   Both   Survivors   LC survivors have poorer QoL than colon or prostate cancer survivors   (77)  1994   PC   chemo   EORTC QLQ-C30       QoL   160   58       Both   All   The instrument is sensitive to the effects of chemo administration and tumor stage   (36)  1994   RCT   chemo   RSC   HADS     QoL   310     37     SCLC   All   Explored ways of dealing with attrition and missing information   (97)  1994   PC   chemo   LCSS   Brief Symptom Inventory   SCL-90, POMS, SIP   QoL   144   59       NSCLC   IIIA-IV   Confirmed construct validity   (138)  1993   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   127         SCLC   All   Fatigue and malaise are important predictors of QoL   (139)  2000   Cross-section   PET vs. mede for staging   Numerical rating scale       QoL   23   57       NSCLC   All   Patients prefer noninvasive staging. Disease extent is the major determinant of utility   (140)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   Clinical benefit     QoL   207   59   18     NSCLC   IIIB and IV   Survival favored docetaxel. Nausea, pain, and dyspnea improved with docetaxel, with a trend toward improved global QoL   (141)  1999   RCT   Gem vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   147   59   23     NSCLC   IIIA-IV   No difference between arms in survival or QoL, although less toxicity in Gem arm   (142)  2000   PC   None   Symptom Distress Scale   Thurstone scale     QoL   26   66   50     Both   All   Fatigue was the most intense symptom, but it ranked second last on the Thurstone scale   (143)  1999   PC   None   Freiburg Questionnaire of Coping With Illness   A uniquely developed Depression Scale   QoL   103   59   17       Both   All   Depressive coping and emotional distress correlate with shorter survival   (37)  1999   Ph II   Gem   EORTC QLQ-C30   EORTC LC13     QoL   30   59   10     NSCLC   IIIB and IV   20% RR. Cough was the only aspect of QoL that changed substantially, improving after 3 cycles   (144)  2000   PC   Palliative RT   EORTC QLQ-C30   EORTC LC13     QoL   69         NSCLC   All   QoL, especially dyspnea and social functioning, improved in those with objective tumor response   (145)  2000   PC   High-dose palliative RT   EORTC QLQ-C30       QoL   42   70       Both   All   Patients had improved QoL after treatment. Regression models were fitted on the basis of both time since treatment and time left to live   (146)  2000   Ph I/II   High-dose EP   EORTC QLQ-C30   EORTC LC13     QoL   42   57   22     NSCLC   IIIA-IV   RR of 33%. QoL stable, with improved emotional status but worsening fatigue   (147)  2000   RCT   Gem vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   300   65   37     NSCLC   IIIA-IV   QoL was the main end point. Pain, cough, and fatigue all improved > 10%. There was no difference in survival. 19% PR   (38)  2000   Ph II   Gem + NVB   EORTC QLQ-C30   EORTC LC13     QoL   126   63   12     NSCLC   IIIB and IV   Dropout was a big problem   (39)  2000   Ph II   NVB   Therapy Impact Questionnaire       QoL   46   75   13     NSCLC   All   After baseline, large amounts of missing data. Patients often required help to complete questionnaires. QoL stable throughout treatment   (148)  2000   Ph II   Taxol-ifosphamide-P   LCSS       QoL   50   58   12     NSCLC   IIIA-IV   64% tumor RR. QoL improved in 74%   (149)  1999   PC   Informed consent   HADS       QoL   119   65   36     NSCLC   All   Informed consent increases anxiety and depression, especially in women and patients with poor performance status   (34)  2000   PC   RT   EORTC QLQ-C30   EORTC LC13     QoL   198     15     NSCLC   I-IIIB   Global QoL predicts survival for lymph node-positive patients   (150)  2000   PC   Usual care   SF-36   Symptom Experience Scale     QoL   129   72   42   5   Both   All   Younger patients, patients with higher previous physical function, and patients with more current symptoms experienced greater loss of function   (151)  1999   PC   RT   Quality adjusted survival time       QoL   979         NSCLC   II-IIIB   Two authors chose weights for different toxic effects and calculated Q time for different therapies based on prior RTOG studies   (152)  2000   RCT   Taxol vs. BSC   RSC       QoL   157   64   25     NSCLC   IIIB and IV   Functional ability improved with Taxol. Otherwise, no difference   (153)  2000   RCT   ATP vs. BSC   RSC       QoL   58   62   35     NSCLC   IIIB and IV   QoL deteriorated in the control group but not in the ATP group   (154)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   RSC     QoL   104   61   31     NSCLC   IIIB and IV   QoL will be reported separately: less worsening in docetaxel arm   (155)  2000   PC   Usual care   HADS   RSC     QoL   1189         Both   Advanced   Depression more common in SCLC patients, among women, and in more debilitated patients   (95)  2000   RCT   Taxol-P vs. EP   FACT-G   FACT-L     QoL   599   62   36   13   NSCLC   IIIB and IV   Trend toward improved QoL on the Taxol arm   (156)  2000   RCT   ACE every 2 wk with G-CSF vs. ACE every 3 wk   RSC       QoL   403   61   42     SCLC   All   Survival was improved with similar QoL in the intensively treated patients   (157)  1999   RCT   Gem-P vs. MIP   EORTC QLQ-C30   EORTC LC13     QoL   307   61   24     NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR with similar QoL, survival, and time to disease progression   (86)  1999   RCT   MIP vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   820   64   25     NSCLC   IIIA-IV   MIP improved survival with improved QoL   (158)  1999   RCT   Gem-P vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   135   59   7   1   NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR and delayed disease progression; QoL was similar   (159)  2000   RCT   Gem-NVB vs. NVB   LCSS       QoL   120   75   6     NSCLC   IIIB and IV   Gem-NVB improved survival and time to symptomatic progression; only 40% had a decrease in QoL compared with 60% receiving NVB alone   (160)  1999   PC   VATS vs. open thoracotomy   Symptom questionnaire (unique)       QoL   44   62   36     NSCLC   Resectable   VATS resulted in decreased pain and increased satisfaction with the wound   (161)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CEA       Cost     51       Both   All   Open bx is most cost-effective   (45)  1993   RC   Restage responding patients with scans or bronch   CEA       Cost   324   62   45     SCLC   Limited   Restaging is not cost-effective   (162)  1996   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (163)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (164)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (165)  1993   RC   VATS vs. open thoracotomy   CMA       Cost   150   63   57     NSCLC   All   Trend toward decreased operating time and LOS for VATS despite higher equipment costs   (166)  1997   DA   FNA for patients with a history of cancer   CEA       Cost           Both   All   FNA with selected use of thoracoscopy is most cost-effective   (167)  1995   RCT   CT vs. mede   CEA       Cost   685   64   29     NSCLC   Resectable   CT is more cost-effective than mede   (46)  1995   DA   Head CT for staging disease in patients with no neurologic symptoms   CEA       Cost           Both   All   CT head is not cost-effective   (168)  1996   DA   Cytologic brushings for bronchoscopically visible tumors   CEA       Cost           NSCLC   All   Either washings or brushings, but not both, are cost-effective   (53)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CUA       Cost           Both   All   For patients averse to waiting, thoracoscopy is most cost-effective; for those averse to morbidity, expectant waiting is best   (169)  1993   RC   Sequence of staging tests   CMA       Cost   451         SCLC   All   The algorithm can save one-third of costs as long as testing is stopped as soon as metastases are detected   (170)  1998   DA   Diagnosis of LC   CEA       Cost           Both   All   Open bx is most cost-effective in operative candidates; sputum is least   (47)  1998   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Routine use of G-CSF is not cost-effective   (171)  1999   DA   Radon screening and mitigation to prevent LC   CEA       Cost           Both   All   Limiting testing to high-risk geographical areas and requiring a confirmatory test before mitigation are most cost-effective   (172)  1999   RC   Usual care   Cost       Cost   253   71       Both   All   Costs were less than those for Canadian studies because of less aggressive intervention   (173)  1994   RC   Usual care   Cost       Cost   300         Both   All   A “top-down” cost allocation approach is feasible   (174)  1993   RCT   G-CSF during chemo   CMA       Cost   68         SCLC   All   G-CSF could save money in patients at high risk of febrile neutropenia   (48)  1996   DA   Follow-up after curative resection   CMA       Cost           NSCLC   All   There was a fivefold difference in the cost of follow-up strategies, with no evidence of difference in benefit   (175)  1991   RC   Usual care   Cost       Cost   15 381   > 65       Both   All   LC cost $12 510 1984 U.S. dollars   (176)  1996   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost           NSCLC   IIIB and IV   NVB-P was effective and cost-effective   (49)  1999   DA   Conformal vs. standard RT   CMA       Cost           Both   All   Conformal RT was twice as expensive as standard   (177)  1990   PC   chemo   Hospital days       Cost   90     25     SCLC   All   Average 18 days in hospital: 69% of hospital days due to tumor complications   (59)  1996   PC   Gem vs. VP-P vs. VP-I   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (60)  1996   PC   Gem vs. VP-P   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (178)  1995   DA   Gem vs. VP-I   CMA       Cost           NSCLC   IIIA-IV   Excluding drug costs. Gem used fewer resources   (179)  1996   RC   P + either VP-16 or VP-16 phosphate   CMA       Cost   254         SCLC   All   VP-16 phosphate, a prodrug of VP-16 with shorter administration time, consumes fewer resources   (180)  1997   DA   Multimodality treatment   CEA       Cost           NSCLC   III   Multimodality therapy is cost-effective   (181)  1997   DA   Taxol vs. BSC   CEA       Cost           NSCLC   IV   Taxol is cost-effective   (182)  1999   DA   Taxol-P vs. BSC   CEA       Cost           NSCLC   IV   Taxol-P is cost-effective   (183)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (184)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (185)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (186)  1996   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (187)  1993   RC   chemo   CMA       Cost           SCLC   All   Large variation in the cost of regimes with similar efficacy   (188)  1996   DA   NVB vs. NVB-P vs. VP-16-P vs. VBL-P vs. BSC   CEA       Cost           NSCLC   IV   VBL-P is most cost-effective, but NVB-P is most effective and is cost-effective when given in an outpatient setting   (189)  1996   DA   Gem vs. BSC   CEA       Cost           NSCLC   IV   Gem is more costly but is still cost-effective   (190)  1998   RC   Usual care   Cost       Cost   336   <65       NSCLC   All   Type of treatment predicted total cost more than did hospital days   (191)  1990   RCT   CAP vs. VP vs. BSC   CEA       Cost   137         NSCLC   IIIB and IV   The chemo was both effective and cost-effective. In fact, CAP actually saved money   (50)  1995   RCT   CAP vs. VP vs. BSC   CUA       Cost   137         NSCLC   IIIB and IV   Did not confirm the cost-savings found by Jaakkimainen et al. (65) but did find chemo to be cost-effective   (51)  1994   RC   G-CSF during chemo   CMA       Cost   137   62   47     SCLC   All   G-CSF was not cost-effective   (192)  1996   DA   Gem-P vs. NVB-P vs. VP-16-P vs. MIP   CEA       Cost           NSCLC   IIIB and IV   Gem-P had the lowest cost per response   (193)  1992   RC   Usual care   Cost       Cost   39   68       SCLC   All   Hospitalization and chemo drug costs were the main drivers of SCLC costs. QoL did not suffer with intensive chemo   (194)  1995   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost   612         NSCLC   IIIA-IV   As long as NVB's toxicity profile is acceptable, it is effective and cost-effective   (195)  1996   RCT   M-NVB-P vs. M-VDS-P   CEA       Cost   209   61   5     NSCLC   IIIA-IV   M-NVB-P costs less per response   (55)  1997   RCT   CHART vs. conventional RT   CEA       Cost   284   65   21     NSCLC   I-IIIB   CHART more costly but likely cost-effective, given the survival benefits   (56)  1998   DA   Gem vs. EP vs. IE   CMA       Cost           NSCLC   IIIB and IV   Gem cost-saving   (196)  1996   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Based on a meta-analysis showing no survival benefit but reduced incidence of neutropenic fever, G-CSF would have to cost $395-$569 per cycle to be cost neutral   (197)  1992   RCT   po vs. IV VP-16 with P   CMA       Cost   83         SCLC   All   The oral regimen was less costly and equally efficacious   (198)  1995   Ph II   Fazarabine   CMA       Cost   23   65   39     NSCLC   IV   Fazarabine had no activity (0% RR) and similar costs to VP-16-P   (199)  1998   RC   Usual care   Cost       Cost   554   <65   43     Both   All   Hospital charges ≈$35 000 in the last year of life   (200)  1998   RC   VATS vs. open thoracotomy   Cost       Cost   80   56   33     NSCLC   I   VATS wedge resection was less costly, but VATS lobectomy was more costly than the open procedure   (201)  2000   Cross-section   PET added to staging work-up   Questionnaire       Cost   87   55   16     Both   All   Willingness to pay for PET ranged from $1500 to $4000, proportional to perceived risk of cancer and income. Insured vs. Medicaid willing to pay more   (202)  2000   RC   Ph II chemo trials   Cost       Cost   43         Both   IV   The cost of doing Ph II studies is more for a drug that works, as it is given longer, and is driven by imaging studies and laboratory tests. The cost was still less than standard therapy   (203)  2000   RCT   Gem-P vs. VP-16-P   Cost       Cost   135   58   7     NSCLC   IV   Survival was equivalent, although RR and time to progression were superior for Gem-P. Increased cost of the drugs was offset by decreased hospitalization   (62)  2000   RCT   YAG vs. YAG + brachytherapy         Cost   29   61   21     NSCLC   All   Brachytherapy saved money by decreasing the need for repeat procedures. No method described   (52)  2000   DA   Adding PET to chest CT         Cost   56         NSCLC   All   PET unlikely to be a cost-effective addition to the diagnostic work-up in Japan (although it seems to easily meet U.S. standards of cost-effectiveness)   (63)  1999   Case series   VNSSL   Cost       Cost   250     52     Both   Resectable   VNSSL appears efficacious, costs ≈50% of open thoracotomy. No method described   (204)  1999   RCT   Taxol-P vs. teniposide-P   Cost       Cost   62         NSCLC   IV   Taxol-P had a higher RR, at a cost of $21 011 per response   (205)  2000   RC   Follow-up after curative resection   Survival   Cost     Cost   245   64   41     NSCLC   I and II   Most recurrences are found by the family doctor and have equivalent survival to that found by the surgeon. Costs would be 75% less if family doctors did all follow-up, and the results the same   (206)  2000   RCT   Pleural tent after lobectomy   Cost       Cost   50   67   20     NSCLC   Resectable   Pleural tenting reduced air leak, hospital days, and costs   (207)  1999   RC   Staging for early-stage disease   Cost       Cost   755   63   39     NSCLC   I   Metastases were found in only 2.1% of T1N0 and 5.4% of T2N0 tumors. Total cost of unnecessary tests was $924 168   (208)  2000   RCT   CT scan before bronch   Cost       Cost   171   67   38     NSCLC   Resectable   CT averted many invasive procedures, resulting in a lower cost per patient   (209)  1999   DA   EUS/FNA vs. mede   Cost       Cost           NSCLC   Resectable   Despite a lower negative predictive value, EUS was less costly   (57)  1999   DA   Radon screening and mitigation   Cost       Cost           Both   All   Radon remediation is cost-effective from all perspectives in preventing LC   (64)  2000   Case series   Accelerated hyperfractionation   Medicare schedule       Cost   29   68   41     NSCLC   IB-IIIB   Costs only presented in “Discussion” section. Tolerated well, and costs not excessive compared with conventional treatment   (210)  2000   DA   chemo   Cost       Cost           NSCLC   IV   NVB-P is the most cost-effective regimen at conventional thresholds of cost-effectiveness. Gem is most cost-effective when QoL is considered   (58)  2000   DA   Imaging and bx strategies to work up adrenal masses   Cost       Cost           NSCLC   Resectable   Unenhanced CT using a 10 H threshold, followed by magnetic resonance imaging if needed, was the most cost-effective strategy   (211)  1999   RC   Transbronchial needle aspiration   Cost       Cost   99         Both   Resectable   No economic methods given; $27 335 in subsequent procedures estimated to be averted   (70)  1998   RC   Bronch   Record audit   Survey     Quality   2238         Both   All   Variation in histologic distributions may be due to pathologic interpretation   (212)  1998   RC   Usual care   Record audit       Quality   1142   34       Both   All   Median time from first contact to management decision was 18 days; however, time to surgery was 63 days and time to RT was 70 days   (66)  1996   RC   Usual care   Record audit       Quality   312   65   33     SCLC   All   Elderly patients were more likely to get suboptimal care   (71)  1996   PC   Usual care         Quality   622   68   33     Both   All   Substantial variation in referral patterns, diagnostic work-up, and management   (67)  1995   RC   Usual care         Quality   5205   > 65   31   19   NSCLC   All   The elderly are less likely to be treated by all modalities at all stages   (213)  1997   RC   Usual care   Record audit       Quality   107         NSCLC   All   Overuse of testing. Otherwise good compliance with guidelines   (72)  2000   RC   chemo   Administrative data       Quality   6308   74   37   16   NSCLC   IV   Substantial unexplained variation in the use of chemo based on race, geography, and socioeconomic status   (214)  2000   Cross-section           Quality   868   69   30     NSCLC   All   Describes the proportion of patients treated in different ways   (68)  2000   PC           Quality   2182   61   42   18   NSCLC   IV   SUPPORT: older patients get less care   (73)  2000   Cross-section     Survey       Quality   9200         NSCLC   All   Medical oncologists more likely than radiation oncologists to recommend combined modality therapy for stage III disease, emphasizing the importance of multidisciplinary decision making   (69)  1999   RC   Surgery   Administrative data       Quality   10 984   > 65   32   8   NSCLC   I and II   Black patients less likely than white patients to undergo surgery, resulting in inferior survival   (74)  2000   Non-RCT   Computerized QoL surveys in clinic   EORTC QLC-C30   Patient Satisfaction Questionnaire     Satisfaction   53   65   10     Both   All   QoL surveys resulted in more symptoms being addressed. Satisfaction was high and similar in both groups   (75)  1999   PC     Treatment trade-off interview       Satisfaction   21   65   55     Both   All   57% wanted an active or collaborative role in treatment in decisions. There was a discrepancy between desired and actual role in 29%   (215)  1998   Cross-section     Interviews       Decision   81   65   33     NSCLC   IIIB and IV   Median threshold 3-mo survival benefit for mild toxicity, 9 mo for moderate. Wide variation, but only 22% would take chemo for 3-mo benefit (all were previously treated)   (216)  1997   Cross-section     Interviews       Decision   56   69   19     Both   All   Wide variation in threshold for taking chemo along with RT for locally advanced disease. Nurse were less likely to take multimodality treatment   (217)  1998   Cross-section     Interviews       Decision   56   69   19     Both   All   This interview method is feasible and reliable   (218)  1997   DA   chemo-RT vs. RT alone         Decision           NSCLC   Locally advanced   Patient preferences are important for deciding about multimodality treatment   (219)  2000   RC   RT         Decision   242   57   8     NSCLC   All   A decision support system with a prognostic index can help decide which patients to treat radically and which to treat palliatively   (220)  2000   Cross-section   chemo for unresectable NSCLC   Questionnaire       Decision   247   65   13     NSCLC   All   The choice whether to take chemo is difficult for patients, compared with students or health care providers, and is independent of how optimistically the information is presented   (221)  2000   PC   POMS         Decision   939   63   38   16   Both   IV   SUPPORT: LC patients were more likely to want comfort care only, without mechanical ventilation, than chronic obstructive pulmonary disease patients. Still, they experienced substantial dyspnea and pain   (222)  2000   PC   Interviews         Decision   747   64   35   15   Both   IV   SUPPORT: patients prefer comfort care as death approaches. Still, they often suffer from pain and confusion   (223)  1997   PC   Usual care   Interviews   Self-administered questionnaire for MDs   Communication   100   65   25       Both   All   Many patients do not understand their situation very well   (224)  1993   Cross-section   Usual care   Interviews       Communication   50   63   36     Both   All   Patients want to be told their diagnoses truthfully and want information about the disease and prognosis   (225)  1998   Cross-section   RT CHART, conventional   Interviews       Communication   24   62   33   7   NSCLC   I-IIIB   Patients wanted more information on side effects   View Large I thank Candace Canto of the National Library of Medicine for assistance with the literature search. References 1 American Cancer Society. Cancer statistics 2000. CA Cancer J Clin  2000; 50: 7 -33. Google Scholar 2 DeVita VT Jr, Hellman S, Rosenberg S. Cancer: principles and practice of oncology . 4th ed. Philadelphia (PA): Lippincott; 1993. Google Scholar 3 Reis LA, Kosary CL, Hankey BF, Miller BA, editors. SEER cancer statistics review, 1973-1996 . Bethesda (MD): National Cancer Institute; 1999. Google Scholar 4 Thatcher N, Hopwood P, Anderson H. Improving quality of life in patients with non-small cell lung cancer: research experience with gemcitabine. Eur J Cancer  1997 ; 33(Suppl 1): S8 -13. Google Scholar 5 Hollen PJ, Gralla RJ. Comparison of instruments for measuring quality of life in patients with lung cancer. Semin Oncol  1996 ; 23: 31 -40. Google Scholar 6 Hopwood P. Quality of life assessment in chemotherapy trials for non-small cell lung cancer: are theory and practice significantly different. Semin Oncol  1996; 23: 60 -4. Google Scholar 7 Manegold C, Schwarz R. Quality of life and supportive care in the treatment of NSCLC. Chest  1996 ; 109: 113S -114S. Google Scholar 8 Miettinen OS. Screening for lung cancer: can it be cost-effective. CMAJ  2000; 16: 1431 -6. Google Scholar 9 Johnson DH. Evolution of cisplatin-based chemotherapy in non-small cell lung cancer: a historical perspective and the Eastern Cooperative Oncology Group Experience. Chest  2000 ; 117(4 Suppl 1): 133S -137S. Google Scholar 10 Hillner BE. Potential evaluation of the incremental cost-effectiveness of paclitaxel in advanced non-small-cell lung cancer (Eastern Cooperative Oncology Group 5592). J Natl Cancer Inst Monogr  1995; 19: 65 -7. Google Scholar 11 Chang AY, Kim K, Boucher H, Bonomi P, Stewart JA, Karp DD, et al. A randomized phase II trial of echinomycin, trimetrexate, and cisplatin plus etoposide in patients with metastatic nonsmall cell lung carcinoma: an Eastern Cooperative Oncology Group Study (E1587). Cancer  1998 ; 82: 292 -300. Google Scholar 12 Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, et al. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol  1996; 14: 2774 -84. Google Scholar 13 Li B, Yu J, Suntharalingam M, Kennedy AS, Amin PP, Chen Z, et al. Comparison of three treatment options for single brain metastasis from lung cancer. Int.J Cancer  2000 ; 90: 37 -45. Google Scholar 14 White SC, Cheeseman S, Thatcher N, Anderson H, Carrington B, Hearn S, et al. Phase II study of oral topotecan in advanced non-small cell lung cancer. Clin Cancer Res  2000 ; 6: 868 -73. Google Scholar 15 Sarna L. Correlates of symptom distress in women with lung cancer. Cancer Pract  1993; 1: 21 -8. Google Scholar 16 Sarna L. Women with lung cancer: impact on quality of life. Qual Life Res  1993; 2: 13 -22. Google Scholar 17 Sarna L, Brecht ML. Dimensions of symptom distress in women with advanced lung cancer: a factor analysis. Heart Lung  1997 ; 26: 23 -30. Google Scholar 18 Regan J, Yarnold J, Jones PW, Cooke NT. Palliation and life quality in lung cancer: how good are clinicians at judging treatment outcome. Br J Cancer  1991; 64: 396 -400. Google Scholar 19 Hollen PJ, Gralla RJ, Cox C, Eberly SW, Kris MG. A dilemma in analysis: issues in the serial measurement of quality of life in patients with advanced lung cancer. Lung Cancer  1997 ; 18: 119 -36. Google Scholar 20 Roychowdhury DF, Desai P, Zhu YW. Paclitaxel (3-hour infusion) followed by carboplatin (24 hours after paclitaxel): a phase II study in advanced non-small cell lung cancer. Semin Oncol  1997 ; 24: S12 -37-S12-40. Google Scholar 21 Bernhard J, Hurny C, Bacchi M, Joss RA, Cavalli F, Senn HJ, et al. Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK). Br J Cancer  1996 ; 74: 1660 -7. Google Scholar 22 The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  1999 ; 91: 66 -72. Google Scholar 23 Frasci G, Comella P, Panza N, De Cataldis G, Del Gaizo F, Pozzo C, et al. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer  1998; 34: 1710 -4. Google Scholar 24 Kosty MP, Fleishman SB, Herndon JE, Coughlin K, Kornblith AB, Scalzo A, et al. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol  1994; 12: 1113 -20. Google Scholar 25 Earl HM, Rudd RM, Spiro SG, Ash CM, James LE, Law CS, et al. A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer  1991 ; 64: 566 -72. Google Scholar 26 Tester WJ, Jin PY, Reardon DH, Cohn JB, Cohen MH. Phase II study of patients with metastatic nonsmall cell carcinoma of the lung treated with paclitaxel by 3-hour infusion. Cancer  1997 ; 79: 724 -9. Google Scholar 27 Degner LF, Sloan JA. Symptom distress in newly diagnosed ambulatory cancer patients and as a predictor of survival in lung cancer. J Pain Sympt Manage  1995; 10: 423 -31. Google Scholar 28 Ganz PA, Lee JJ, Siau J. Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer  1991 ; 67: 3131 -5. Google Scholar 29 Ruckdeschel JC, Piantadosi S. Quality of life in lung cancer surgical adjuvant trials. Chest  1994 ; 106: 324S -328S. Google Scholar 30 Han JY, Kim HK, Choi BG, Moon H, Hong YS, Lee KS. Quality of life (QOL) assessment of MIP (mitomycin, ifosphamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC). Jpn J Clin Oncol  1998 ; 28: 749 -53. Google Scholar 31 Abratt R, Viljoen G. Assessment of quality of life by clinicians—experience of a practical method in lung cancer patients. S Afr Med J  1995; 85: 896 -8. Google Scholar 32 Buccheri GF, Ferrigno D, Tamburini M, Brunelli C. The patient's perception of his own quality of life might have an adjunctive prognostic significance in lung cancer. Lung Cancer  1995 ; 12: 45 -58. Google Scholar 33 Bergman B, Sullivan M, Sorenson S. Quality of life during chemotherapy for small cell lung cancer. I. An evaluation with generic health measures. Acta Oncol  1991 ; 30: 947 -57. Google Scholar 34 Langendijk H, Aaronson NK, de Jong JM, ten Velde GP, Muller MJ, Wouters M. The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy. Radiother Oncol  2000; 55: 19 -25. Google Scholar 35 Hurny C, Bernhard J, Joss R, Willems Y, Cavalli F, Kiser J, et al. Feasibility of quality of life assessment in a randomized phase III trial of small cell lung cancer—a lesson from the real world—the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol  1992 ; 3: 825 -31. Google Scholar 36 Hopwood P, Stephens RJ, Machin D. Approaches to the analysis of quality of life data: experiences gained from a medical research council lung cancer working party palliative chemotherapy trial. Qual Life Res  1994; 3: 339 -52. Google Scholar 37 Gridelli C, Perrone F, Gallo C, Rossi A, Barletta E, Barzelloni ML, et al. Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial. Anticancer Res  1999; 19: 4535 -8. Google Scholar 38 Gridelli C, Frontini L, Perrone F, Gallo C, Gulisano M, Cigolari S, et al. Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators. Br J Cancer  2000; 83: 707 -14. Google Scholar 39 Buccheri G, Ferrigno D. Vinorelbine in elderly patients with inoperable nonsmall cell lung carcinoma: a phase II study. Cancer  2000; 88: 2677 -85. Google Scholar 40 Giaccone G, Splinter TA, Debruyne C, Kho GS, Lianes P, van Zandwijk N, et al. Randomized study of paclitaxel-cisplatin versus cisplatinteniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol  1998 ; 16: 2133 -41. Google Scholar 41 Socinski MA, Steagall A, Gillenwater H. Second-line chemotherapy with 96-hour infusional paclitaxel in refractory non-small cell lung cancer: report of a phase II trial. Cancer Invest  1999 ; 17: 181 -8. Google Scholar 42 Hickish TF, Smith IE, Nicolson MC, Ashley S, Priest K, Spencer L, et al. A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer. Br J Cancer  1998 ; 77: 1966 -70. Google Scholar 43 Helsing M, Bergman B, Thaning L, Hero U. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Eur J Cancer  1998 ; 34: 1036 -44. Google Scholar 44 Geddes DM, Dones L, Hill E, Law K, Harper PG, Spiro SG, et al. Quality of life during chemotherapy for small cell lung cancer: assessment and use of a daily diary card in a randomized trial. Eur J Cancer  1990 ; 26: 484 -92. Google Scholar 45 Feld R, Pater J, Goodwin PJ, Grossman R, Coy P, Murray N. The restaging of responding patients with limited small cell lung cancer. Is it really useful. Chest  1993 ; 103: 1010 -6. Google Scholar 46 Colice GL, Birkmeyer JD, Black WC, Littenberg B, Silvestri G. Cost-effectiveness of head CT in patients with lung cancer without clinical evidence of metastases. Chest  1995 ; 108: 1264 -71. Google Scholar 47 Chouaid C, Bassinet L, Fuhrman C, Monnet I, Housset B. Routine use of granulocyte colony-stimulating factor is not cost-effective and does not increase patient comfort in the treatment of small-cell lung cancer: an analysis using a Markov model. J Clin Oncol  1998 ; 16: 2700 -7. Google Scholar 48 Virgo KS, Naunheim KS, McKirgan LW, Kissling ME, Lin JC, Johnson FE. Cost of patient follow-up after potentially curative lung cancer treatment. J Thorac Cardiovasc Surg  1996 ; 112: 356 -63. Google Scholar 49 Hohenberg G, Sedlmayer F. Costs of standard and conformal photon radiotherapy in Austria. Strahlenther Onkol  1999 ; 175 Suppl 2: 99 -101. Google Scholar 50 Kennedy W, Reinharz D, Tessier G, Contandriopoulos AP, Trabut I, Champagne F, et al. Cost utility of chemotherapy and best supportive care in non-small cell lung cancer. Pharmacoeconomics  1995 ; 8: 316 -23. Google Scholar 51 Nichols CR, Fox EP, Roth BJ, Williams SD, Loehrer PJ, Einhorn LH. Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor. J Clin Oncol  1994; 12: 1245 -50. Google Scholar 52 Kosuda S, Ichihara K, Watanabe M, Kobayashi H, Kusano S. Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[(18)F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small cell lung carcinoma) in Japan. Chest  2000; 117: 346 -53. Google Scholar 53 Raab SS, Hornberger J. The effect of a patient's risk-taking attitude on the cost effectiveness of testing strategies in the evaluation of pulmonary lesions. Chest  1997 ; 111: 1583 -90. Google Scholar 54 Chancellor JV, Coyle D, Drummond MF. Constructing health state preference values from descriptive quality of life outcomes: mission impossible. Qual Life Res  1997 ; 6: 159 -68. Google Scholar 55 Coyle D, Drummond MF. Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Clin Oncol  1997; 9: 313 -21. Google Scholar 56 Tennvall GR, Fernberg JO. Economic evaluation of gemcitabine single agent therapy compared with standard treatment in stage IIIB and IV non-small cell lung cancer. Med Oncol  1998 ; 15: 129 -36. Google Scholar 57 Kennedy CA, Gray AM, Denman AR, Phillips PS. A cost-effectiveness analysis of a residential radon remediation programme in the United Kingdom. Br J Cancer  1999; 81: 1243 -7. Google Scholar 58 Remer EM, Obuchowski N, Ellis JD, Rice TW, Adelstein DJ, Baker ME. Adrenal mass evaluation in patients with lung carcinoma: a cost-effectiveness analysis. AJR Am J Roentgenol  2000 ; 174: 1033 -9. Google Scholar 59 Copley-Merriman C, Martin C, Johnson N, Sacristan JA, Drings PA, Bosanquet N. Economic value of gemcitabine in non-small cell lung cancer. Semin Oncol  1996; 23: 90 -8. Google Scholar 60 Copley-Merriman C, Corral J, King K, Whiteside R, Voi M, Dorr FA, et al. Economic value of gemcitabine compared to cisplatin and etoposide in non-small cell lung cancer. Lung Cancer  1996 ; 14: 45 -61. Google Scholar 61 Evans WK, Will BP, Berthelot JM, Wolfson MC. The cost of managing lung cancer in Canada. Oncology  1995 ; 9: 147 -53. Google Scholar 62 Chella A, Ambrogi MC, Ribechini A, Mussi A, Fabrini MG, Silvano G, et al. Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Lung Cancer  2000; 27: 169 -75. Google Scholar 63 Lewis RJ, Caccavale RJ, Bocage JP, Widmann MD. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy: a more patient-friendly oncologic resection. Chest  1999 ; 116: 1119 -24. Google Scholar 64 Herskovic A, Fisher J, Orton B, Lee CK, Chang JH, Sandhu T, et al. Accelerated hyperfractionation in patients with non-small cell bronchogenic cancers as a cost-effective and user- and patient-friendly schedule. Cancer Invest  2000; 18: 537 -43. Google Scholar 65 Jaakkimainen L, Goodwin PJ, Pater J. Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in non-small cell lung cancer. J Clin Oncol  1990 ; 8: 1301 -9. Google Scholar 66 Dajczman E, Fu LY, Small D, Wolkove N, Kreisman H. Treatment of small cell lung carcinoma in the elderly. Cancer  1996 ; 77: 2032 -8. Google Scholar 67 Smith TJ, Penberthy LT, Desch CE, Whittemore M, Newschaffer CJ, Hillner BE, et al. Differences in initial treatment patterns and outcomes of lung cancer in the elderly. Lung Cancer  1995 ; 13: 235 -52. Google Scholar 68 Rose JH, O'Toole EE, Dawson NV, Thomas C, Connors AFJ, Wenger NS, et al. Age differences in care practices and outcomes for hospitalized patients with cancer. J Am Geriatr Soc  2000 ; 48(5 Suppl): S25 -32. Google Scholar 69 Bach PB, Cramer LD, Warren JL, Begg CB. Racial differences in the treatment of early-stage lung cancer. N Engl J Med  1999 ; 341: 1198 -205. Google Scholar 70 McLean AN, Semple PA, Franklin DH, Petrie G, Millar EA, Douglas JG. The Scottish multi-centre prospective study of bronchoscopy for bronchial carcinoma and suggested audit standards. Respir Med  1998 ; 92: 1110 -5. Google Scholar 71 Fergusson RJ, Gregor A, Dodds R, Kerr G. Management of lung cancer in south east Scotland. Thorax  1996 ; 51: 569 -74. Google Scholar 72 Earle CC, Venditti LN, Neumann PJ, Gelber RD, Weinstein MC, Potosky AL, et al. Who gets chemotherapy for metastatic lung cancer. Chest  2000; 117: 1239 -46. Google Scholar 73 Choy H, Shyr Y, Cmelak AJ, Mohr PJ, Johnson DH. Patterns of practice survey for nonsmall cell lung carcinoma in the U.S. Cancer  2000; 88: 1336 -46. Google Scholar 74 Taenzer P, Bultz BD, Carlson LE, Speca M, DeGagne T, Olson K, et al. Impact of computerized quality of life screening on physician behaviour and patient satisfaction in lung cancer outpatients. Psychooncology  2000; 9: 203 -13. Google Scholar 75 Davidson JR, Brundage MD, Feldman-Stewart D. Lung cancer treatment decisions: patients' desires for participation and information. Psychooncology  1999; 8: 511 -20. Google Scholar 76 Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst  1993 ; 85: 365 -76. Google Scholar 77 Osoba D, Zee B, Pater J, Warr D, Kaizer L, Latreille J. Psychometric properties and responsiveness of the EORTC Quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer. Qual Life Res  1994; 3: 353 -64. Google Scholar 78 Osoba D, Murray N, Gelmon K, Karsai H, Knowling M, Shah A, et al. Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy. Oncology (Huntingt)  1994 ; 8: 61 -5. Google Scholar 79 Zieren HU, Muller JM, Hamberger U, Pichlmaier H. Quality of life after surgical therapy of bronchogenic carcinoma. Eur J Cardiothorac Surg  1996; 10: 233 -7. Google Scholar 80 Spilker B. Quality of life and pharmacoeconomics in clinical trials . 2nd ed. Philadelphia (PA): Lippincott-Raven; 1996 . Google Scholar 81 Hopwood P, Harvey A, Davies J, Stephens RJ, Girling DJ, Gibson D, et al. Survey of the administration of quality of life (QL) questionnaires in three multicentre randomised trials in cancer. The Medical Research Council Lung Cancer Working Party the CHART Steering Committee. Eur J Cancer  1998; 34: 49 -57. Google Scholar 82 Hendriks J, Van Schil P, van Meerbeeck J, Gdeedo A, Van Marck E, Vanmaele R, et al. Short-term survival after major pulmonary resections for bronchogenic carcinoma. Acta Chir Belg  1996 ; 96: 273 -9. Google Scholar 83 Lutz ST, Huang DT, Ferguson CL, Kavanagh BD, Tercilla OF, Lu J. A retrospective quality of life analysis using the Lung Cancer Symptom Scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys  1997 ; 37: 117 -22. Google Scholar 84 Joss RA, Alberto P, Hurny C, Bacchi M, Leyvraz S, Thurlimann B, et al. Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer. A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol  1995 ; 6: 41 -8. Google Scholar 85 Montazeri A, Milroy R, Hole D, McEwen J, Gillis CR. Anxiety and depression in patients with lung cancer before and after diagnosis: findings from a population in Glasgow, Scotland. J Epidemiol Community Health  1998; 52: 203 -4. Google Scholar 86 Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, et al. Mitomycin, ifosphamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life [see comments]. J Clin Oncol  1999 ; 17: 3188 -94. Google Scholar 87 EORTC Quality of Life. Quality of life questionnaire. QLQ-C30. Available from: http://www.eortc.be/home/qol [Last accessed: 09/25/2001.]. Google Scholar 88 Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M. The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer  1994 ; 30A: 635 -42. Google Scholar 89 Bergman B, Sullivan M, Sorenson S. Quality of life during chemotherapy for small cell lung cancer. II. A longitudinal study of the EORTC Core Quality of Life Questionnaire and comparison with the Sickness Impact Profile. Acta Oncol  1992 ; 31: 19 -28. Google Scholar 90 Herndon JE, Fleishman S, Kosty MP, Green MR. A longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931 [see comments]. Control Clin Trials  1997 ; 18: 286 -300. Google Scholar 91 Kosmidis P. Quality of life as a new end point. Chest  1996; 109: 110S -112S. Google Scholar 92 Cella DF, Tulsky DS, Gray GSB, Linn E, Bonomi A, Silberman M, et al. The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol  1993 ; 11: 570 -9. Google Scholar 93 FACIT Functional Assessment of Chronic Illness Therapy. Available from: http://www.facit.org [Last accessed: 09/25/2001.]. Google Scholar 94 Cella DF, Bonomi AE, Lloyd SR, Tulsky DS, Kaplan E, Bonomi P. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer  1995 ; 12: 199 -220. Google Scholar 95 Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol  2000 ; 18: 623 -31. Google Scholar 96 Hollen PJ, Gralla RJ, Kris MG, Potanovich LM. Quality of life assessment in individuals with lung cancer: testing the Lung Cancer Symptom Scale (LCSS). Eur J Cancer  1993 ; 29A(Suppl 1): S51 -8. Google Scholar 97 Hollen PJ, Gralla RJ, Kris MG, Cox C. Quality of life during clinical trials: conceptual model for the Lung Cancer Symptom Scale (LCSS). Support Care Cancer  1994; 2: 213 -22. Google Scholar 98 Hollen PJ, Gralla RJ, Kris MG, Cox C, Belani CP, Grunberg SM, et al. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale. Cancer  1994; 73: 2087 -98. Google Scholar 99 Hollen PJ, Gralla RJ, Kris MG, Eberly SW, Cox C. Normative data and trends in quality of life from the Lung Cancer Symptom Scale (LCSS). Support Care Cancer  1999; 7: 140 -8. Google Scholar 100 Hollen PJ, Gralla RJ, Liepa AM, Rusthoven JJ. Validation of a quality of life instrument for patients with pleural mesothelioma: Lung Cancer Symptom Scale [abstract 1579]. Proc Am Soc Clin Oncol  2001 ; 20: Google Scholar 101 Lung Cancer Symptoms Scale (LCSS). Available from: http://www.lcssql.com [Last accessed: 09/25/02.]. Google Scholar 102 MAPI Research Institute. QOLID: Quality of life instrument database. Available from: http://www.qlmed.org/LCSS [Last accessed: 09/25/2001.]. Google Scholar 103 Gelber RD, Goldhirsch A, Cole BF, Wieand HS, Schroeder G, Krook JE. A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer. J Natl Cancer Inst  1996; 88: 1039 -45. Google Scholar 104 Goldhirsch A, Gelber RD, Simes RJ, Glasziou P, Coates AS. Costs and benefits of adjuvant therapy in breast cancer: A quality-adjusted survival analysis. J Clin Oncol  1989 ; 7: 36 -44. Google Scholar 105 Patrick DL, Starks KC, Cain RF, Uhlmann RF, Pearlman RA. Measuring preferences for health states worse than death. Med Decis Making  1994; 14: 9 -18. Google Scholar 106 Bailey AJ, Parmar MK, Stephens RJ. Patient-reported short-term and long-term physical and psychologic symptoms: results of the continuous hyperfractionated accelerated [correction of acclerated] radiotherapy (CHART) randomized trial in non-small-cell lung cancer. CHART Steering Committee. J Clin Oncol  1998; 16: 3082 -93. Google Scholar 107 Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol  1998; 16: 139 -44. Google Scholar 108 Souhami RL, Spiro SG, Rudd RM, Ruiz de Elvira MC, James LE, Gower NH, et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy [see comments]. J Natl Cancer Inst  1997; 89: 577 -80. Google Scholar 109 Rowland KMJ, Loprinzi CL, Shaw EG, Maksymiuk AW, Kuross SA, Jung SH, et al. Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study. J Clin Oncol  1996; 14: 135 -41. Google Scholar 110 Loprinzi CL, Goldberg RM, Su JQ, Mailliard JA, Kuross SA, Maksymiuk AW, et al. Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol  1994 ; 12: 1126 -9. Google Scholar 111 Herndon JE, Fleishman S, Kornblith AB, Kosty M, Green MR, Holland J. Is quality of life predictive of the survival of patients with advanced nonsmall cell lung carcinoma. Cancer  1999 ; 85: 333 -40. Google Scholar 112 Nakada S, Nagao K, Takiguchi Y, Tatsumi K, Kuriyama T. Quality of life and anxiety before and after lung cancer chemotherapy: relationship to patient's personality. Intern Med  1996 ; 35: 611 -6. Google Scholar 113 Shevlin PM, Muers MF, Peake MD, Hosker HS, Stead ML, Poulter KM, et al. Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosphamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer. Lung Cancer  1998 ; 21: 115 -26. Google Scholar 114 Kosmidis P, Mylonakis N, Fountzilas G, Samantas E, Athanassiadis A, Pavlidis N, et al. Paclitaxel (175 mg/m2) plus carboplatin versus paclitaxel (225 mg/m2) plus carboplatin in non-small cell lung cancer: a randomized study. Semin Oncol  1997 ; 24: S12 -30-33. Google Scholar 115 Ranson MR, Jayson G, Perkins S, Anderson H, Thatcher N. Single-agent paclitaxel in advanced non-small cell lung cancer: single-center phase II study using a 3-hour administration schedule. Semin Oncol  1997; 24: S12 -6-9. Google Scholar 116 Gower NH, Rudd RM, Ruiz de Elvira MC, Spiro SG, James LE, Harper PG, et al. Assessment of `quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer. Ann Oncol  1995; 6: 575 -80. Google Scholar 117 Klemm PR. Variables influencing psychosocial adjustment in lung cancer: a preliminary study. Oncol Nurs Forum  1994 ; 21: 1059 -62. Google Scholar 118 Pujol JL, Monnier A, Berille J, Cerrina ML, Douillard JY, Riviere A, et al. Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor-prognosis non-small-cell lung cancer. Br J Cancer  1994; 69: 1136 -40. Google Scholar 119 Montazeri A, Milroy R, Gillis CR, McEwen J. Quality of life: perception of lung cancer patients. Eur J Cancer  1996 ; 32A: 2284 -9. Google Scholar 120 Highfield MF. Spiritual health of oncology patients. Nurse and patient perspectives. Cancer Nurs  1992 ; 15: 1 -8. Google Scholar 121 Fayers PM, Bleehen NM, Girling DJ, Stephens RJ. Assessment of quality of life in small-cell lung cancer using a Daily Diary Card developed by the Medical Research Council Lung Cancer Working Party. Br J Cancer  1991; 64: 299 -306. Google Scholar 122 Maasilta PK, Rautonen JK, Mattson MT, Mattson KV. Quality of life assessment during chemotherapy for non-small cell lung cancer. Eur J Cancer  1990; 26: 706 -8. Google Scholar 123 Kurtz ME, Kurtz JC, Stommel M, Given CW, Given B. Loss of physical functioning among geriatric cancer patients: relationships to cancer site, treatment, comorbidity and age. Eur J Cancer  1997 ; 33: 2352 -8. Google Scholar 124 Berckman KL, Austin JK. Causal attribution, perceived control, and adjustment in patients with lung cancer. Oncol Nurs Forum  1993 ; 20: 23 -30. Google Scholar 125 Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol)  1996 ; 8: 167 -75. Google Scholar 126 Dales RE, Belanger R, Shamji FM, Leech J, Crepeau A, Sachs HJ. Quality-of-life following thoracotomy for lung cancer. J Clin Epidemiol  1994; 47: 1443 -9. Google Scholar 127 Ahles TA, Silberfarb PM, Rundle AC, Holland JC, Kornblith AB, Canellos GP, et al. Quality of life in patients with limited small-cell carcinoma of the lung receiving chemotherapy with or without radiation therapy, for cancer and leukemia group B. Psychother Psychosom  1994 ; 62: 193 -9. Google Scholar 128 Glimelius B, Birgegard G, Hoffman K, Hagnebo C, Hogman G, Kvale G, et al. Improved care of patients with small cell lung cancer. Nutritional and quality of life aspects. Acta Oncol  1992 ; 31: 823 -31. Google Scholar 129 Thongprasert S. Lung cancer and quality of life. Aust N Z J Med  1998; 28: 397 -9. Google Scholar 130 Osoba D. Self-rating symptom checklists: a simple method for recording and evaluating symptom control in oncology. Cancer Treat Rev  1993; 19(Suppl A): 43 -51. Google Scholar 131 Clipp EC, George LK. Patients with cancer and their spouse caregivers. Perceptions of the illness experience. Cancer  1992 ; 69: 1074 -9. Google Scholar 132 Eguchi K, Fukutani M, Kanazawa M, Tajima K, Tanaka Y, Morioka C, et al. Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer. Jpn J Clin Oncol  1992 ; 22: 185 -93. Google Scholar 133 Ishihara Y, Sakai H, Nukariya N, Kobayashi K, Yoneda S, Matsuoka R, et al. A diary form quality of life questionnaire for Japanese patients with lung cancer and summarization techniques for longitudinal assessment. Respirology  1999; 4: 53 -61. Google Scholar 134 Thongprasert S, Sanquanmitr P. Usefulness of the Thai modified functional living index—cancer (T-FLIC) and the Thai modified quality of life index (T-QLI) for advanced non-small cell lung cancer. Gan To Kagaku Ryoho  1995; 22 (Suppl 3): 226 -9. Google Scholar 135 De Valck C, Vinck J. Health locus of control and quality of life in lung cancer patients. Patient Educ Couns  1996 ; 28: 179 -86. Google Scholar 136 Montazeri A, Milroy R, Gillis CR, McEwen J. Interviewing cancer patients in a research setting: the role of effective communication. Support. Care Cancer  1996; 4: 447 -54. Google Scholar 137 Schag CA, Ganz PA, Wing DS, Sim MS, Lee JJ. Quality of life in adult survivors of lung, colon and prostate cancer. Qual Life Res  1994; 3: 127 -41. Google Scholar 138 Hurny C, Bernhard J, Joss R, Schatzmann E, Cavalli F, Brunner K, et al. “Fatigue and malaise” as a quality-of-life indicator in small-cell lung cancer patients. The Swiss Group for Clinical Cancer Research (SAKK). Support Care Cancer  1993 ; 1: 316 -20. Google Scholar 139 Papatheofanis FJ. Utility evaluations for Markov states of lung cancer for PET-based disease management. Q J Nucl Med  2000 : 44: 186 -90. Google Scholar 140 Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, et al. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer  2000 ; 27: 145 -57. Google Scholar 141 ten Bokkel H, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen PL, et al. Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer  1999 ; 26: 85 -94. Google Scholar 142 Tishelman C, Degner LF, Mueller B. Measuring symptom distress in patients with lung cancer. A pilot study of experienced intensity and importance of symptoms Cancer Nurs  2000 ; 23: 82 -90. Google Scholar [published erratum appears in Cancer Nurs  2000 ; 23: 163 ]. Google Scholar 143 Faller H, Bulzebruck H, Drings P, Lang H. Coping, distress, and survival among patients with lung cancer. Arch Gen Psychiatry  1999 ; 56: 756 -62. Google Scholar 144 Langendijk JA, ten Velde GP, Aaronson NK, de Jong JM, Muller MJ, Wouters EF. Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys  2000 ; 47: 149 -55. Google Scholar 145 Schaafsma J, Coy P. Response of global quality of life to high-dose palliative radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys  2000; 47: 691 -701. Google Scholar 146 Quantin X, Riviere A, Daures JP, Oliver P, Comte-Bardonnet M, Khial F, et al. Phase I-II study of high dose epirubicin plus cisplatin in unresectable non-small-cell lung cancer: searching for the maximal tolerated dose. Am J Clin Oncol  2000 ; 23: 192 -6. Google Scholar 147 Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B, Nicholson M, et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer—a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer  2000 ; 83: 447 -53. Google Scholar 148 Kosmas C, Tsavaris NB, Polyzos A, Kalofonos HP, Sepsas E, Malamos NA, et al. A phase II study of paclitaxel-ifosphamide-cisplatin combination in advanced nonsmall cell lung carcinoma. Cancer  2000 ; 89: 774 -82. Google Scholar 149 Hyodo I, Eguchi K, Takigawa N, Segawa Y, Hosokawa Y, Kamejima K, et al. Psychological impact of informed consent in hospitalized cancer patients. A sequential study of anxiety and depression using the hospital anxiety and depression scale. Support Care Cancer  1999 ; 7: 396 -9. Google Scholar 150 Kurtz ME, Kurtz JC, Stommel M, Given CW, Given BA. Symptomatology and loss of physical functioning among geriatric patients with lung cancer. J Pain Symptom Manage  2000 ; 19: 249 -56. Google Scholar 151 Movsas B, Scott C, Sause W, Byhardt R, Komaki R, Cox J, et al. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies. Int J Radiat Oncol Biol Phys  1999 ; 45: 1143 -9. Google Scholar 152 Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, et al. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  2000; 92: 1074 -80. Google Scholar 153 Agteresch HJ, Dagnelie PC, van der Gaast A, Stijnen T, Wilson JH. Randomized clinical trial of adenosine 5′-triphosphate in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  2000 ; 92: 321 -8. Google Scholar 154 Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol  2000 ; 18: 2095 -103. Google Scholar 155 Hopwood P, Stephens RJ. Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data. J Clin Oncol  2000; 18: 893 -903. Google Scholar 156 Thatcher N, Girling DJ, Hopwood P, Sambrook RJ, Qian W, Stephens RJ. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol  2000 ; 8: 395 -404. Google Scholar 157 Crino L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, et al. Gemcitabine and cisplatin versus mitomycin, ifosphamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol  1999 ; 17: 3522 -30. Google Scholar 158 Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol  1999 ; 17: 12 -8. Google Scholar 159 Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol  2000 ; 18: 2529 -36. Google Scholar 160 Sugiura H, Morikawa T, Kaji M, Sasamura Y, Kondo S, Katoh H. Long-term benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer. Surg Laparosc Endosc Percutan Tech  1999; 9: 403 -8. Google Scholar 161 Goldberg-Kahn B, Healy JC, Bishop JW. The cost of diagnosis: a comparison of four different strategies in the workup of solitary radiographic lung lesions. Chest  1997 ; 111: 870 -6. Google Scholar 162 Gambhir SS, Hoh CK, Phelps ME, Madar I, Maddahi J. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med  1996 ; 37: 1428 -36. Google Scholar 163 Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg  1998; 66: 1876 -83. Google Scholar 164 Gambhir SS, Shepherd JE, Shah BD, Hart E, Hoh CK, Valk PE, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol  1998 ; 16: 2113 -25. Google Scholar 165 Hazelrigg SR, Nunchuck SK, Landreneau RJ, Mack MJ, Naunheim KS, Seifert PE, et al. Cost analysis for thoracoscopy: thoracoscopic wedge resection. Ann Thorac Surg  1993 ; 56: 633 -5. Google Scholar 166 Raab SS, Slagel DD, Hughes JH, Thomas PA, Silverman JF. Sensitivity and cost-effectiveness of fine-needle aspiration with immunocytochemistry in the evaluation of patients with a pulmonary malignancy and a history of cancer. Arch Pathol Lab Med  1997 ; 121: 695 -700. Google Scholar 167 Anonymous. Investigation for mediastinal disease in patients with apparently operable lung cancer. Canadian Lung Oncology Group. Ann Thorac Surg  1995; 60: 1382 -9. Google Scholar 168 Govert JA, Kopita JM, Matchar D, Kussin PS, Samuelson WM. Cost-effectiveness of collecting routine cytologic specimens during fiberoptic bronchoscopy for endoscopically visible lung tumor. Chest  1996 ; 109: 451 -6. Google Scholar 169 Richardson GE, Venzon DJ, Edison M, Brown M, Frame JN, Ihde DC, et al. Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs. Arch Intern Med  1993 ; 153: 329 -37. Google Scholar 170 Gould MK, Lillington GA. Strategy and cost in investigating solitary pulmonary nodules. Thorax  1998 ; 53(Suppl 2): S32 -7. Google Scholar 171 Ford ES, Kelly AE, Teutsch SM, Thacker SB, Garbe PL. Radon and lung cancer: a cost-effectiveness analysis. Am J Public Health  1999 ; 89: 351 -7. Google Scholar 172 Wolstenholme JL, Whynes DK. The hospital costs of treating lung cancer in the United Kingdom. Br J Cancer  1999 ; 80: 215 -8. Google Scholar 173 Coy P, Schaafsma J, Schofield JA, Nield JA. Comparative costs of lung cancer management. Clin Invest Med  1994 ; 17: 577 -87. Google Scholar 174 Glaspy JA, Bleecker G, Crawford J, Stoller R, Strauss M. The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy. Eur J Cancer  1993; 29A(Suppl 7): S23 -30. Google Scholar 175 Baker MS, Kessler LG, Urban N, Smucker RC. Estimating the treatment costs of breast and lung cancer. Med Care  1991 ; 29: 40 -9. Google Scholar 176 Hillner BE, Smith TJ. Cost-effectiveness analysis of three regimens using vinorelbine (Navelbine) for non-small cell lung cancer. Semin Oncol  1996; 23: 25 -30. Google Scholar 177 Bergman B, Sorenson S. Hospitalization during chemotherapy for small cell lung cancer. Acta Oncol  1990 ; 29: 977 -82. Google Scholar 178 Koch P, Johnson N, van Schaik J, Andersen S, Blatter J, Bosanquet N, et al. Gemcitabine: clinical and economic impact in inoperable non-small cell lung cancer. Anticancer Drugs  1995 ; 6(Suppl 6): 49 -54. Google Scholar 179 Doyle JJ, Dezii CM, Sadana A. A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer. Semin Oncol  1996 ; 23: 51 -60. Google Scholar 180 Evans WK, Will BP, Berthelot JM, Earle CC. Cost of combined modality interventions for stage III non-small-cell lung cancer. J Clin Oncol  1997; 15: 3038 -48. Google Scholar 181 Earle CC, Evans WK. A comparison of the costs of paclitaxel and best supportive care in stage IV non-small-cell lung cancer. Cancer Prev Control  1997; 1: 282 -8. Google Scholar 182 Earle CC, Evans WK. Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer. Br J Cancer  1999 ; 80: 815 -20. Google Scholar 183 Evans WK, Will BP, Berthelot JM, Wolfson MC. Diagnostic and therapeutic approaches to lung cancer in Canada and their costs. Br J Cancer  1995; 72: 1270 -7. Google Scholar 184 Evans WK, Will BP, Berthelot JM, Wolfson MC. The cost of managing lung cancer in Canada. Oncology (Huntingt)  1995 ; 9: 147 -53. Google Scholar 185 Evans WK, Will BP, Berthelot JM, Wolfson MC. Estimating the cost of lung cancer diagnosis and treatment in Canada: the POHEM model. Can J Oncol  1995; 5: 408 -19. Google Scholar 186 Evans WK, Will BP, Berthelot JM, Wolfson MC. The economics of lung cancer management in Canada. Lung Cancer  1996 ; 14: 19 -29. Google Scholar 187 Evans WK, Burpee C, Skinn B, Stewart DJ, Stapleton J, Armstrong J, et al. An evaluation of the costs of outpatient chemotherapy administration for small cell lung cancer. Can J Oncol  1993 ; 3: 225 -32. Google Scholar 188 Evans WK, Le Chevalier T. The cost-effectiveness of navelbine alone or in combination with cisplatin in comparison to other chemotherapy regimens and best supportive care in stage IV non-small cell lung cancer. Eur J Cancer  1996; 32A: 2249 -55. Google Scholar 189 Evans WK. An estimate of the cost effectiveness of gemcitabine in stage IV non-small cell lung cancer. Semin Oncol  1996 ; 23: 82 -9. Google Scholar 190 Hillner BE, McDonald MK, Desch CE, Smith TJ, Penberthy LT, Maddox P, et al. Costs of care associated with non-small-cell lung cancer in a commercially insured cohort. J Clin Oncol  1998 ; 16: 1420 -4. Google Scholar 191 Jaakkimainen L, Goodwin PJ, Pater J, Warde P, Murray N, Rapp E. Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer. J Clin Oncol  1990 ; 8: 1301 -9. Google Scholar 192 Palmer AJ, Brandt A. The cost-effectiveness of four cisplatin-containing chemotherapy regimens in the treatment of stages III B and IV non-small cell lung cancer: an Italian perspective. Monaldi Arch Chest Dis  1996; 51: 279 -88. Google Scholar 193 Rosenthal MA, Webster PJ, Gebski VJ, Stuart-Harris RC, Langlands AO, Boyages J. The cost of treating small cell lung cancer. Med J Aust  1992; 156: 605 -10. Google Scholar 194 Smith TJ, Hillner BE, Neighbors DM, McSorley PA, Le Chevalier T. Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small-cell lung cancer. J Clin Oncol  1995 ; 13: 2166 -73. Google Scholar 195 Vergnenegre A, Perol M, Pham E. Cost analysis of hospital treatment—two chemotherapic regimens for non-surgical non-small cell lung cancer. GFPC (Groupe Francais Pneumo Cancerologie). Lung Cancer  1996; 14: 31 -44. Google Scholar 196 Messori A, Trippoli S, Tendi E. G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation. J Clin Pharm Ther  1996 ; 21: 57 -63. Google Scholar 197 Pashko S, Johnson DH. Potential cost savings of oral versus intravenous etoposide in the treatment of small cell lung cancer. Pharmacoeconomics  1992; 1: 293 -7. Google Scholar 198 Williamson SK, Crowley JJ, Livingston RB, Panella TJ, Goodwin JW. Phase II trial and cost analysis of fazarabine in advanced non-small cell carcinoma of the lung: a Southwest Oncology Group study. Invest New Drugs  1995; 13: 67 -71. Google Scholar 199 Polednak AP, Shevchenko IP. Hospital charges for terminal care of cancer patients dying before age 65. J Health Care Finance  1998 ; 25: 26 -34. Google Scholar 200 Sugi K, Kaneda Y, Nawata K, Fujita N, Ueda K, Nawata S, et al. Cost analysis for thoracoscopy: thoracoscopic wedge resection and lobectomy. Surg Today  1998; 28: 41 -5. Google Scholar 201 Papatheofanis FJ. The willingness to pay for positron emission tomography (PET): evaluation of suspected lung cancer using contingent valuation. Q J Nucl Med  2000 ; 44: 191 -6. Google Scholar 202 Evans WK, Dahrouge S, Stapleton J, Quinn C, Pollock D, Waterfield B, et al. An estimate of the cost of conducting phase II trials in lung cancer. Lung Cancer  2000 ; 28: 85 -95. Google Scholar 203 Sacristan JA, Kennedy-Martin T, Rosell R, Cardenal F, Anton A, Lomas M, et al. Economic evaluation in a randomized phase III clinical trial comparing gemcitabine/cisplatin and etoposide/cisplatin in non-small cell lung cancer. Lung Cancer  2000 ; 28: 97 -107. Google Scholar 204 Annemans L, Giaccone G, Vergnenegre A. The cost-effectiveness of paclitaxel (Taxol) + cisplatin is similar to that of teniposide + cisplatin in advanced non-small cell lung cancer: a multicountry analysis. Anticancer Drugs  1999; 10: 605 -15. Google Scholar 205 Gilbert S, Reid KR, Lam MY, Petsikas D. Who should follow up lung cancer patients after operation. Ann Thorac Surg  2000 ; 69: 1696 -700. Google Scholar 206 Brunelli A, Al Refai M, Muti M, Sabbatini A, Fianchini A. Pleural tent after upper lobectomy: a prospective randomized study. Ann Thorac Surg  2000; 69: 1722 -4. Google Scholar 207 Tanaka K, Kubota K, Kodama T, Nagai K, Nishiwaki Y. Extrathoracic staging is not necessary for non-small-cell lung cancer with clinical stage T1-2 N0. Ann Thorac Surg . 1999 ; 68: 1039 -42. Google Scholar 208 Laroche C, Fairbairn I, Moss H, Pepke-Zaba J, Sharples L, Flower C, et al. Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer. Thorax  2000; 55: 359 -63. Google Scholar 209 Aabakken L, Silvestri GA, Hawes R, Reed CE, Marsi V, Hoffman B. Cost-efficacy of endoscopic ultrasonography with fine-needle aspiration vs. mediastinotomy in patients with lung cancer and suspected mediastinal adenopathy. Endoscopy  1999 ; 31: 707 -11. Google Scholar 210 Berthelot JM, Will BP, Evans WK, Coyle D, Earle CC, Bordeleau L. Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer. J Natl Cancer Inst  2000 ; 92: 1321 -9. Google Scholar 211 Crocket JA, Wong EY, Lien DC, Nguyen KG, Chaput MR, McNamee C. Cost effectiveness of transbronchial needle aspiration. Can Respir J  1999 ; 6: 332 -5. Google Scholar 212 Kesson E, Bucknall CE, McAlpine LG, Milroy R, Hole D, Vernon DR, et al. Lung cancer—management and outcome in Glasgow, 1991-92. Br J Cancer  1998; 78: 1391 -5. Google Scholar 213 Walsh GL, Winn RJ. Baseline institutional compliance with NCCN guidelines: non-small-cell lung cancer. Oncology (Huntingt)  1997 ; 11: 161 -70. Google Scholar 214 Richardson GE, Thursfield VJ, Giles GG. Reported management of lung cancer in Victoria in 1993: comparison with best practice. Anti-Cancer Council of Victoria Lung Cancer Study Group. Med J Aust  2000 ; 172: 321 -4. Google Scholar 215 Silvestri G, Pritchard R, Welch HG. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. BMJ  1998 ; 317: 771 -5. Google Scholar 216 Brundage MD, Davidson JR, Mackillop WJ. Trading treatment toxicity for survival in locally advanced non-small cell lung cancer. J Clin Oncol  1997; 15: 330 -40. Google Scholar 217 Brundage MD, Davidson JR, Mackillop WJ, Feldman-Stewart D, Groome P. Using a treatment-tradeoff method to elicit preferences for the treatment of locally advanced non-small-cell lung cancer. Med Decis Making  1998; 18: 256 -67. Google Scholar 218 Brundage MD, Groome PA, Feldman-Stewart D, Davidson JR, Mackillop WJ. Decision analysis in locally advanced non-small-cell lung cancer: is it useful? J Clin Oncol  1997 ; 15: 873 -83. Google Scholar 219 Erkurt E, Tunali C, Erkisi M. Primary therapeutic decision-making in inoperable non-small cell lung cancer. Int J Radiat Oncol Biol Phys  2000; 46: 439 -44. Google Scholar 220 Tamburini M, Buccheri G, Brunelli C, Ferrigno D. The difficult choice of chemotherapy in patients with unresectable non-small-cell lung cancer. Support Care Cancer  2000 ; 8: 223 -8. Google Scholar 221 Claessens MT, Lynn J, Zhong Z, Desbiens NA, Phillips RS, Wu AW, et al. Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am Geriatr Soc  2000 ; 48(5 Suppl): S146 -53. Google Scholar 222 McCarthy EP, Phillips RS, Zhong Z, Drews RE, Lynn J. Dying with cancer: patients' function, symptoms, and care preferences as death approaches. J Am Geriatr Soc  2000 ; 48(5 Suppl): S110 -21. Google Scholar 223 Quirt CF, Mackillop WJ, Ginsburg AD, Sheldon L, Brundage M, Dixon P, et al. Do doctors know when their patients don't? A survey of doctor-patient communication in lung cancer. Lung Cancer  1997 ; 18: 1 -20. Google Scholar 224 Sell L, Devlin B, Bourke SJ, Munro NC, Corris PA, Gibson GJ. Communicating the diagnosis of lung cancer. Respir Med  1993 ; 87: 61 -3. Google Scholar 225 Gamble K. Communication and information: the experience of radiotherapy patients. Eur J Cancer Care (Engl)  1998 ; 7: 153 -61. Google Scholar © Oxford University Press http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI Monographs Oxford University Press

Outcomes Research in Lung Cancer

Earle, Craig C.
JNCI Monographs , Volume 2004 (33) – Oct 1, 2004
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References (233)

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Oxford University Press
Copyright
© Oxford University Press
ISSN
1052-6773
eISSN
1745-6614
DOI
10.1093/jncimonographs/lgh001
pmid
15504920
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Abstract

Abstract Background: Lung cancer is the leading cause of cancer death in the United States. Most therapeutic interventions for this disease achieve modest benefits, but at the expense of nontrivial toxicity and cost, making it an important area for outcomes analysis. Objective: The goal of the study was to audit the literature of outcomes pertaining to lung cancer. Data sources: The English language outcomes literature published during the period from 1990 through 2000 was systematically reviewed and analyzed. Study selection: Papers had to contain original research in one of the following areas: quality of life, health economics, communication, decision making, quality of care, or patient satisfaction. Data extraction: The literature was reviewed and analyzed by the author. Data synthesis: The lung cancer outcomes literature is growing rapidly. Of the 199 studies examined, 106 (53%) dealt primarily with quality-of-life measurement, 69 (35%) examined costs, 11 (6%) dealt with communication and decision making, 11 (6%) assessed the quality of care, and two (1%) evaluated patient satisfaction. Most studies focused on the palliative phase of care. Women, the elderly, and minorities were generally well represented in these studies. The European Organization for Research and Treatment of Cancer QLQ-C30 with its LC13 module is emerging as the most commonly employed quality-of-life instrument in lung cancer studies. Economic studies vary widely in their quality. The literature is relatively sparse with respect to quality of care, communication, and decision making, however. Conclusions: A substantial body of outcomes research has been published since 1990. Further work is needed in the area of methods development, in the assessment of the impact of new technologies, and in the monitoring of the quality of lung cancer care in vulnerable populations. Lung cancer is the leading cause of cancer death in the United States (1). Small-cell lung cancer (SCLC) accounts for approximately 20% of cases, and the balance of cases are referred to as non-small-cell lung cancer (NSCLC), composed mostly of squamous, adenocarcinoma, and large-cell histologies. Most patients present with incurable disease at the time of diagnosis and, because of early hematogenous spread, even those presenting with “ early”-stage disease will often eventually develop incurable metastases (2). The 5-year survival rate for all lung cancer patients is only 15% and has not improved greatly during the past 30 years despite much effort in prevention and therapeutics (3). Surgery is the only treatment modality that can consistently cure a small number of patients with early NSCLC, although radiation therapy can be curative in some limited circumstances. Chemotherapy may contribute in an adjuvant or neoadjuvant role, but it is used mostly as a palliative therapy for advanced disease. SCLC, on the other hand, is more chemosensitive and can be cured in a minority of patients with chemotherapy and radiation therapy. Nevertheless, most patients relapse and die within 1 year of diagnosis (2). Treatments for all stages and histologies of lung cancer are difficult and expensive and come with nontrivial toxicity. Physicians have traditionally evaluated interventions by looking at their effects on tumor shrinkage, time to disease progression, and survival. However, the unsatisfactory results of most lung cancer therapies have led to increasing interest in other end points that affect decision making by patients, payers, and regulators. In this study, I focused on the following broad categories: 1) quality of life, 2) health economics, 3) quality of care, and 4) communication and decision making, as they pertain to lung cancer. This study examines the use of these end points in methodological, descriptive, and intervention studies, as well as economic and decision analyses in order to understand the impact of lung cancer on patients, families, providers, and payers. Methods Literature Search A computerized literature search was done centrally at the National Library of Medicine. It was designed to look for Medical Subject Headings (MeSH) relevant to outcomes research in lung cancer, restricted to English-language articles with on-line abstracts using the following strategy: (quality of life [mh] OR survival analysis [majr] OR health status [mh:noexp] OR health status indicators [mh] OR activities of daily living [mh] OR decision support techniques [majr:noexp] OR decision theory [majr] OR decision making [majr:noexp] OR choice behavior [majr] OR medical futility [majr] OR economics [majr:noexp] OR “costs and cost analysis” [majr] OR cost-benefit analysis [majr] OR economic value of life [majr] OR economics, hospital [majr] OR economics, medical [majr] OR economics, nursing [majr] OR economics, pharmaceutical [majr] OR health services research [mh:noexp] OR delivery of health care [majr:noexp] OR attitude to death [majr] OR attitude to health [majr] OR “health services needs and demand” [majr] OR needs assessment [majr] OR professional-patient relations [majr] OR patient satisfaction [majr] OR physician-patient relations [majr] OR quality of health care [majr:noexp] OR medical audit [majr] OR nursing audit [majr] OR “ outcome and process assessment (health care)” [majr] OR peer review, health care [majr] OR professional review organizations [majr] OR program evaluation [majr] OR quality assurance, health care [majr:noexp] OR guidelines [majr] OR total quality management [majr] OR quality indicators, health care [majr]) AND lung neoplasms [majr] AND english [la] AND journal article [pt] AND 1990: 2000[pdat] AND has abstract. Personal reprints and reference lists were also reviewed. Data Abstraction The study was carried out in two steps. First, for a report to the Outcomes Branch of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, the literature was searched in August 1999 for all articles published during the period from January 1990 through August 1999. In January 2001, this literature search was updated to include all studies published through the end of December 2000. All abstracts were examined, and relevant articles were retrieved. Papers were subsequently excluded if they were found to be reviews, editorials, or opinion pieces or if they were judged not to be outcomes research. Studies that claimed to measure quality of life but did so without an instrument (i.e., relying on the general impressions of the physicians) or that only measured performance status were excluded. Predetermined data elements were abstracted and entered immediately into an electronic database. These included the intervention studied, the type of outcome assessed, measurement instruments used, the study design and perspective, years of data collection, sample size, stages and histology of lung cancer in the study population, percentage of female subjects, percentage of nonwhite subjects, average age of the patients, and a short description of the study findings. For the updated review (August 1999 through December 2000), additional data elements were abstracted, such as the phase of care being addressed by the study, whether the sample size was based on an a priori power calculation, and whether confidence limits were presented around measured estimates. Database manipulation and analyses were carried out by using the Statistical Analysis Software, version 8.01 (SAS Institute, Cary, NC, 1999). Results Literature Search The literature search yielded 860 articles, of which 210 were deemed appropriate for retrieval and review on the basis of the abstract. Of these, 11 were excluded: Six were reviews (4-9), one was an opinion piece (10), and four did not have any true outcomes component (11-14). The remaining 199 studies are described in the Appendix. One hundred six studies (53%) dealt primarily with quality-of-life measurement, followed in number by the 69 (35%) papers that examined costs (Table 1). There were 11 (6%) studies dealing with communication and decision making, 11 (6%) assessing the quality of care, and two (1%) evaluating patient satisfaction. There has been a rise in the number of studies published each year over the course of the decade, most noticeable in the quality-of-life literature (Fig. 1). Table 1. Types of outcomes studies (n = 199) Study   No.   %   Quality of life   106   53   Economic   69   35   Communication/decision making   11   6   Quality of care   11   6   Patient satisfaction   2   1   Study   No.   %   Quality of life   106   53   Economic   69   35   Communication/decision making   11   6   Quality of care   11   6   Patient satisfaction   2   1   View Large Fig. 1. View largeDownload slide Numbers of outcomes studies over time. CEA = cost-effectiveness analyses; QoL = quality-of-life analyses. Fig. 1. View largeDownload slide Numbers of outcomes studies over time. CEA = cost-effectiveness analyses; QoL = quality-of-life analyses. Most studies focused on NSCLC (108 studies, 54%), although many examined both histologies (63 studies, 32%). More than half of the studies (51%) examined patients with all stages of disease, and more than 30% were restricted to the study of advanced, incurable cancer. A prospective cohort study design was most common, being used in 61 (31%) of the studies, followed by quality-of-life or economic companions alongside randomized controlled trials (43 studies, 22%). Sixteen studies (8%) were carried out prospectively alongside phase I or II trials. Thirty-one decision analyses (16% of studies), all but one an economic evaluation, were reported. Retrospective cohorts were assembled in 26 (13%) studies, and 16 studies (8%) carried out cross-sectional surveys. Most studies came from the United States (68 studies, 34%), followed by Canada (33 studies, 17%), and the United Kingdom (25 studies, 13%). The distribution was similar for all outcomes. Eight studies (4%) were international. For studies that included patients, the average sample size was 523; however, this varied widely. Studies of quality of care (mean = 3560 patients) and cost (mean = 624 patients) tended to be the largest. Quality-of-life studies averaged 206 patients, and studies of decision making and communication had 254 patients on average; satisfaction was evaluated in an average of 37 patients. The mean age of patients in lung cancer outcomes studies was 63 years, and 30% of patients were women. There were three studies, all from the same author, that examined quality-of-life issues in cohorts made up exclusively of women (15-17). Only 24 articles (12%) commented on the racial makeup of their study population. All but one, a communication study from the United Kingdom, were U.S. quality-of-life papers. Of those studies that did report a racial distribution, an average of 15% of patients were nonwhite (range, 1%-38%). The age, sex, and racial demographics of patients studied did not differ greatly across the different types of outcomes studies. Levels of comorbidity were generally not reported. Eighty-four percent of the studies dealt with treatment, and 13% evaluated staging work-up. The rest were evenly split between studies of diagnosis and prevention. A priori power calculations for the outcomes end point were made in 13% of prospective randomized studies and in 40% of cross-sectional surveys. A power calculation was never reported as being a consideration in other study designs, such as phase II studies or prospective cohort analyses. Quality of Life Quality-of-life studies were most likely to examine patients with “ lung cancer” not restricted to homogeneous stage (46% of the time) and often were not restricted to a common histologic group either (30% of the time). Of note, more than one-quarter of the studies were primarily methodological in nature. As expected, the majority of quality-of-life studies were prospective, and 27% involved quality-of-life assessment alongside a randomized trial. Another 16% were carried out alongside phase I and II trials. Fifty-seven percent of the studies presented quality-of-life estimates with some indication of variability (e.g., confidence intervals and standard deviation), whereas 43% did not. Instruments More than one-half of the studies used more than one instrument. Forty-one percent used two, and 13% used three or more, for an average of 1.7 instruments per study. When two or more instruments were used in the same study, they were usually used as complementary instruments in a clinical trial. Although generally not paired for methodological reasons, the different instruments tended to show convergent results. The European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire (EORTC QLQ-C30), either alone or with its lung cancer subscale, the LC13, clearly dominates the literature, being used in 39 (37%) studies (Table 2), especially in more recent studies. The next most commonly used scales were the Rotterdam Symptom Checklist (RSC) and the Hospital Anxiety and Depression Scale (HADS), which were often used together in British studies in the early 1990s, along with the British Medical Research Council (MRC) daily diary card. U.S. studies tended to use the domestically developed Lung Cancer Symptom Scale (LCSS) or Functional Assessment of Cancer Therapy with its lung cancer subscale (FACT-L). In six studies, the investigators developed unique, unvalidated instruments to measure quality of life. Table 2. Most frequently used instruments for quality-of-life assessment in lung cancer (n = 106 studies) Measure*  No.†   %   *EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module.   † More than one instrument could be used in a study.   EORTC QLQ-C30   39   37   EORTC LC13   19   18   Rotterdam Symptom Checklist   13   12   Hospital Anxiety and Depression Scale   12   11   Lung Cancer Symptom Scale   9   8   Linear Analogue Self-Assessment   8   8   British Medical Research Council daily diary card   7   7   Functional Living Index—Cancer   6   6   FACT-G and FACT-L   5   5   Spitzer Index   4   4   Measure*  No.†   %   *EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module.   † More than one instrument could be used in a study.   EORTC QLQ-C30   39   37   EORTC LC13   19   18   Rotterdam Symptom Checklist   13   12   Hospital Anxiety and Depression Scale   12   11   Lung Cancer Symptom Scale   9   8   Linear Analogue Self-Assessment   8   8   British Medical Research Council daily diary card   7   7   Functional Living Index—Cancer   6   6   FACT-G and FACT-L   5   5   Spitzer Index   4   4   View Large Findings To date, the results of many of the quality-of-life studies seem predictable. In observational studies, patients starting out with poor quality of life were less likely to receive aggressive treatment. However, health care professionals can underestimate quality of life compared with patient self-reports (18). Furthermore, quality of life can change rapidly and, therefore, should be measured frequently (at least every 3-4 weeks) to get an accurate picture of the disease course (19). A common finding in randomized studies was that the toxicity of treatment was counterbalanced by decreased tumor-related symptoms (4,20-22). Quality of life can improve even with stable disease (23). Quality-of-life studies rarely changed the outcome of an analysis, but there were some examples where both treatment arms yielded similar survival results, and the quality-of-life effects determined the preferred strategy (24,25). The ability of quality-of-life measures to predict response and survival has been shown many times (26-34). Missing data as a result of patient deterioration were frequently cited as a technical problem, however, often resulting in compliance of around 50% or less (22,24,33, 35-43). Simple daily diary cards have been reported to have better completion rates (25,44). Costs Cost studies have tended to focus on NSCLC. There was a flurry of publications on NSCLC in the middle of the decade, which seems to have leveled out somewhat recently. The plurality of papers (43%) reported decision analytic disease and economic models, although a total of 22% collected prospective or retrospective data alongside randomized clinical trials. It is interesting that only eight (12%) of the 69 economic studies reported a clearly negative result for the intervention being assessed (45-52). Fifty-five percent of studies looked only at the resources consumed by lung cancer care or at cost-minimization between two management options, without consideration of treatment effects. Thirty-eight percent were cost-effectiveness studies with some measure of the consequences of intervention in the denominator. Methodologies differed widely between studies. Only two (3%) attempted to incorporate patient preferences in a cost-utility analysis (50,53). These did not use validated utility instruments like the EQ-5D (EuroQol) or the Health Utilities Index (HUI). A non-economic methodological study using data from a lung cancer trial tried to map the RSC and HADS to the EQ-5D and HUI, however (54). Most studies (93%) took the payer's perspective. Only four studies (6%) took a societal perspective, including costs such as patient time and transportation expenses in the numerator (55-58). The rest of the studies either looked at patient's out-of-pocket costs, or the perspective could not be inferred. Still, the types of costs included in these analyses were inconsistent, with some studies, for example, reporting results that excluded the costs of the study drug (59-61). Subjectively, the quality of studies including an economic component varied widely, with several simply stating cost estimates without any methods discussed (62-64). Because of the short survival time of most patients, lung cancer was commonly found to be a relatively inexpensive disease to manage on a cost-per-case basis. However, because of its prevalence, it constitutes an important proportion of total health care expenditures (61). Hospitalization consistently emerged as the main driver of cost. Interventions such as palliative chemotherapy can lead to patients spending fewer days in hospital and requiring less palliative radiotherapy, thus offsetting the cost of the intervention (65). Quality of Care and Satisfaction There were 11 studies dealing with quality-of-care issues and two studies concerned with patient satisfaction. The most consistent theme to emerge from these studies was that there is variation in practice patterns based on both valid medical considerations like age (66-68) and nonmedical factors like race (69), geographic location (70,71), socioeconomic status (72), and the type of physician being consulted (73). Patient satisfaction was found to be enhanced by using quality-of-life surveys taken during visits to the clinic (74) and by identifying how involved patients wanted to be in the decision-making processes (75). Communication and Decision Making The 11 articles pertaining to decision making and doctor—patient communication focused on areas where the treatment decision is controversial, such as multimodality treatment for locally advanced NSCLC and palliative chemotherapy for advanced disease. These studies were generally carried out by using structured interviews, and they reinforced the notion that patients want information about their disease and want to participate in decision making, although there is important individual variation in how involved they want to be. Discussion This systematic review has found that there is a substantial body of work in outcomes research pertaining to lung cancer. Some areas, such as quality-of-life assessment and cost analyses, have received much attention and prominence. Quality-of-care studies, including patient satisfaction, decision making, and doctor-patient communication, appear in publications less often. Unlike other diseases where there are technologies suitable for assessment in several distinct phases of care (screening, primary and adjuvant therapy, follow-up, and survivorship), outcomes research in lung cancer, by virtue of the disease's poor prognosis, is largely focused on palliative care. It is comforting to see that the age, sex, and racial makeup of most studies are similar to those reported for lung cancer in the Surveillance, Epidemiology, and End Results (SEER) Program1(3). It is interesting that race is really only an issue in U.S. studies and is not even noted in studies from other countries. Nevertheless, there remain several areas where further research is needed and where certain vulnerable populations require ongoing vigilance to ensure representation. 1 Editor's note: SEER is a set of geographically defined, population-based, central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research. Quality-of-Life Studies Quality-of-life research in particular has undergone substantial methodological development over the past decade. However, the result is a body of work that has largely included a mixture of tumor stage and histologic types assessed with a wide variety of instruments. Useful clinical information appears to be lacking on the experiences of homogeneous groups of patients receiving specific treatments. The situation is starting to improve, however, as researchers recognize the importance of an intervention's effects on quality of life and move its assessment into the earlier phases of testing. Still, quality-of-life end points rarely figured into the power calculation when designing these trials. This may be appropriate, however, given the relatively low completion rates of quality-of-life surveys discussed below. The EORTC QLQ-C30 is emerging as the most commonly used quality-of-life instrument. This is partly driven by the decision of the MRC to switch from the RSC and HADS to the EORTC scale as a required component of all of its sponsored trials. The EORTC QLQ-C30 has undergone relatively extensive field testing for reliability and validity. Because its first disease-specific module was the lung cancer module, the LC13, much of the early psychometric validation was done in lung cancer patients (44,76-79). Other lung cancer-specific instruments are the FACT-L and the LCSS. All three have undergone fairly extensive reliability and validity testing and appear to have acceptable psychometric properties (5,80). They have never been compared head-to-head, however. All instruments are meant to be self-administered, although the LCSS has an optional observer component. In different studies they were administered in a variety of ways (81), including being sent to physicians to fill out (82), administered by computer (74), or being only partially administered (21,83-86) or scored (38,43). Partial administration was sometimes done in order to focus on the global quality-of-life questions (e.g., questions 29 and 30 of the EORTC QLQ-C30). The use of ad hoc instruments to measure quality of life is decreasing and should continue to be discouraged. The measures described above have undergone extensive field testing, and there is little reason to create new instruments, the results of which are difficult to interpret across studies. The EORTC QLQ-C30 consists of 30 questions in yes/no, Likert, and numerical analogue scale (NAS) formats (87). The yes/no questions have been removed in the most recent version, however. The LC13 adds 13 more questions (88-90). It is estimated to take about 11 minutes to complete (91) and, at the time of this writing, has been translated into 35 languages. The questions are mostly about disease-related symptoms and treatment-related toxicity experienced in the week before the survey. The LC13 is thought to be especially good in situations where patients are relatively ill, but it is lengthy and complicated compared with other instruments. It is unique in including a question about the perceived financial impact of the disease. The FACT-G (92) consists of 34 questions, 28 of which are scored, whereas the FACT-L (93) currently adds seven questions. Questions about hair loss and regret for smoking were taken out in 1995. The FACT-G uses Likert and NAS formats to ask questions about quality of life in the week leading up to its administration. The FACT focuses more on psychosocial dimensions than the EORTC instrument. Consequently, it may be best in situations where patients are not as sick. It has been assessed at a grade 6-7 reading level, and it has been translated into at least 30 languages. Taking up to 10 minutes to administer, it is also a fairly burdensome scale to complete. As a result, the Physical and Functional scales have been combined with the lung cancer module to form the shorter 21 item “Trial Outcome Index” (94,95). The LCSS is only a disease-specific instrument, with no general health component (96-100). It focuses exclusively on the symptoms of lung cancer and does not attempt to assess the toxicity of treatment. Its advantage is its simplicity. It is rated at a grade 2 level of comprehension; consists of only nine visual analogue scales (VAS) (and six optional ones for an observer to fill out), asking about quality of life in the previous 24 hours; and takes only 5-8 minutes to complete (101). However, the lack of a general component makes it difficult to compare across disease sites, and some respondents have difficulty using the VAS. It is recommended that it be given initially as a face-to-face interview to demonstrate the VAS. It has been translated into at least 26 languages (102). Additional Observations Missing data continue to be a big problem in quality-of-life research. This is especially true in lung cancer, because patients are often too sick to complete surveys and usually experience a rapid downhill course (19). The effects of aggressive treatment can contribute to this phenomenon as well. Consequently, censoring is informative, resulting in misleading analyses in which the average quality of life can appear to increase over time as only healthier patients remain. Several studies in this review (22,24,33,35-43) found that only about one-half of the patients had more than a baseline evaluation, making repeated measures analyses and even comparisons of the proportion of patients who improved versus worsened impossible. Some analysts have tried to impute missing data (19), but this is difficult when there is only one measurement from a patient and the specific trajectory of quality of life is uncertain. Others have tried to limit the analysis to those with complete data (36); however, this may not be valid because it assumes uninformative censoring. As a result, some have turned to looking at other measures such as performance status (90) to estimate missing quality-of-life data. Methodological studies developing less burdensome instruments or validating the use of proxy respondents in various situations would be welcome in order to ameliorate the problem of missing data as a result of patient deterioration in lung cancer quality-of-life studies. Because of the short survival of lung cancer patients, the handling of death presents another analytic challenge. Quality of life can be assessed at a fixed time point or at the time of median survival, but this will lead to overestimates because the patients who die before that time, and who most likely had a worse quality of life, will not be included. Some have calculated an area under the survival curve, adjusted for quality of life, to come up with an average daily quality-of-life estimate (19). For example, the Q-TWiST approach assigns death a value of 0 (103,104). However, patients have rated some health states pertinent to lung cancer, such as having constant pain, as being worse than death (105). Cost Studies The number of economic studies peaked in the middle of the decade with the introduction of several new and exciting, though expensive, interventions like multimodality therapy for stages IIIA or IIIB disease and palliative compounds like gemcitabine and paclitaxel. Because there were fewer changes in the management of SCLC, it received less attention. Recent clinical data on the possible effectiveness of expensive technologies such as spiral computed tomography and positron emission tomography scanning in the early detection and staging of lung cancer will probably result in another run of publications in the next few years. The finding in most reports that the study intervention is cost-effective is likely the result of a combination of factors, some benign and some more problematic. Most cost-effectiveness studies probably start with a “back of the envelope” calculations that can tell roughly whether the analysis being considered is likely to yield an important result; those interventions that are not cost-effective are not pursued. Furthermore, negative studies are generally less interesting and are less likely to be submitted or accepted for publication (“publication bias”). However, the wide variation in methodologies reported may also have an effect. Reporting, for example, cost-effectiveness without considering the cost of the drug under evaluation (59-61) could present an inaccurate picture. Publication of methodological and reporting standards by the U.S. Panel on Cost-Effectiveness in 1996 and demands for transparency in published economic models should lead to improvement in the general methodological quality and comparability of studies in the future. Another positive effect should be more focus on the societal, patient, and caregiver costs of undergoing treatment, areas that have received little attention to date. Other Issues Quality of care is an area receiving increasing attention in other areas of medicine, yet few studies have analyzed the quality of lung cancer care. In addition to studies attempting to shine a light on inequities and variation in practice, more research is needed in the areas of patient satisfaction, decision making, communication, and the appropriate use of palliative interventions. Related to this, there seems to have been little qualitative research done to date in lung cancer, compared with other diseases such as breast cancer. Qualitative methods may be able to bring more insight into patients' actual experience of this terrible disease and its treatment. Despite good representation in lung cancer outcomes research, at least in U.S. studies, visible minority patients, the elderly, and women remain at risk for being relatively neglected. Lung cancer is a disease of the elderly and is more common in several minority groups, such as African Americans. Furthermore, lung cancer is increasing in women, whereas the incidence in men has leveled off and has begun to decrease. By addressing the effects of socioeconomic status, literacy, and culture among these groups of patients, outcomes researchers have the opportunity to explore issues of equity and justice in these patients' access to care and the quality of care they receive. Outcomes research, encompassing such elements of health services research as cost-effectiveness analyses and quality-of-life studies, studies looking at nontraditional clinical end points like quality of care and satisfaction, as well as disease modeling and decision analytic studies, is currently represented in all of these facets in the lung cancer literature. There needs to be more agreement on consistent methods, preferred instruments, and consideration of these outcomes early on in the study design, however, in order to increase rigor in the field. For example, including utility estimates in cost-effectiveness analyses is particularly important for most lung cancer interventions, because effects on quality of life must be balanced against what are usually modest benefits from treatment. In the end, the greatest gains will likely come from exploring the relationships among traditional biomedical outcomes like response and survival, symptom measures, functional status scales, and nontraditional outcomes like health-related quality-of-life and satisfaction with care in order to determine in which situations there is sufficient value added to justify expending the resources to gather these additional data. Appendix —Evidence* Reference No.   Year   Design   Intervention   Measure 1   Measure 2   Measure 3   Outcome   n   Age, y   F   Nonwhite   Histology   Stage   Result   *ACE = doxorubicin (Adriamycin), cyclophosphamide, and etoposide; ATP = adenosine 5′ -triphosphate; AUC = area under the curve; bronch = bronchoscopy; BSC = best supportive care; bx = biopsy; CAP = cyclophosphamide, doxorubicin, and cisplatin; Carbo = carboplatin; CARES-SF = Cancer Rehabilitation Evaluation System—Short Form; CAV = cyclophosphamide, doxorubicin (Adriamycin), and vincristine; CDI = Clinical Dyspnea Index; CEA = cost-effectiveness analysis; CHART = continuous hyperfractionated accelerated radiation therapy; chemo = chemotherapy; CMA = cost-minimization analysis; CODE = cisplatin, vincristine, doxorubicin, and etoposide; CT = computed tomography; CUA = cost-utility analysis; cyclo = cyclophosphamide; DA = decision analysis; EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; EP = etoposide plus cisplatin; EUS = endoscopic ultrasound; F = proportion of females in the study sample; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module; FDG = fluorodeoxyglucose; FLIC = Functional Living Index—Cancer; FNA = fine-needle aspiration; fx = fractions of radiotherapy; G-CSF = granulocyte colony-stimulating factor; Gem = gemcitabine; H = Hounsfield units; HADS = Hospital Anxiety and Depression Scale; HUI = Health Utility Index; I = ifosphamide; IA = ifosphamide plus doxorubicin (Adriamycin); ICE = ifosphamide, carboplatin, and etoposide; IEP = ifosphamide, epirubicin, and cisplatin; IV = intravenous; LASA = Linear Analogue Self-Assessment; LC = lung cancer; LCSS = Lung Cancer Symptom Scale; LOS = length of stay; M = mitomycin C; MD = physicians; mede = mediastinoscopy; MIP = mitomycin, ifosphamide, and cisplatin; MRC = British Medical Research Council; MVP = mitomycin, vinblastine, and cisplatin; n = sample size; NSCLC = non-small-cell lung cancer; NVB = vinorelbine; P = cisplatin; PAIS = Psychosocial Adjustment to Illness Scale; PC = prospective cohort; PCI = prophylactic cranial irradiation; PET = positron emission tomography; Ph = phase; po = oral; POMS = Profile of Mood States; PR = partial tumor response; PRQ = Personal Resource Questionnaire; PRUI = Pneumoconiosis Research Unit Index; QLCL-E4 = Quality of Life Checklist—Enjoyment, Four Questions; QLI = Quality of Life Index; QoL = quality of life; RC = retrospective cohort; RCT = randomized controlled trial; RR = response rate; RSC = Rotterdam Symptom Checklist; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SCL-90 = Symptom Checklist—90; SCLC = small-cell lung cancer; SIP = Sickness Impact Profile; SSQ = Subjective Significance Questionnaire; STAI = State-Trait Anxiety Inventory; Taxol = paclitaxel; SUPPORT = Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments; UNC = University of North Carolina; VATS = video-assisted thoracoscopy; VBL = vinblastine; VDS = vindesine; VNSSL = video-assisted non-rib spreading lobectomy; VP = vindesine and cisplatin; VP-16 = etoposide; YAG = yttrium laser.   (22)  1999   RCT   NVB vs. BSC   EORTC QLQ-C30   EORTC LC13     Qol   154   > 70   13     NSCLC   IIIB and IV   Stopped early because of poor accrual. NVB increased survival and overall QoL   (106)  1998   RCT   CHART vs. conventional RT   RSC   HADS     QoL   356   65   23     NSCLC   I-IIIB   Transient esophagitis with CHART, but otherwise similar QoL   (81)  1998   PC   RT (CHART, conventional)   RSC   HADS     QoL   2300   65   23     Both   I-IIIB   More consistency when instruments administered by trained staff   (40)  1998   RCT   Taxol-P vs. teniposide-P   EORTC QLQ-C30   EORTC LC13     QoL   317   59   30     NSCLC   IIIA-IV   Taxol better at 6 wk; effect lost at 12 wk   (107)  1998   PC   CAV/EP vs. CODE   EORTC QLQ-C30   SSQ     QoL   111   58       SCLC   Extensive   SSQ used to define small, moderate, or large changes in the EORTC QLQ-C30   (108)  1997   RCT   CAV/EP vs. po VP-16   RSC   MRC daily diary card     QoL   155   67   46     SCLC   All   po VP-16 had inferior survival and QoL   (109)  1996   RCT   EP +/- megace   LASA       QoL   252     40     SCLC   Extensive   Megace resulted in decreased response and survival, similar QoL   (110)  1994   RCT   EP +/- hydrazine   FLIC       QoL   237     32     NSCLC   IIIB and IV   Survival trend worse with hydrazine, similar QoL   (24)  1994   RCT   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Survival similar with hydrazine, but QoL worse (e.g., neutropenia)   (111)  1999   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Pain predicted survival better than did overall QoL   (90)  1997   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Although it did not change the outcome of the trial, QoL assessment added understanding of the patients' perspective on toxicity, etc.   (41)  1999   Ph II   96-h Taxol   FACT-G   FACT-L     QoL   13   56   61     NSCLC   IIIB and IV   Only 3 of 13 patients were able to complete 3 questionnaires because of progressive disease   (42)  1998   Ph II   MVP   EORTC QLQ-C30   EORTC LC13     QoL   50   66   34     SCLC   All   QoL improved from baseline   (78)  1994   PC   Megace   EORTC QLQ-C30   QLCL-E4 (enjoyment)     QoL   20         NSCLC     Fatigue, appetite, among others, correlate better with overall QoL than does weight gain   (82)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30       QoL   100         NSCLC   I-IIIB   Only 34% completed questionnaires. QoL better with lobectomy than with pneumonectomy   (54)  1997   PC   RT for NSCLC   RSC   HADS     QoL   98         NSCLC     Used factor analysis to map RSC and HADS onto EuroQoL and HUI for utility determination   (112)  1996   PC   chemo   Holmes QoL checklist   STA1     QoL   50   58       NSCLC   IIIA-IV   Anxiety levels and personality type correlate with QoL effects   (79)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30   Spitzer Index     QoL   52   52   27     NSCLC     QoL is restored 3-6 mo after surgery   (113)  1998   Ph II   ICE   MRC daily diary card       QoL   30   60   57     SCLC   All   QoL satisfactory, but worse on the first day of each cycle   (19)  1997   PC   chemo   LCSS       QoL   673   61   32     NSCLC   IIIA-IV   Frequent QoL measurements are needed, and AUC may be useful   (43)  1998   RCT   Carbo + VP-16   EORTC QLQ-C30   EORTC LC13     QoL   150   64   41     NSCLC   IIIB and IV   The chemotherapy resulted in improved survival and QoL   (23)  1998   Ph I   Carbo + po VP-16   LCSS       QoL   46   > 70   15     NSCLC   IIIB and IV   QoL improved in 41% and was a better predictor of survival than was response   (83)  1997   RC   RT for NSCLC   LCSS       QoL   63   67   15     NSCLC   All   RT appears to have improved QoL   (26)  1997   Ph II   Taxol by 3-h infusion   FACT-G   FACT-L     QoL   20   63   45     NSCLC   IV   Baseline QoL predicted response, but changes in QoL did not correlate with response   (20)  1997   Ph II   3-h Taxol + Carbo   FACT-G   FACT-L     QoL   11   65   0   27   NSCLC   IIIA-IV   QoL improved in most patients   (114)  1997   Randomized Ph II   Carbo + Taxol 175 vs. 225 mg/m2  EORTC QLQ-C30       QoL   49   61   14     NSCLC   IIIA-IV   No difference in QoL   (115)  1997   Ph II   Taxol by 3-h infusion   RSC   HADS     QoL   21   55   25     NSCLC   IIIA-IV   Treatment well tolerated. High completion rate for QoL forms   (21)  1996   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Patients with poor prognostic features had worse QoL at baseline, but more improvement with chemo   (35)  1992   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Mean compliance 49%. Institution strongly predicted compliance   (27)  1995   PC   Usual care   Likert Symptom Scale       QoL   82   64   39     Both   All   Increased symptom distress with advanced disease, young age, and women. QoL predicted survival   (84)  1995   RCT   CAV vs. Carbo + teniposide   EORTC QLQ-C30       QoL   59   58   8     SCLC   Extensive   CAV yielded better survival, equal QoL   (116)  1995   RCT   Weekly EP/IA vs. 3 weekly EP/CAV   MRC daily diary card       QoL   75   62   36     SCLC   All   No difference in survival. QoL better on 3-weekly treatment (every 3 wk)   (117)  1994   PC   Usual care   Hassles Scale   Demands of Illness Inventory   PRQ, PAIS   QoL   56   60   38   16   Both   IIIA-IV   Black patients and patients with more demands of illness had worse psychosocial adjustment   (118)  1994   Ph II   Fotemustine   Spitzer Index       QoL   77   60   14     NSCLC   All   17% RR. QoL stable   (98)  1994   PC   Usual care   LCSS       QoL   207         NSCLC   All   LCSS was feasible, reliable, and valid   (76)  1993   PC   Usual care   EORTC QLQ-C30       QoL   305   63   24     Both   All   EORTC QLQ-C30 was feasible, reliable, and valid   (96)  1993   PC   Usual care   LCSS       QoL   121   59   33     Both   All   LCSS was feasible, reliable, and valid   (119)  1996   PC   Usual care   Interviews       QoL   200   66   44     Both   All   Family life, health, and social life were most important to patients. Family and social life are missed by most QoL instruments   (15)  1993   PC   Usual care   Symptom Distress Scale   CARES-SF     QoL   69   61   100     Both   All   Pain, fatigue, and insomnia were strongly correlated in women with LC   (120)  1992   Cross-section   Usual care   Spiritual Health Inventory       QoL   23     30   8   Both   All   Patients had moderately high levels of spiritual health, but nurses were poorly able to determine this   (25)  1991   RCT   Planned vs. “as required” chemo   MRC daily diary card       QoL   300   65   25     SCLC   All   Survival similar, but patients with planned treatment had better QoL   (18)  1991   PC   Palliative RT   EORTC QLQ-C30   MRC General Condition Scale   MRC Dyspnea Grade   QoL   40   68   18     NSCLC   IIIA-IV   MDs were poor at predicting QoL but were good at detecting changes   (121)  1991   RCT   Maintenance chemo vs. none after 6 mo   MRC daily diary card       QoL   369         SCLC   Limited   Similar survival, better QoL with maintenance chemo   (28)  1991   PC   Usual care   FLIC       QoL   40   62   13   38   NSCLC   IV   QoL predicts survival   (44)  1990   RCT   PCI   MRC daily diary card   EORTC QLQ-C30   Spitzer Index   QoL   53   63   30     SCLC   All   Diaries are reliable and valid. QoL worsens with successive chemo and PCI   (122)  1990   Ph I/II   Cyclo + trimetrexate   LASA       QoL   55   58   1     NSCLC   All   Testing of 9 domains feasible. Stable QoL despite only 4% PR   (123)  1997   Cross-section   Usual care   SF-36       QoL   590   72   48     Both   All   Also had lung, colon, and prostate cancer patients: LC patients were the most debilitated   (124)  1993   Cross-section   Usual care   Interviews   PAIS     QoL   61   60   33   14   Both   All   No relationship between perceived control and psychosocial adjustment   (29)  1994   PC   Various   FLIC       QoL   438         Both   All   QoL predicts survival   (91)  1996   PC   chemo   EORTC QLQ-C30       QoL   305         Both   All   Mixed response of QoL parameters to chemo   (125)  1996   RCT   2 vs. 13 fx   RSC   HADS   MRC daily diary card   QoL   509   66   21     NSCLC   Unresectable   2 fx palliated symptoms faster, but 13 fx had better survival   (88)  1994   PC   Various   EORTC QLQ-C30   EORTC LC13     QoL   883         Both   All   Neuropathy, dyspnea, and pain sections of the instrument need further refinement   (17)  1997   PC   Usual care   Symptom Distress Scale       QoL   60   58   100   13   Both   All   Factor analysis found several clusters of distress   (126)  1994   PC   Thoracotomy   QLI   SIP   CDI, PRUI   QoL   91   63   31     NSCLC   Resectable   QoL deteriorates during the first 3 mo after surgery but improves afterward   (85)  1998   PC   Diagnosis of LC   HADS   EORTC QLQ-C30     QoL   129   68   40     Both   All   Anxiety decreases after the diagnosis of LC has been made   (127)  1994   RCT   RT to primary tumor   POMS   Clinician-completed rating scale   Trail Making B Test   QoL   119   59   33   7   SCLC   Limited   RT improved survival but decreased QoL and distress   (16)  1993   PC   Usual care   CARES-SF   Symptom Distress Scale     QoL   69   61   100   14   Both   All   QoL was predicted most by symptom distress, physical functioning, and recurrence   (31)  1995   PC   Usual care   HADS   RSC   Spitzer Index   QoL   40   60   20     Both   All   Brief QoL scales correlated well with these formal measures, but not with overall QoL   (128)  1992   PC   chemo   Cancer Inventory of Problem Situations       QoL   36   66   19     SCLC   All   QoL improved with chemo   (33)  1991   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   Improvement on the QoL scales correlated with response to treatment   (89)  1992   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   The EORTC questionnaire performed well, except for emotional and social functioning   (129)  1998   RCT   IEP vs. MVP vs. BSC   FLIC   QLI     QoL   107   57       NSCLC   IV   The chemo resulted in improved survival, without a decrease in QoL   (130)  1993   PC   Usual care   Symptom checklist       QoL           Both   All   Checklists draw attention to problems and can be followed over time   (131)  1992   Cross-section   Usual care   Interviews       QoL   30   61   50     Both   All   Caregivers can serve as proxies for patients, but they tend to underestimate physical function   (132)  1992   Cross-section   Usual care   FLIC   Investigator-designed questionnaire     QoL   64   61   23     Both   All   Good reliability and validity for Japanese translation of the FLIC. Cancer patients scored lower than 50 noncancer patients, especially in mood, anxiety, relationships, and physical function   (133)  1999   PC   Usual care   Investigator-developed diary   LASA     QoL   53   62   17     Both   II-IV   Japanese diary form was reliable and valid   (134)  1995   PC   BSC vs. IEP vs. MVP   FLIC   QLI     QoL   118   56   30     NSCLC   IIIB and IV   Thai modifications (T-FLIC and T-QLI) correlated well with each other and Karnofsky performance status   (30)  1998   Ph II   MIP   LASA       QoL   38   38   21     NSCLC   IIIB and IV   39% RR; 58% improved QoL. QoL predicted survival   (135)  1996   PC   Usual care   Locus of control   Symptom checklist     QoL   31   58   13     Both   All   Patients have a more internal locus of control than non-cancer patients. Locus of control and QoL were not related   (136)  1996   Case-control   Usual care   Nottingham Health Profile   EORTC QLQ-C30   EORTC LC13   QoL   232   66   44     Both   All   Interviewer-administered QoL instruments were acceptable and even enjoyable to most patients   (99)  1999   PC   chemo   LCSS       QoL   673   59   32   17   NSCLC   IIIA-IV   Normative scores for this population are presented   (94)  1995   PC   Usual care   FACT-G   FACT-L     QoL   116   60   53   25   Both   All   Test-retest reliability is demonstrated   (32)  1995   PC   Usual care   Therapy Impact Questionnaire       QoL   128   64   7     Both   All   Patient perception of QoL predicted survival   (137)  1994   Cross-section   Usual care   CARES-SF   LASA     QoL   57   62   44   7   Both   Survivors   LC survivors have poorer QoL than colon or prostate cancer survivors   (77)  1994   PC   chemo   EORTC QLQ-C30       QoL   160   58       Both   All   The instrument is sensitive to the effects of chemo administration and tumor stage   (36)  1994   RCT   chemo   RSC   HADS     QoL   310     37     SCLC   All   Explored ways of dealing with attrition and missing information   (97)  1994   PC   chemo   LCSS   Brief Symptom Inventory   SCL-90, POMS, SIP   QoL   144   59       NSCLC   IIIA-IV   Confirmed construct validity   (138)  1993   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   127         SCLC   All   Fatigue and malaise are important predictors of QoL   (139)  2000   Cross-section   PET vs. mede for staging   Numerical rating scale       QoL   23   57       NSCLC   All   Patients prefer noninvasive staging. Disease extent is the major determinant of utility   (140)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   Clinical benefit     QoL   207   59   18     NSCLC   IIIB and IV   Survival favored docetaxel. Nausea, pain, and dyspnea improved with docetaxel, with a trend toward improved global QoL   (141)  1999   RCT   Gem vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   147   59   23     NSCLC   IIIA-IV   No difference between arms in survival or QoL, although less toxicity in Gem arm   (142)  2000   PC   None   Symptom Distress Scale   Thurstone scale     QoL   26   66   50     Both   All   Fatigue was the most intense symptom, but it ranked second last on the Thurstone scale   (143)  1999   PC   None   Freiburg Questionnaire of Coping With Illness   A uniquely developed Depression Scale   QoL   103   59   17       Both   All   Depressive coping and emotional distress correlate with shorter survival   (37)  1999   Ph II   Gem   EORTC QLQ-C30   EORTC LC13     QoL   30   59   10     NSCLC   IIIB and IV   20% RR. Cough was the only aspect of QoL that changed substantially, improving after 3 cycles   (144)  2000   PC   Palliative RT   EORTC QLQ-C30   EORTC LC13     QoL   69         NSCLC   All   QoL, especially dyspnea and social functioning, improved in those with objective tumor response   (145)  2000   PC   High-dose palliative RT   EORTC QLQ-C30       QoL   42   70       Both   All   Patients had improved QoL after treatment. Regression models were fitted on the basis of both time since treatment and time left to live   (146)  2000   Ph I/II   High-dose EP   EORTC QLQ-C30   EORTC LC13     QoL   42   57   22     NSCLC   IIIA-IV   RR of 33%. QoL stable, with improved emotional status but worsening fatigue   (147)  2000   RCT   Gem vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   300   65   37     NSCLC   IIIA-IV   QoL was the main end point. Pain, cough, and fatigue all improved > 10%. There was no difference in survival. 19% PR   (38)  2000   Ph II   Gem + NVB   EORTC QLQ-C30   EORTC LC13     QoL   126   63   12     NSCLC   IIIB and IV   Dropout was a big problem   (39)  2000   Ph II   NVB   Therapy Impact Questionnaire       QoL   46   75   13     NSCLC   All   After baseline, large amounts of missing data. Patients often required help to complete questionnaires. QoL stable throughout treatment   (148)  2000   Ph II   Taxol-ifosphamide-P   LCSS       QoL   50   58   12     NSCLC   IIIA-IV   64% tumor RR. QoL improved in 74%   (149)  1999   PC   Informed consent   HADS       QoL   119   65   36     NSCLC   All   Informed consent increases anxiety and depression, especially in women and patients with poor performance status   (34)  2000   PC   RT   EORTC QLQ-C30   EORTC LC13     QoL   198     15     NSCLC   I-IIIB   Global QoL predicts survival for lymph node-positive patients   (150)  2000   PC   Usual care   SF-36   Symptom Experience Scale     QoL   129   72   42   5   Both   All   Younger patients, patients with higher previous physical function, and patients with more current symptoms experienced greater loss of function   (151)  1999   PC   RT   Quality adjusted survival time       QoL   979         NSCLC   II-IIIB   Two authors chose weights for different toxic effects and calculated Q time for different therapies based on prior RTOG studies   (152)  2000   RCT   Taxol vs. BSC   RSC       QoL   157   64   25     NSCLC   IIIB and IV   Functional ability improved with Taxol. Otherwise, no difference   (153)  2000   RCT   ATP vs. BSC   RSC       QoL   58   62   35     NSCLC   IIIB and IV   QoL deteriorated in the control group but not in the ATP group   (154)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   RSC     QoL   104   61   31     NSCLC   IIIB and IV   QoL will be reported separately: less worsening in docetaxel arm   (155)  2000   PC   Usual care   HADS   RSC     QoL   1189         Both   Advanced   Depression more common in SCLC patients, among women, and in more debilitated patients   (95)  2000   RCT   Taxol-P vs. EP   FACT-G   FACT-L     QoL   599   62   36   13   NSCLC   IIIB and IV   Trend toward improved QoL on the Taxol arm   (156)  2000   RCT   ACE every 2 wk with G-CSF vs. ACE every 3 wk   RSC       QoL   403   61   42     SCLC   All   Survival was improved with similar QoL in the intensively treated patients   (157)  1999   RCT   Gem-P vs. MIP   EORTC QLQ-C30   EORTC LC13     QoL   307   61   24     NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR with similar QoL, survival, and time to disease progression   (86)  1999   RCT   MIP vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   820   64   25     NSCLC   IIIA-IV   MIP improved survival with improved QoL   (158)  1999   RCT   Gem-P vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   135   59   7   1   NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR and delayed disease progression; QoL was similar   (159)  2000   RCT   Gem-NVB vs. NVB   LCSS       QoL   120   75   6     NSCLC   IIIB and IV   Gem-NVB improved survival and time to symptomatic progression; only 40% had a decrease in QoL compared with 60% receiving NVB alone   (160)  1999   PC   VATS vs. open thoracotomy   Symptom questionnaire (unique)       QoL   44   62   36     NSCLC   Resectable   VATS resulted in decreased pain and increased satisfaction with the wound   (161)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CEA       Cost     51       Both   All   Open bx is most cost-effective   (45)  1993   RC   Restage responding patients with scans or bronch   CEA       Cost   324   62   45     SCLC   Limited   Restaging is not cost-effective   (162)  1996   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (163)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (164)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (165)  1993   RC   VATS vs. open thoracotomy   CMA       Cost   150   63   57     NSCLC   All   Trend toward decreased operating time and LOS for VATS despite higher equipment costs   (166)  1997   DA   FNA for patients with a history of cancer   CEA       Cost           Both   All   FNA with selected use of thoracoscopy is most cost-effective   (167)  1995   RCT   CT vs. mede   CEA       Cost   685   64   29     NSCLC   Resectable   CT is more cost-effective than mede   (46)  1995   DA   Head CT for staging disease in patients with no neurologic symptoms   CEA       Cost           Both   All   CT head is not cost-effective   (168)  1996   DA   Cytologic brushings for bronchoscopically visible tumors   CEA       Cost           NSCLC   All   Either washings or brushings, but not both, are cost-effective   (53)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CUA       Cost           Both   All   For patients averse to waiting, thoracoscopy is most cost-effective; for those averse to morbidity, expectant waiting is best   (169)  1993   RC   Sequence of staging tests   CMA       Cost   451         SCLC   All   The algorithm can save one-third of costs as long as testing is stopped as soon as metastases are detected   (170)  1998   DA   Diagnosis of LC   CEA       Cost           Both   All   Open bx is most cost-effective in operative candidates; sputum is least   (47)  1998   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Routine use of G-CSF is not cost-effective   (171)  1999   DA   Radon screening and mitigation to prevent LC   CEA       Cost           Both   All   Limiting testing to high-risk geographical areas and requiring a confirmatory test before mitigation are most cost-effective   (172)  1999   RC   Usual care   Cost       Cost   253   71       Both   All   Costs were less than those for Canadian studies because of less aggressive intervention   (173)  1994   RC   Usual care   Cost       Cost   300         Both   All   A “top-down” cost allocation approach is feasible   (174)  1993   RCT   G-CSF during chemo   CMA       Cost   68         SCLC   All   G-CSF could save money in patients at high risk of febrile neutropenia   (48)  1996   DA   Follow-up after curative resection   CMA       Cost           NSCLC   All   There was a fivefold difference in the cost of follow-up strategies, with no evidence of difference in benefit   (175)  1991   RC   Usual care   Cost       Cost   15 381   > 65       Both   All   LC cost $12 510 1984 U.S. dollars   (176)  1996   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost           NSCLC   IIIB and IV   NVB-P was effective and cost-effective   (49)  1999   DA   Conformal vs. standard RT   CMA       Cost           Both   All   Conformal RT was twice as expensive as standard   (177)  1990   PC   chemo   Hospital days       Cost   90     25     SCLC   All   Average 18 days in hospital: 69% of hospital days due to tumor complications   (59)  1996   PC   Gem vs. VP-P vs. VP-I   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (60)  1996   PC   Gem vs. VP-P   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (178)  1995   DA   Gem vs. VP-I   CMA       Cost           NSCLC   IIIA-IV   Excluding drug costs. Gem used fewer resources   (179)  1996   RC   P + either VP-16 or VP-16 phosphate   CMA       Cost   254         SCLC   All   VP-16 phosphate, a prodrug of VP-16 with shorter administration time, consumes fewer resources   (180)  1997   DA   Multimodality treatment   CEA       Cost           NSCLC   III   Multimodality therapy is cost-effective   (181)  1997   DA   Taxol vs. BSC   CEA       Cost           NSCLC   IV   Taxol is cost-effective   (182)  1999   DA   Taxol-P vs. BSC   CEA       Cost           NSCLC   IV   Taxol-P is cost-effective   (183)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (184)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (185)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (186)  1996   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (187)  1993   RC   chemo   CMA       Cost           SCLC   All   Large variation in the cost of regimes with similar efficacy   (188)  1996   DA   NVB vs. NVB-P vs. VP-16-P vs. VBL-P vs. BSC   CEA       Cost           NSCLC   IV   VBL-P is most cost-effective, but NVB-P is most effective and is cost-effective when given in an outpatient setting   (189)  1996   DA   Gem vs. BSC   CEA       Cost           NSCLC   IV   Gem is more costly but is still cost-effective   (190)  1998   RC   Usual care   Cost       Cost   336   <65       NSCLC   All   Type of treatment predicted total cost more than did hospital days   (191)  1990   RCT   CAP vs. VP vs. BSC   CEA       Cost   137         NSCLC   IIIB and IV   The chemo was both effective and cost-effective. In fact, CAP actually saved money   (50)  1995   RCT   CAP vs. VP vs. BSC   CUA       Cost   137         NSCLC   IIIB and IV   Did not confirm the cost-savings found by Jaakkimainen et al. (65) but did find chemo to be cost-effective   (51)  1994   RC   G-CSF during chemo   CMA       Cost   137   62   47     SCLC   All   G-CSF was not cost-effective   (192)  1996   DA   Gem-P vs. NVB-P vs. VP-16-P vs. MIP   CEA       Cost           NSCLC   IIIB and IV   Gem-P had the lowest cost per response   (193)  1992   RC   Usual care   Cost       Cost   39   68       SCLC   All   Hospitalization and chemo drug costs were the main drivers of SCLC costs. QoL did not suffer with intensive chemo   (194)  1995   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost   612         NSCLC   IIIA-IV   As long as NVB's toxicity profile is acceptable, it is effective and cost-effective   (195)  1996   RCT   M-NVB-P vs. M-VDS-P   CEA       Cost   209   61   5     NSCLC   IIIA-IV   M-NVB-P costs less per response   (55)  1997   RCT   CHART vs. conventional RT   CEA       Cost   284   65   21     NSCLC   I-IIIB   CHART more costly but likely cost-effective, given the survival benefits   (56)  1998   DA   Gem vs. EP vs. IE   CMA       Cost           NSCLC   IIIB and IV   Gem cost-saving   (196)  1996   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Based on a meta-analysis showing no survival benefit but reduced incidence of neutropenic fever, G-CSF would have to cost $395-$569 per cycle to be cost neutral   (197)  1992   RCT   po vs. IV VP-16 with P   CMA       Cost   83         SCLC   All   The oral regimen was less costly and equally efficacious   (198)  1995   Ph II   Fazarabine   CMA       Cost   23   65   39     NSCLC   IV   Fazarabine had no activity (0% RR) and similar costs to VP-16-P   (199)  1998   RC   Usual care   Cost       Cost   554   <65   43     Both   All   Hospital charges ≈$35 000 in the last year of life   (200)  1998   RC   VATS vs. open thoracotomy   Cost       Cost   80   56   33     NSCLC   I   VATS wedge resection was less costly, but VATS lobectomy was more costly than the open procedure   (201)  2000   Cross-section   PET added to staging work-up   Questionnaire       Cost   87   55   16     Both   All   Willingness to pay for PET ranged from $1500 to $4000, proportional to perceived risk of cancer and income. Insured vs. Medicaid willing to pay more   (202)  2000   RC   Ph II chemo trials   Cost       Cost   43         Both   IV   The cost of doing Ph II studies is more for a drug that works, as it is given longer, and is driven by imaging studies and laboratory tests. The cost was still less than standard therapy   (203)  2000   RCT   Gem-P vs. VP-16-P   Cost       Cost   135   58   7     NSCLC   IV   Survival was equivalent, although RR and time to progression were superior for Gem-P. Increased cost of the drugs was offset by decreased hospitalization   (62)  2000   RCT   YAG vs. YAG + brachytherapy         Cost   29   61   21     NSCLC   All   Brachytherapy saved money by decreasing the need for repeat procedures. No method described   (52)  2000   DA   Adding PET to chest CT         Cost   56         NSCLC   All   PET unlikely to be a cost-effective addition to the diagnostic work-up in Japan (although it seems to easily meet U.S. standards of cost-effectiveness)   (63)  1999   Case series   VNSSL   Cost       Cost   250     52     Both   Resectable   VNSSL appears efficacious, costs ≈50% of open thoracotomy. No method described   (204)  1999   RCT   Taxol-P vs. teniposide-P   Cost       Cost   62         NSCLC   IV   Taxol-P had a higher RR, at a cost of $21 011 per response   (205)  2000   RC   Follow-up after curative resection   Survival   Cost     Cost   245   64   41     NSCLC   I and II   Most recurrences are found by the family doctor and have equivalent survival to that found by the surgeon. Costs would be 75% less if family doctors did all follow-up, and the results the same   (206)  2000   RCT   Pleural tent after lobectomy   Cost       Cost   50   67   20     NSCLC   Resectable   Pleural tenting reduced air leak, hospital days, and costs   (207)  1999   RC   Staging for early-stage disease   Cost       Cost   755   63   39     NSCLC   I   Metastases were found in only 2.1% of T1N0 and 5.4% of T2N0 tumors. Total cost of unnecessary tests was $924 168   (208)  2000   RCT   CT scan before bronch   Cost       Cost   171   67   38     NSCLC   Resectable   CT averted many invasive procedures, resulting in a lower cost per patient   (209)  1999   DA   EUS/FNA vs. mede   Cost       Cost           NSCLC   Resectable   Despite a lower negative predictive value, EUS was less costly   (57)  1999   DA   Radon screening and mitigation   Cost       Cost           Both   All   Radon remediation is cost-effective from all perspectives in preventing LC   (64)  2000   Case series   Accelerated hyperfractionation   Medicare schedule       Cost   29   68   41     NSCLC   IB-IIIB   Costs only presented in “Discussion” section. Tolerated well, and costs not excessive compared with conventional treatment   (210)  2000   DA   chemo   Cost       Cost           NSCLC   IV   NVB-P is the most cost-effective regimen at conventional thresholds of cost-effectiveness. Gem is most cost-effective when QoL is considered   (58)  2000   DA   Imaging and bx strategies to work up adrenal masses   Cost       Cost           NSCLC   Resectable   Unenhanced CT using a 10 H threshold, followed by magnetic resonance imaging if needed, was the most cost-effective strategy   (211)  1999   RC   Transbronchial needle aspiration   Cost       Cost   99         Both   Resectable   No economic methods given; $27 335 in subsequent procedures estimated to be averted   (70)  1998   RC   Bronch   Record audit   Survey     Quality   2238         Both   All   Variation in histologic distributions may be due to pathologic interpretation   (212)  1998   RC   Usual care   Record audit       Quality   1142   34       Both   All   Median time from first contact to management decision was 18 days; however, time to surgery was 63 days and time to RT was 70 days   (66)  1996   RC   Usual care   Record audit       Quality   312   65   33     SCLC   All   Elderly patients were more likely to get suboptimal care   (71)  1996   PC   Usual care         Quality   622   68   33     Both   All   Substantial variation in referral patterns, diagnostic work-up, and management   (67)  1995   RC   Usual care         Quality   5205   > 65   31   19   NSCLC   All   The elderly are less likely to be treated by all modalities at all stages   (213)  1997   RC   Usual care   Record audit       Quality   107         NSCLC   All   Overuse of testing. Otherwise good compliance with guidelines   (72)  2000   RC   chemo   Administrative data       Quality   6308   74   37   16   NSCLC   IV   Substantial unexplained variation in the use of chemo based on race, geography, and socioeconomic status   (214)  2000   Cross-section           Quality   868   69   30     NSCLC   All   Describes the proportion of patients treated in different ways   (68)  2000   PC           Quality   2182   61   42   18   NSCLC   IV   SUPPORT: older patients get less care   (73)  2000   Cross-section     Survey       Quality   9200         NSCLC   All   Medical oncologists more likely than radiation oncologists to recommend combined modality therapy for stage III disease, emphasizing the importance of multidisciplinary decision making   (69)  1999   RC   Surgery   Administrative data       Quality   10 984   > 65   32   8   NSCLC   I and II   Black patients less likely than white patients to undergo surgery, resulting in inferior survival   (74)  2000   Non-RCT   Computerized QoL surveys in clinic   EORTC QLC-C30   Patient Satisfaction Questionnaire     Satisfaction   53   65   10     Both   All   QoL surveys resulted in more symptoms being addressed. Satisfaction was high and similar in both groups   (75)  1999   PC     Treatment trade-off interview       Satisfaction   21   65   55     Both   All   57% wanted an active or collaborative role in treatment in decisions. There was a discrepancy between desired and actual role in 29%   (215)  1998   Cross-section     Interviews       Decision   81   65   33     NSCLC   IIIB and IV   Median threshold 3-mo survival benefit for mild toxicity, 9 mo for moderate. Wide variation, but only 22% would take chemo for 3-mo benefit (all were previously treated)   (216)  1997   Cross-section     Interviews       Decision   56   69   19     Both   All   Wide variation in threshold for taking chemo along with RT for locally advanced disease. Nurse were less likely to take multimodality treatment   (217)  1998   Cross-section     Interviews       Decision   56   69   19     Both   All   This interview method is feasible and reliable   (218)  1997   DA   chemo-RT vs. RT alone         Decision           NSCLC   Locally advanced   Patient preferences are important for deciding about multimodality treatment   (219)  2000   RC   RT         Decision   242   57   8     NSCLC   All   A decision support system with a prognostic index can help decide which patients to treat radically and which to treat palliatively   (220)  2000   Cross-section   chemo for unresectable NSCLC   Questionnaire       Decision   247   65   13     NSCLC   All   The choice whether to take chemo is difficult for patients, compared with students or health care providers, and is independent of how optimistically the information is presented   (221)  2000   PC   POMS         Decision   939   63   38   16   Both   IV   SUPPORT: LC patients were more likely to want comfort care only, without mechanical ventilation, than chronic obstructive pulmonary disease patients. Still, they experienced substantial dyspnea and pain   (222)  2000   PC   Interviews         Decision   747   64   35   15   Both   IV   SUPPORT: patients prefer comfort care as death approaches. Still, they often suffer from pain and confusion   (223)  1997   PC   Usual care   Interviews   Self-administered questionnaire for MDs   Communication   100   65   25       Both   All   Many patients do not understand their situation very well   (224)  1993   Cross-section   Usual care   Interviews       Communication   50   63   36     Both   All   Patients want to be told their diagnoses truthfully and want information about the disease and prognosis   (225)  1998   Cross-section   RT CHART, conventional   Interviews       Communication   24   62   33   7   NSCLC   I-IIIB   Patients wanted more information on side effects   Reference No.   Year   Design   Intervention   Measure 1   Measure 2   Measure 3   Outcome   n   Age, y   F   Nonwhite   Histology   Stage   Result   *ACE = doxorubicin (Adriamycin), cyclophosphamide, and etoposide; ATP = adenosine 5′ -triphosphate; AUC = area under the curve; bronch = bronchoscopy; BSC = best supportive care; bx = biopsy; CAP = cyclophosphamide, doxorubicin, and cisplatin; Carbo = carboplatin; CARES-SF = Cancer Rehabilitation Evaluation System—Short Form; CAV = cyclophosphamide, doxorubicin (Adriamycin), and vincristine; CDI = Clinical Dyspnea Index; CEA = cost-effectiveness analysis; CHART = continuous hyperfractionated accelerated radiation therapy; chemo = chemotherapy; CMA = cost-minimization analysis; CODE = cisplatin, vincristine, doxorubicin, and etoposide; CT = computed tomography; CUA = cost-utility analysis; cyclo = cyclophosphamide; DA = decision analysis; EORTC LC13 = European Organization for Research and Treatment of Cancer Lung Cancer 13-item module; EORTC QLQ-C30 = EORTC Quality of Life Questionnaire 30-item core instrument; EP = etoposide plus cisplatin; EUS = endoscopic ultrasound; F = proportion of females in the study sample; FACT-G = Functional Assessment of Cancer Therapy—general instrument; FACT-L = FACT lung cancer module; FDG = fluorodeoxyglucose; FLIC = Functional Living Index—Cancer; FNA = fine-needle aspiration; fx = fractions of radiotherapy; G-CSF = granulocyte colony-stimulating factor; Gem = gemcitabine; H = Hounsfield units; HADS = Hospital Anxiety and Depression Scale; HUI = Health Utility Index; I = ifosphamide; IA = ifosphamide plus doxorubicin (Adriamycin); ICE = ifosphamide, carboplatin, and etoposide; IEP = ifosphamide, epirubicin, and cisplatin; IV = intravenous; LASA = Linear Analogue Self-Assessment; LC = lung cancer; LCSS = Lung Cancer Symptom Scale; LOS = length of stay; M = mitomycin C; MD = physicians; mede = mediastinoscopy; MIP = mitomycin, ifosphamide, and cisplatin; MRC = British Medical Research Council; MVP = mitomycin, vinblastine, and cisplatin; n = sample size; NSCLC = non-small-cell lung cancer; NVB = vinorelbine; P = cisplatin; PAIS = Psychosocial Adjustment to Illness Scale; PC = prospective cohort; PCI = prophylactic cranial irradiation; PET = positron emission tomography; Ph = phase; po = oral; POMS = Profile of Mood States; PR = partial tumor response; PRQ = Personal Resource Questionnaire; PRUI = Pneumoconiosis Research Unit Index; QLCL-E4 = Quality of Life Checklist—Enjoyment, Four Questions; QLI = Quality of Life Index; QoL = quality of life; RC = retrospective cohort; RCT = randomized controlled trial; RR = response rate; RSC = Rotterdam Symptom Checklist; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SCL-90 = Symptom Checklist—90; SCLC = small-cell lung cancer; SIP = Sickness Impact Profile; SSQ = Subjective Significance Questionnaire; STAI = State-Trait Anxiety Inventory; Taxol = paclitaxel; SUPPORT = Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments; UNC = University of North Carolina; VATS = video-assisted thoracoscopy; VBL = vinblastine; VDS = vindesine; VNSSL = video-assisted non-rib spreading lobectomy; VP = vindesine and cisplatin; VP-16 = etoposide; YAG = yttrium laser.   (22)  1999   RCT   NVB vs. BSC   EORTC QLQ-C30   EORTC LC13     Qol   154   > 70   13     NSCLC   IIIB and IV   Stopped early because of poor accrual. NVB increased survival and overall QoL   (106)  1998   RCT   CHART vs. conventional RT   RSC   HADS     QoL   356   65   23     NSCLC   I-IIIB   Transient esophagitis with CHART, but otherwise similar QoL   (81)  1998   PC   RT (CHART, conventional)   RSC   HADS     QoL   2300   65   23     Both   I-IIIB   More consistency when instruments administered by trained staff   (40)  1998   RCT   Taxol-P vs. teniposide-P   EORTC QLQ-C30   EORTC LC13     QoL   317   59   30     NSCLC   IIIA-IV   Taxol better at 6 wk; effect lost at 12 wk   (107)  1998   PC   CAV/EP vs. CODE   EORTC QLQ-C30   SSQ     QoL   111   58       SCLC   Extensive   SSQ used to define small, moderate, or large changes in the EORTC QLQ-C30   (108)  1997   RCT   CAV/EP vs. po VP-16   RSC   MRC daily diary card     QoL   155   67   46     SCLC   All   po VP-16 had inferior survival and QoL   (109)  1996   RCT   EP +/- megace   LASA       QoL   252     40     SCLC   Extensive   Megace resulted in decreased response and survival, similar QoL   (110)  1994   RCT   EP +/- hydrazine   FLIC       QoL   237     32     NSCLC   IIIB and IV   Survival trend worse with hydrazine, similar QoL   (24)  1994   RCT   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Survival similar with hydrazine, but QoL worse (e.g., neutropenia)   (111)  1999   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Pain predicted survival better than did overall QoL   (90)  1997   PC   VBL-P +/- hydrazine   EORTC QLQ-C30   EORTC LC13   Duke-UNC Social Support Scale   QoL   266   61   28   15   NSCLC   IIIB and IV   Although it did not change the outcome of the trial, QoL assessment added understanding of the patients' perspective on toxicity, etc.   (41)  1999   Ph II   96-h Taxol   FACT-G   FACT-L     QoL   13   56   61     NSCLC   IIIB and IV   Only 3 of 13 patients were able to complete 3 questionnaires because of progressive disease   (42)  1998   Ph II   MVP   EORTC QLQ-C30   EORTC LC13     QoL   50   66   34     SCLC   All   QoL improved from baseline   (78)  1994   PC   Megace   EORTC QLQ-C30   QLCL-E4 (enjoyment)     QoL   20         NSCLC     Fatigue, appetite, among others, correlate better with overall QoL than does weight gain   (82)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30       QoL   100         NSCLC   I-IIIB   Only 34% completed questionnaires. QoL better with lobectomy than with pneumonectomy   (54)  1997   PC   RT for NSCLC   RSC   HADS     QoL   98         NSCLC     Used factor analysis to map RSC and HADS onto EuroQoL and HUI for utility determination   (112)  1996   PC   chemo   Holmes QoL checklist   STA1     QoL   50   58       NSCLC   IIIA-IV   Anxiety levels and personality type correlate with QoL effects   (79)  1996   PC   Resection of early-stage NSCLC   EORTC QLQ-C30   Spitzer Index     QoL   52   52   27     NSCLC     QoL is restored 3-6 mo after surgery   (113)  1998   Ph II   ICE   MRC daily diary card       QoL   30   60   57     SCLC   All   QoL satisfactory, but worse on the first day of each cycle   (19)  1997   PC   chemo   LCSS       QoL   673   61   32     NSCLC   IIIA-IV   Frequent QoL measurements are needed, and AUC may be useful   (43)  1998   RCT   Carbo + VP-16   EORTC QLQ-C30   EORTC LC13     QoL   150   64   41     NSCLC   IIIB and IV   The chemotherapy resulted in improved survival and QoL   (23)  1998   Ph I   Carbo + po VP-16   LCSS       QoL   46   > 70   15     NSCLC   IIIB and IV   QoL improved in 41% and was a better predictor of survival than was response   (83)  1997   RC   RT for NSCLC   LCSS       QoL   63   67   15     NSCLC   All   RT appears to have improved QoL   (26)  1997   Ph II   Taxol by 3-h infusion   FACT-G   FACT-L     QoL   20   63   45     NSCLC   IV   Baseline QoL predicted response, but changes in QoL did not correlate with response   (20)  1997   Ph II   3-h Taxol + Carbo   FACT-G   FACT-L     QoL   11   65   0   27   NSCLC   IIIA-IV   QoL improved in most patients   (114)  1997   Randomized Ph II   Carbo + Taxol 175 vs. 225 mg/m2  EORTC QLQ-C30       QoL   49   61   14     NSCLC   IIIA-IV   No difference in QoL   (115)  1997   Ph II   Taxol by 3-h infusion   RSC   HADS     QoL   21   55   25     NSCLC   IIIA-IV   Treatment well tolerated. High completion rate for QoL forms   (21)  1996   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Patients with poor prognostic features had worse QoL at baseline, but more improvement with chemo   (35)  1992   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   459     10     NSCLC   All   Mean compliance 49%. Institution strongly predicted compliance   (27)  1995   PC   Usual care   Likert Symptom Scale       QoL   82   64   39     Both   All   Increased symptom distress with advanced disease, young age, and women. QoL predicted survival   (84)  1995   RCT   CAV vs. Carbo + teniposide   EORTC QLQ-C30       QoL   59   58   8     SCLC   Extensive   CAV yielded better survival, equal QoL   (116)  1995   RCT   Weekly EP/IA vs. 3 weekly EP/CAV   MRC daily diary card       QoL   75   62   36     SCLC   All   No difference in survival. QoL better on 3-weekly treatment (every 3 wk)   (117)  1994   PC   Usual care   Hassles Scale   Demands of Illness Inventory   PRQ, PAIS   QoL   56   60   38   16   Both   IIIA-IV   Black patients and patients with more demands of illness had worse psychosocial adjustment   (118)  1994   Ph II   Fotemustine   Spitzer Index       QoL   77   60   14     NSCLC   All   17% RR. QoL stable   (98)  1994   PC   Usual care   LCSS       QoL   207         NSCLC   All   LCSS was feasible, reliable, and valid   (76)  1993   PC   Usual care   EORTC QLQ-C30       QoL   305   63   24     Both   All   EORTC QLQ-C30 was feasible, reliable, and valid   (96)  1993   PC   Usual care   LCSS       QoL   121   59   33     Both   All   LCSS was feasible, reliable, and valid   (119)  1996   PC   Usual care   Interviews       QoL   200   66   44     Both   All   Family life, health, and social life were most important to patients. Family and social life are missed by most QoL instruments   (15)  1993   PC   Usual care   Symptom Distress Scale   CARES-SF     QoL   69   61   100     Both   All   Pain, fatigue, and insomnia were strongly correlated in women with LC   (120)  1992   Cross-section   Usual care   Spiritual Health Inventory       QoL   23     30   8   Both   All   Patients had moderately high levels of spiritual health, but nurses were poorly able to determine this   (25)  1991   RCT   Planned vs. “as required” chemo   MRC daily diary card       QoL   300   65   25     SCLC   All   Survival similar, but patients with planned treatment had better QoL   (18)  1991   PC   Palliative RT   EORTC QLQ-C30   MRC General Condition Scale   MRC Dyspnea Grade   QoL   40   68   18     NSCLC   IIIA-IV   MDs were poor at predicting QoL but were good at detecting changes   (121)  1991   RCT   Maintenance chemo vs. none after 6 mo   MRC daily diary card       QoL   369         SCLC   Limited   Similar survival, better QoL with maintenance chemo   (28)  1991   PC   Usual care   FLIC       QoL   40   62   13   38   NSCLC   IV   QoL predicts survival   (44)  1990   RCT   PCI   MRC daily diary card   EORTC QLQ-C30   Spitzer Index   QoL   53   63   30     SCLC   All   Diaries are reliable and valid. QoL worsens with successive chemo and PCI   (122)  1990   Ph I/II   Cyclo + trimetrexate   LASA       QoL   55   58   1     NSCLC   All   Testing of 9 domains feasible. Stable QoL despite only 4% PR   (123)  1997   Cross-section   Usual care   SF-36       QoL   590   72   48     Both   All   Also had lung, colon, and prostate cancer patients: LC patients were the most debilitated   (124)  1993   Cross-section   Usual care   Interviews   PAIS     QoL   61   60   33   14   Both   All   No relationship between perceived control and psychosocial adjustment   (29)  1994   PC   Various   FLIC       QoL   438         Both   All   QoL predicts survival   (91)  1996   PC   chemo   EORTC QLQ-C30       QoL   305         Both   All   Mixed response of QoL parameters to chemo   (125)  1996   RCT   2 vs. 13 fx   RSC   HADS   MRC daily diary card   QoL   509   66   21     NSCLC   Unresectable   2 fx palliated symptoms faster, but 13 fx had better survival   (88)  1994   PC   Various   EORTC QLQ-C30   EORTC LC13     QoL   883         Both   All   Neuropathy, dyspnea, and pain sections of the instrument need further refinement   (17)  1997   PC   Usual care   Symptom Distress Scale       QoL   60   58   100   13   Both   All   Factor analysis found several clusters of distress   (126)  1994   PC   Thoracotomy   QLI   SIP   CDI, PRUI   QoL   91   63   31     NSCLC   Resectable   QoL deteriorates during the first 3 mo after surgery but improves afterward   (85)  1998   PC   Diagnosis of LC   HADS   EORTC QLQ-C30     QoL   129   68   40     Both   All   Anxiety decreases after the diagnosis of LC has been made   (127)  1994   RCT   RT to primary tumor   POMS   Clinician-completed rating scale   Trail Making B Test   QoL   119   59   33   7   SCLC   Limited   RT improved survival but decreased QoL and distress   (16)  1993   PC   Usual care   CARES-SF   Symptom Distress Scale     QoL   69   61   100   14   Both   All   QoL was predicted most by symptom distress, physical functioning, and recurrence   (31)  1995   PC   Usual care   HADS   RSC   Spitzer Index   QoL   40   60   20     Both   All   Brief QoL scales correlated well with these formal measures, but not with overall QoL   (128)  1992   PC   chemo   Cancer Inventory of Problem Situations       QoL   36   66   19     SCLC   All   QoL improved with chemo   (33)  1991   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   Improvement on the QoL scales correlated with response to treatment   (89)  1992   PC   chemo   EORTC QLQ-C30   SIP   HADS   QoL   62   66   29     SCLC   All   The EORTC questionnaire performed well, except for emotional and social functioning   (129)  1998   RCT   IEP vs. MVP vs. BSC   FLIC   QLI     QoL   107   57       NSCLC   IV   The chemo resulted in improved survival, without a decrease in QoL   (130)  1993   PC   Usual care   Symptom checklist       QoL           Both   All   Checklists draw attention to problems and can be followed over time   (131)  1992   Cross-section   Usual care   Interviews       QoL   30   61   50     Both   All   Caregivers can serve as proxies for patients, but they tend to underestimate physical function   (132)  1992   Cross-section   Usual care   FLIC   Investigator-designed questionnaire     QoL   64   61   23     Both   All   Good reliability and validity for Japanese translation of the FLIC. Cancer patients scored lower than 50 noncancer patients, especially in mood, anxiety, relationships, and physical function   (133)  1999   PC   Usual care   Investigator-developed diary   LASA     QoL   53   62   17     Both   II-IV   Japanese diary form was reliable and valid   (134)  1995   PC   BSC vs. IEP vs. MVP   FLIC   QLI     QoL   118   56   30     NSCLC   IIIB and IV   Thai modifications (T-FLIC and T-QLI) correlated well with each other and Karnofsky performance status   (30)  1998   Ph II   MIP   LASA       QoL   38   38   21     NSCLC   IIIB and IV   39% RR; 58% improved QoL. QoL predicted survival   (135)  1996   PC   Usual care   Locus of control   Symptom checklist     QoL   31   58   13     Both   All   Patients have a more internal locus of control than non-cancer patients. Locus of control and QoL were not related   (136)  1996   Case-control   Usual care   Nottingham Health Profile   EORTC QLQ-C30   EORTC LC13   QoL   232   66   44     Both   All   Interviewer-administered QoL instruments were acceptable and even enjoyable to most patients   (99)  1999   PC   chemo   LCSS       QoL   673   59   32   17   NSCLC   IIIA-IV   Normative scores for this population are presented   (94)  1995   PC   Usual care   FACT-G   FACT-L     QoL   116   60   53   25   Both   All   Test-retest reliability is demonstrated   (32)  1995   PC   Usual care   Therapy Impact Questionnaire       QoL   128   64   7     Both   All   Patient perception of QoL predicted survival   (137)  1994   Cross-section   Usual care   CARES-SF   LASA     QoL   57   62   44   7   Both   Survivors   LC survivors have poorer QoL than colon or prostate cancer survivors   (77)  1994   PC   chemo   EORTC QLQ-C30       QoL   160   58       Both   All   The instrument is sensitive to the effects of chemo administration and tumor stage   (36)  1994   RCT   chemo   RSC   HADS     QoL   310     37     SCLC   All   Explored ways of dealing with attrition and missing information   (97)  1994   PC   chemo   LCSS   Brief Symptom Inventory   SCL-90, POMS, SIP   QoL   144   59       NSCLC   IIIA-IV   Confirmed construct validity   (138)  1993   PC   chemo   EORTC QLQ-C30   Bf-S (emotional)   LASA   QoL   127         SCLC   All   Fatigue and malaise are important predictors of QoL   (139)  2000   Cross-section   PET vs. mede for staging   Numerical rating scale       QoL   23   57       NSCLC   All   Patients prefer noninvasive staging. Disease extent is the major determinant of utility   (140)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   Clinical benefit     QoL   207   59   18     NSCLC   IIIB and IV   Survival favored docetaxel. Nausea, pain, and dyspnea improved with docetaxel, with a trend toward improved global QoL   (141)  1999   RCT   Gem vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   147   59   23     NSCLC   IIIA-IV   No difference between arms in survival or QoL, although less toxicity in Gem arm   (142)  2000   PC   None   Symptom Distress Scale   Thurstone scale     QoL   26   66   50     Both   All   Fatigue was the most intense symptom, but it ranked second last on the Thurstone scale   (143)  1999   PC   None   Freiburg Questionnaire of Coping With Illness   A uniquely developed Depression Scale   QoL   103   59   17       Both   All   Depressive coping and emotional distress correlate with shorter survival   (37)  1999   Ph II   Gem   EORTC QLQ-C30   EORTC LC13     QoL   30   59   10     NSCLC   IIIB and IV   20% RR. Cough was the only aspect of QoL that changed substantially, improving after 3 cycles   (144)  2000   PC   Palliative RT   EORTC QLQ-C30   EORTC LC13     QoL   69         NSCLC   All   QoL, especially dyspnea and social functioning, improved in those with objective tumor response   (145)  2000   PC   High-dose palliative RT   EORTC QLQ-C30       QoL   42   70       Both   All   Patients had improved QoL after treatment. Regression models were fitted on the basis of both time since treatment and time left to live   (146)  2000   Ph I/II   High-dose EP   EORTC QLQ-C30   EORTC LC13     QoL   42   57   22     NSCLC   IIIA-IV   RR of 33%. QoL stable, with improved emotional status but worsening fatigue   (147)  2000   RCT   Gem vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   300   65   37     NSCLC   IIIA-IV   QoL was the main end point. Pain, cough, and fatigue all improved > 10%. There was no difference in survival. 19% PR   (38)  2000   Ph II   Gem + NVB   EORTC QLQ-C30   EORTC LC13     QoL   126   63   12     NSCLC   IIIB and IV   Dropout was a big problem   (39)  2000   Ph II   NVB   Therapy Impact Questionnaire       QoL   46   75   13     NSCLC   All   After baseline, large amounts of missing data. Patients often required help to complete questionnaires. QoL stable throughout treatment   (148)  2000   Ph II   Taxol-ifosphamide-P   LCSS       QoL   50   58   12     NSCLC   IIIA-IV   64% tumor RR. QoL improved in 74%   (149)  1999   PC   Informed consent   HADS       QoL   119   65   36     NSCLC   All   Informed consent increases anxiety and depression, especially in women and patients with poor performance status   (34)  2000   PC   RT   EORTC QLQ-C30   EORTC LC13     QoL   198     15     NSCLC   I-IIIB   Global QoL predicts survival for lymph node-positive patients   (150)  2000   PC   Usual care   SF-36   Symptom Experience Scale     QoL   129   72   42   5   Both   All   Younger patients, patients with higher previous physical function, and patients with more current symptoms experienced greater loss of function   (151)  1999   PC   RT   Quality adjusted survival time       QoL   979         NSCLC   II-IIIB   Two authors chose weights for different toxic effects and calculated Q time for different therapies based on prior RTOG studies   (152)  2000   RCT   Taxol vs. BSC   RSC       QoL   157   64   25     NSCLC   IIIB and IV   Functional ability improved with Taxol. Otherwise, no difference   (153)  2000   RCT   ATP vs. BSC   RSC       QoL   58   62   35     NSCLC   IIIB and IV   QoL deteriorated in the control group but not in the ATP group   (154)  2000   RCT   Docetaxel vs. BSC   EORTC QLQ-C30   RSC     QoL   104   61   31     NSCLC   IIIB and IV   QoL will be reported separately: less worsening in docetaxel arm   (155)  2000   PC   Usual care   HADS   RSC     QoL   1189         Both   Advanced   Depression more common in SCLC patients, among women, and in more debilitated patients   (95)  2000   RCT   Taxol-P vs. EP   FACT-G   FACT-L     QoL   599   62   36   13   NSCLC   IIIB and IV   Trend toward improved QoL on the Taxol arm   (156)  2000   RCT   ACE every 2 wk with G-CSF vs. ACE every 3 wk   RSC       QoL   403   61   42     SCLC   All   Survival was improved with similar QoL in the intensively treated patients   (157)  1999   RCT   Gem-P vs. MIP   EORTC QLQ-C30   EORTC LC13     QoL   307   61   24     NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR with similar QoL, survival, and time to disease progression   (86)  1999   RCT   MIP vs. BSC   EORTC QLQ-C30   EORTC LC13     QoL   820   64   25     NSCLC   IIIA-IV   MIP improved survival with improved QoL   (158)  1999   RCT   Gem-P vs. EP   EORTC QLQ-C30   EORTC LC13     QoL   135   59   7   1   NSCLC   IIIB and IV   Patients treated with Gem-P had a higher RR and delayed disease progression; QoL was similar   (159)  2000   RCT   Gem-NVB vs. NVB   LCSS       QoL   120   75   6     NSCLC   IIIB and IV   Gem-NVB improved survival and time to symptomatic progression; only 40% had a decrease in QoL compared with 60% receiving NVB alone   (160)  1999   PC   VATS vs. open thoracotomy   Symptom questionnaire (unique)       QoL   44   62   36     NSCLC   Resectable   VATS resulted in decreased pain and increased satisfaction with the wound   (161)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CEA       Cost     51       Both   All   Open bx is most cost-effective   (45)  1993   RC   Restage responding patients with scans or bronch   CEA       Cost   324   62   45     SCLC   Limited   Restaging is not cost-effective   (162)  1996   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (163)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (164)  1998   DA   FDG-PET for staging   CEA       Cost           NSCLC   All   FDG-PET is a cost-effective addition to LC staging   (165)  1993   RC   VATS vs. open thoracotomy   CMA       Cost   150   63   57     NSCLC   All   Trend toward decreased operating time and LOS for VATS despite higher equipment costs   (166)  1997   DA   FNA for patients with a history of cancer   CEA       Cost           Both   All   FNA with selected use of thoracoscopy is most cost-effective   (167)  1995   RCT   CT vs. mede   CEA       Cost   685   64   29     NSCLC   Resectable   CT is more cost-effective than mede   (46)  1995   DA   Head CT for staging disease in patients with no neurologic symptoms   CEA       Cost           Both   All   CT head is not cost-effective   (168)  1996   DA   Cytologic brushings for bronchoscopically visible tumors   CEA       Cost           NSCLC   All   Either washings or brushings, but not both, are cost-effective   (53)  1997   DA   Sputum cytology, FNA, bronch, or open bx   CUA       Cost           Both   All   For patients averse to waiting, thoracoscopy is most cost-effective; for those averse to morbidity, expectant waiting is best   (169)  1993   RC   Sequence of staging tests   CMA       Cost   451         SCLC   All   The algorithm can save one-third of costs as long as testing is stopped as soon as metastases are detected   (170)  1998   DA   Diagnosis of LC   CEA       Cost           Both   All   Open bx is most cost-effective in operative candidates; sputum is least   (47)  1998   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Routine use of G-CSF is not cost-effective   (171)  1999   DA   Radon screening and mitigation to prevent LC   CEA       Cost           Both   All   Limiting testing to high-risk geographical areas and requiring a confirmatory test before mitigation are most cost-effective   (172)  1999   RC   Usual care   Cost       Cost   253   71       Both   All   Costs were less than those for Canadian studies because of less aggressive intervention   (173)  1994   RC   Usual care   Cost       Cost   300         Both   All   A “top-down” cost allocation approach is feasible   (174)  1993   RCT   G-CSF during chemo   CMA       Cost   68         SCLC   All   G-CSF could save money in patients at high risk of febrile neutropenia   (48)  1996   DA   Follow-up after curative resection   CMA       Cost           NSCLC   All   There was a fivefold difference in the cost of follow-up strategies, with no evidence of difference in benefit   (175)  1991   RC   Usual care   Cost       Cost   15 381   > 65       Both   All   LC cost $12 510 1984 U.S. dollars   (176)  1996   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost           NSCLC   IIIB and IV   NVB-P was effective and cost-effective   (49)  1999   DA   Conformal vs. standard RT   CMA       Cost           Both   All   Conformal RT was twice as expensive as standard   (177)  1990   PC   chemo   Hospital days       Cost   90     25     SCLC   All   Average 18 days in hospital: 69% of hospital days due to tumor complications   (59)  1996   PC   Gem vs. VP-P vs. VP-I   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (60)  1996   PC   Gem vs. VP-P   CMA       Cost   249   60   27     NSCLC   IIIA-IV   Gem was cost-saving compared with other regimens if drug costs were excluded   (178)  1995   DA   Gem vs. VP-I   CMA       Cost           NSCLC   IIIA-IV   Excluding drug costs. Gem used fewer resources   (179)  1996   RC   P + either VP-16 or VP-16 phosphate   CMA       Cost   254         SCLC   All   VP-16 phosphate, a prodrug of VP-16 with shorter administration time, consumes fewer resources   (180)  1997   DA   Multimodality treatment   CEA       Cost           NSCLC   III   Multimodality therapy is cost-effective   (181)  1997   DA   Taxol vs. BSC   CEA       Cost           NSCLC   IV   Taxol is cost-effective   (182)  1999   DA   Taxol-P vs. BSC   CEA       Cost           NSCLC   IV   Taxol-P is cost-effective   (183)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (184)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (185)  1995   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (186)  1996   DA   Usual care   Cost       Cost           Both   All   Hospitalization is the main driver of LC costs   (187)  1993   RC   chemo   CMA       Cost           SCLC   All   Large variation in the cost of regimes with similar efficacy   (188)  1996   DA   NVB vs. NVB-P vs. VP-16-P vs. VBL-P vs. BSC   CEA       Cost           NSCLC   IV   VBL-P is most cost-effective, but NVB-P is most effective and is cost-effective when given in an outpatient setting   (189)  1996   DA   Gem vs. BSC   CEA       Cost           NSCLC   IV   Gem is more costly but is still cost-effective   (190)  1998   RC   Usual care   Cost       Cost   336   <65       NSCLC   All   Type of treatment predicted total cost more than did hospital days   (191)  1990   RCT   CAP vs. VP vs. BSC   CEA       Cost   137         NSCLC   IIIB and IV   The chemo was both effective and cost-effective. In fact, CAP actually saved money   (50)  1995   RCT   CAP vs. VP vs. BSC   CUA       Cost   137         NSCLC   IIIB and IV   Did not confirm the cost-savings found by Jaakkimainen et al. (65) but did find chemo to be cost-effective   (51)  1994   RC   G-CSF during chemo   CMA       Cost   137   62   47     SCLC   All   G-CSF was not cost-effective   (192)  1996   DA   Gem-P vs. NVB-P vs. VP-16-P vs. MIP   CEA       Cost           NSCLC   IIIB and IV   Gem-P had the lowest cost per response   (193)  1992   RC   Usual care   Cost       Cost   39   68       SCLC   All   Hospitalization and chemo drug costs were the main drivers of SCLC costs. QoL did not suffer with intensive chemo   (194)  1995   RCT   NVB vs. NVB-P vs. VDS-P   CEA       Cost   612         NSCLC   IIIA-IV   As long as NVB's toxicity profile is acceptable, it is effective and cost-effective   (195)  1996   RCT   M-NVB-P vs. M-VDS-P   CEA       Cost   209   61   5     NSCLC   IIIA-IV   M-NVB-P costs less per response   (55)  1997   RCT   CHART vs. conventional RT   CEA       Cost   284   65   21     NSCLC   I-IIIB   CHART more costly but likely cost-effective, given the survival benefits   (56)  1998   DA   Gem vs. EP vs. IE   CMA       Cost           NSCLC   IIIB and IV   Gem cost-saving   (196)  1996   DA   G-CSF during chemo   CEA       Cost           SCLC   All   Based on a meta-analysis showing no survival benefit but reduced incidence of neutropenic fever, G-CSF would have to cost $395-$569 per cycle to be cost neutral   (197)  1992   RCT   po vs. IV VP-16 with P   CMA       Cost   83         SCLC   All   The oral regimen was less costly and equally efficacious   (198)  1995   Ph II   Fazarabine   CMA       Cost   23   65   39     NSCLC   IV   Fazarabine had no activity (0% RR) and similar costs to VP-16-P   (199)  1998   RC   Usual care   Cost       Cost   554   <65   43     Both   All   Hospital charges ≈$35 000 in the last year of life   (200)  1998   RC   VATS vs. open thoracotomy   Cost       Cost   80   56   33     NSCLC   I   VATS wedge resection was less costly, but VATS lobectomy was more costly than the open procedure   (201)  2000   Cross-section   PET added to staging work-up   Questionnaire       Cost   87   55   16     Both   All   Willingness to pay for PET ranged from $1500 to $4000, proportional to perceived risk of cancer and income. Insured vs. Medicaid willing to pay more   (202)  2000   RC   Ph II chemo trials   Cost       Cost   43         Both   IV   The cost of doing Ph II studies is more for a drug that works, as it is given longer, and is driven by imaging studies and laboratory tests. The cost was still less than standard therapy   (203)  2000   RCT   Gem-P vs. VP-16-P   Cost       Cost   135   58   7     NSCLC   IV   Survival was equivalent, although RR and time to progression were superior for Gem-P. Increased cost of the drugs was offset by decreased hospitalization   (62)  2000   RCT   YAG vs. YAG + brachytherapy         Cost   29   61   21     NSCLC   All   Brachytherapy saved money by decreasing the need for repeat procedures. No method described   (52)  2000   DA   Adding PET to chest CT         Cost   56         NSCLC   All   PET unlikely to be a cost-effective addition to the diagnostic work-up in Japan (although it seems to easily meet U.S. standards of cost-effectiveness)   (63)  1999   Case series   VNSSL   Cost       Cost   250     52     Both   Resectable   VNSSL appears efficacious, costs ≈50% of open thoracotomy. No method described   (204)  1999   RCT   Taxol-P vs. teniposide-P   Cost       Cost   62         NSCLC   IV   Taxol-P had a higher RR, at a cost of $21 011 per response   (205)  2000   RC   Follow-up after curative resection   Survival   Cost     Cost   245   64   41     NSCLC   I and II   Most recurrences are found by the family doctor and have equivalent survival to that found by the surgeon. Costs would be 75% less if family doctors did all follow-up, and the results the same   (206)  2000   RCT   Pleural tent after lobectomy   Cost       Cost   50   67   20     NSCLC   Resectable   Pleural tenting reduced air leak, hospital days, and costs   (207)  1999   RC   Staging for early-stage disease   Cost       Cost   755   63   39     NSCLC   I   Metastases were found in only 2.1% of T1N0 and 5.4% of T2N0 tumors. Total cost of unnecessary tests was $924 168   (208)  2000   RCT   CT scan before bronch   Cost       Cost   171   67   38     NSCLC   Resectable   CT averted many invasive procedures, resulting in a lower cost per patient   (209)  1999   DA   EUS/FNA vs. mede   Cost       Cost           NSCLC   Resectable   Despite a lower negative predictive value, EUS was less costly   (57)  1999   DA   Radon screening and mitigation   Cost       Cost           Both   All   Radon remediation is cost-effective from all perspectives in preventing LC   (64)  2000   Case series   Accelerated hyperfractionation   Medicare schedule       Cost   29   68   41     NSCLC   IB-IIIB   Costs only presented in “Discussion” section. Tolerated well, and costs not excessive compared with conventional treatment   (210)  2000   DA   chemo   Cost       Cost           NSCLC   IV   NVB-P is the most cost-effective regimen at conventional thresholds of cost-effectiveness. Gem is most cost-effective when QoL is considered   (58)  2000   DA   Imaging and bx strategies to work up adrenal masses   Cost       Cost           NSCLC   Resectable   Unenhanced CT using a 10 H threshold, followed by magnetic resonance imaging if needed, was the most cost-effective strategy   (211)  1999   RC   Transbronchial needle aspiration   Cost       Cost   99         Both   Resectable   No economic methods given; $27 335 in subsequent procedures estimated to be averted   (70)  1998   RC   Bronch   Record audit   Survey     Quality   2238         Both   All   Variation in histologic distributions may be due to pathologic interpretation   (212)  1998   RC   Usual care   Record audit       Quality   1142   34       Both   All   Median time from first contact to management decision was 18 days; however, time to surgery was 63 days and time to RT was 70 days   (66)  1996   RC   Usual care   Record audit       Quality   312   65   33     SCLC   All   Elderly patients were more likely to get suboptimal care   (71)  1996   PC   Usual care         Quality   622   68   33     Both   All   Substantial variation in referral patterns, diagnostic work-up, and management   (67)  1995   RC   Usual care         Quality   5205   > 65   31   19   NSCLC   All   The elderly are less likely to be treated by all modalities at all stages   (213)  1997   RC   Usual care   Record audit       Quality   107         NSCLC   All   Overuse of testing. Otherwise good compliance with guidelines   (72)  2000   RC   chemo   Administrative data       Quality   6308   74   37   16   NSCLC   IV   Substantial unexplained variation in the use of chemo based on race, geography, and socioeconomic status   (214)  2000   Cross-section           Quality   868   69   30     NSCLC   All   Describes the proportion of patients treated in different ways   (68)  2000   PC           Quality   2182   61   42   18   NSCLC   IV   SUPPORT: older patients get less care   (73)  2000   Cross-section     Survey       Quality   9200         NSCLC   All   Medical oncologists more likely than radiation oncologists to recommend combined modality therapy for stage III disease, emphasizing the importance of multidisciplinary decision making   (69)  1999   RC   Surgery   Administrative data       Quality   10 984   > 65   32   8   NSCLC   I and II   Black patients less likely than white patients to undergo surgery, resulting in inferior survival   (74)  2000   Non-RCT   Computerized QoL surveys in clinic   EORTC QLC-C30   Patient Satisfaction Questionnaire     Satisfaction   53   65   10     Both   All   QoL surveys resulted in more symptoms being addressed. Satisfaction was high and similar in both groups   (75)  1999   PC     Treatment trade-off interview       Satisfaction   21   65   55     Both   All   57% wanted an active or collaborative role in treatment in decisions. There was a discrepancy between desired and actual role in 29%   (215)  1998   Cross-section     Interviews       Decision   81   65   33     NSCLC   IIIB and IV   Median threshold 3-mo survival benefit for mild toxicity, 9 mo for moderate. Wide variation, but only 22% would take chemo for 3-mo benefit (all were previously treated)   (216)  1997   Cross-section     Interviews       Decision   56   69   19     Both   All   Wide variation in threshold for taking chemo along with RT for locally advanced disease. Nurse were less likely to take multimodality treatment   (217)  1998   Cross-section     Interviews       Decision   56   69   19     Both   All   This interview method is feasible and reliable   (218)  1997   DA   chemo-RT vs. RT alone         Decision           NSCLC   Locally advanced   Patient preferences are important for deciding about multimodality treatment   (219)  2000   RC   RT         Decision   242   57   8     NSCLC   All   A decision support system with a prognostic index can help decide which patients to treat radically and which to treat palliatively   (220)  2000   Cross-section   chemo for unresectable NSCLC   Questionnaire       Decision   247   65   13     NSCLC   All   The choice whether to take chemo is difficult for patients, compared with students or health care providers, and is independent of how optimistically the information is presented   (221)  2000   PC   POMS         Decision   939   63   38   16   Both   IV   SUPPORT: LC patients were more likely to want comfort care only, without mechanical ventilation, than chronic obstructive pulmonary disease patients. Still, they experienced substantial dyspnea and pain   (222)  2000   PC   Interviews         Decision   747   64   35   15   Both   IV   SUPPORT: patients prefer comfort care as death approaches. Still, they often suffer from pain and confusion   (223)  1997   PC   Usual care   Interviews   Self-administered questionnaire for MDs   Communication   100   65   25       Both   All   Many patients do not understand their situation very well   (224)  1993   Cross-section   Usual care   Interviews       Communication   50   63   36     Both   All   Patients want to be told their diagnoses truthfully and want information about the disease and prognosis   (225)  1998   Cross-section   RT CHART, conventional   Interviews       Communication   24   62   33   7   NSCLC   I-IIIB   Patients wanted more information on side effects   View Large I thank Candace Canto of the National Library of Medicine for assistance with the literature search. References 1 American Cancer Society. Cancer statistics 2000. CA Cancer J Clin  2000; 50: 7 -33. Google Scholar 2 DeVita VT Jr, Hellman S, Rosenberg S. Cancer: principles and practice of oncology . 4th ed. Philadelphia (PA): Lippincott; 1993. Google Scholar 3 Reis LA, Kosary CL, Hankey BF, Miller BA, editors. SEER cancer statistics review, 1973-1996 . Bethesda (MD): National Cancer Institute; 1999. Google Scholar 4 Thatcher N, Hopwood P, Anderson H. Improving quality of life in patients with non-small cell lung cancer: research experience with gemcitabine. Eur J Cancer  1997 ; 33(Suppl 1): S8 -13. Google Scholar 5 Hollen PJ, Gralla RJ. Comparison of instruments for measuring quality of life in patients with lung cancer. Semin Oncol  1996 ; 23: 31 -40. Google Scholar 6 Hopwood P. Quality of life assessment in chemotherapy trials for non-small cell lung cancer: are theory and practice significantly different. Semin Oncol  1996; 23: 60 -4. Google Scholar 7 Manegold C, Schwarz R. Quality of life and supportive care in the treatment of NSCLC. Chest  1996 ; 109: 113S -114S. Google Scholar 8 Miettinen OS. Screening for lung cancer: can it be cost-effective. CMAJ  2000; 16: 1431 -6. Google Scholar 9 Johnson DH. Evolution of cisplatin-based chemotherapy in non-small cell lung cancer: a historical perspective and the Eastern Cooperative Oncology Group Experience. Chest  2000 ; 117(4 Suppl 1): 133S -137S. Google Scholar 10 Hillner BE. Potential evaluation of the incremental cost-effectiveness of paclitaxel in advanced non-small-cell lung cancer (Eastern Cooperative Oncology Group 5592). J Natl Cancer Inst Monogr  1995; 19: 65 -7. Google Scholar 11 Chang AY, Kim K, Boucher H, Bonomi P, Stewart JA, Karp DD, et al. A randomized phase II trial of echinomycin, trimetrexate, and cisplatin plus etoposide in patients with metastatic nonsmall cell lung carcinoma: an Eastern Cooperative Oncology Group Study (E1587). Cancer  1998 ; 82: 292 -300. Google Scholar 12 Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, et al. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol  1996; 14: 2774 -84. Google Scholar 13 Li B, Yu J, Suntharalingam M, Kennedy AS, Amin PP, Chen Z, et al. Comparison of three treatment options for single brain metastasis from lung cancer. Int.J Cancer  2000 ; 90: 37 -45. Google Scholar 14 White SC, Cheeseman S, Thatcher N, Anderson H, Carrington B, Hearn S, et al. Phase II study of oral topotecan in advanced non-small cell lung cancer. Clin Cancer Res  2000 ; 6: 868 -73. Google Scholar 15 Sarna L. Correlates of symptom distress in women with lung cancer. Cancer Pract  1993; 1: 21 -8. Google Scholar 16 Sarna L. Women with lung cancer: impact on quality of life. Qual Life Res  1993; 2: 13 -22. Google Scholar 17 Sarna L, Brecht ML. Dimensions of symptom distress in women with advanced lung cancer: a factor analysis. Heart Lung  1997 ; 26: 23 -30. Google Scholar 18 Regan J, Yarnold J, Jones PW, Cooke NT. Palliation and life quality in lung cancer: how good are clinicians at judging treatment outcome. Br J Cancer  1991; 64: 396 -400. Google Scholar 19 Hollen PJ, Gralla RJ, Cox C, Eberly SW, Kris MG. A dilemma in analysis: issues in the serial measurement of quality of life in patients with advanced lung cancer. Lung Cancer  1997 ; 18: 119 -36. Google Scholar 20 Roychowdhury DF, Desai P, Zhu YW. Paclitaxel (3-hour infusion) followed by carboplatin (24 hours after paclitaxel): a phase II study in advanced non-small cell lung cancer. Semin Oncol  1997 ; 24: S12 -37-S12-40. Google Scholar 21 Bernhard J, Hurny C, Bacchi M, Joss RA, Cavalli F, Senn HJ, et al. Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK). Br J Cancer  1996 ; 74: 1660 -7. Google Scholar 22 The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  1999 ; 91: 66 -72. Google Scholar 23 Frasci G, Comella P, Panza N, De Cataldis G, Del Gaizo F, Pozzo C, et al. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer  1998; 34: 1710 -4. Google Scholar 24 Kosty MP, Fleishman SB, Herndon JE, Coughlin K, Kornblith AB, Scalzo A, et al. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol  1994; 12: 1113 -20. Google Scholar 25 Earl HM, Rudd RM, Spiro SG, Ash CM, James LE, Law CS, et al. A randomised trial of planned versus as required chemotherapy in small cell lung cancer: a Cancer Research Campaign trial. Br J Cancer  1991 ; 64: 566 -72. Google Scholar 26 Tester WJ, Jin PY, Reardon DH, Cohn JB, Cohen MH. Phase II study of patients with metastatic nonsmall cell carcinoma of the lung treated with paclitaxel by 3-hour infusion. Cancer  1997 ; 79: 724 -9. Google Scholar 27 Degner LF, Sloan JA. Symptom distress in newly diagnosed ambulatory cancer patients and as a predictor of survival in lung cancer. J Pain Sympt Manage  1995; 10: 423 -31. Google Scholar 28 Ganz PA, Lee JJ, Siau J. Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer  1991 ; 67: 3131 -5. Google Scholar 29 Ruckdeschel JC, Piantadosi S. Quality of life in lung cancer surgical adjuvant trials. Chest  1994 ; 106: 324S -328S. Google Scholar 30 Han JY, Kim HK, Choi BG, Moon H, Hong YS, Lee KS. Quality of life (QOL) assessment of MIP (mitomycin, ifosphamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC). Jpn J Clin Oncol  1998 ; 28: 749 -53. Google Scholar 31 Abratt R, Viljoen G. Assessment of quality of life by clinicians—experience of a practical method in lung cancer patients. S Afr Med J  1995; 85: 896 -8. Google Scholar 32 Buccheri GF, Ferrigno D, Tamburini M, Brunelli C. The patient's perception of his own quality of life might have an adjunctive prognostic significance in lung cancer. Lung Cancer  1995 ; 12: 45 -58. Google Scholar 33 Bergman B, Sullivan M, Sorenson S. Quality of life during chemotherapy for small cell lung cancer. I. An evaluation with generic health measures. Acta Oncol  1991 ; 30: 947 -57. Google Scholar 34 Langendijk H, Aaronson NK, de Jong JM, ten Velde GP, Muller MJ, Wouters M. The prognostic impact of quality of life assessed with the EORTC QLQ-C30 in inoperable non-small cell lung carcinoma treated with radiotherapy. Radiother Oncol  2000; 55: 19 -25. Google Scholar 35 Hurny C, Bernhard J, Joss R, Willems Y, Cavalli F, Kiser J, et al. Feasibility of quality of life assessment in a randomized phase III trial of small cell lung cancer—a lesson from the real world—the Swiss Group for Clinical Cancer Research SAKK. Ann Oncol  1992 ; 3: 825 -31. Google Scholar 36 Hopwood P, Stephens RJ, Machin D. Approaches to the analysis of quality of life data: experiences gained from a medical research council lung cancer working party palliative chemotherapy trial. Qual Life Res  1994; 3: 339 -52. Google Scholar 37 Gridelli C, Perrone F, Gallo C, Rossi A, Barletta E, Barzelloni ML, et al. Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial. Anticancer Res  1999; 19: 4535 -8. Google Scholar 38 Gridelli C, Frontini L, Perrone F, Gallo C, Gulisano M, Cigolari S, et al. Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators. Br J Cancer  2000; 83: 707 -14. Google Scholar 39 Buccheri G, Ferrigno D. Vinorelbine in elderly patients with inoperable nonsmall cell lung carcinoma: a phase II study. Cancer  2000; 88: 2677 -85. Google Scholar 40 Giaccone G, Splinter TA, Debruyne C, Kho GS, Lianes P, van Zandwijk N, et al. Randomized study of paclitaxel-cisplatin versus cisplatinteniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol  1998 ; 16: 2133 -41. Google Scholar 41 Socinski MA, Steagall A, Gillenwater H. Second-line chemotherapy with 96-hour infusional paclitaxel in refractory non-small cell lung cancer: report of a phase II trial. Cancer Invest  1999 ; 17: 181 -8. Google Scholar 42 Hickish TF, Smith IE, Nicolson MC, Ashley S, Priest K, Spencer L, et al. A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer. Br J Cancer  1998 ; 77: 1966 -70. Google Scholar 43 Helsing M, Bergman B, Thaning L, Hero U. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Eur J Cancer  1998 ; 34: 1036 -44. Google Scholar 44 Geddes DM, Dones L, Hill E, Law K, Harper PG, Spiro SG, et al. Quality of life during chemotherapy for small cell lung cancer: assessment and use of a daily diary card in a randomized trial. Eur J Cancer  1990 ; 26: 484 -92. Google Scholar 45 Feld R, Pater J, Goodwin PJ, Grossman R, Coy P, Murray N. The restaging of responding patients with limited small cell lung cancer. Is it really useful. Chest  1993 ; 103: 1010 -6. Google Scholar 46 Colice GL, Birkmeyer JD, Black WC, Littenberg B, Silvestri G. Cost-effectiveness of head CT in patients with lung cancer without clinical evidence of metastases. Chest  1995 ; 108: 1264 -71. Google Scholar 47 Chouaid C, Bassinet L, Fuhrman C, Monnet I, Housset B. Routine use of granulocyte colony-stimulating factor is not cost-effective and does not increase patient comfort in the treatment of small-cell lung cancer: an analysis using a Markov model. J Clin Oncol  1998 ; 16: 2700 -7. Google Scholar 48 Virgo KS, Naunheim KS, McKirgan LW, Kissling ME, Lin JC, Johnson FE. Cost of patient follow-up after potentially curative lung cancer treatment. J Thorac Cardiovasc Surg  1996 ; 112: 356 -63. Google Scholar 49 Hohenberg G, Sedlmayer F. Costs of standard and conformal photon radiotherapy in Austria. Strahlenther Onkol  1999 ; 175 Suppl 2: 99 -101. Google Scholar 50 Kennedy W, Reinharz D, Tessier G, Contandriopoulos AP, Trabut I, Champagne F, et al. Cost utility of chemotherapy and best supportive care in non-small cell lung cancer. Pharmacoeconomics  1995 ; 8: 316 -23. Google Scholar 51 Nichols CR, Fox EP, Roth BJ, Williams SD, Loehrer PJ, Einhorn LH. Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor. J Clin Oncol  1994; 12: 1245 -50. Google Scholar 52 Kosuda S, Ichihara K, Watanabe M, Kobayashi H, Kusano S. Decision-tree sensitivity analysis for cost-effectiveness of chest 2-fluoro-2-D-[(18)F]fluorodeoxyglucose positron emission tomography in patients with pulmonary nodules (non-small cell lung carcinoma) in Japan. Chest  2000; 117: 346 -53. Google Scholar 53 Raab SS, Hornberger J. The effect of a patient's risk-taking attitude on the cost effectiveness of testing strategies in the evaluation of pulmonary lesions. Chest  1997 ; 111: 1583 -90. Google Scholar 54 Chancellor JV, Coyle D, Drummond MF. Constructing health state preference values from descriptive quality of life outcomes: mission impossible. Qual Life Res  1997 ; 6: 159 -68. Google Scholar 55 Coyle D, Drummond MF. Costs of conventional radical radiotherapy versus continuous hyperfractionated accelerated radiotherapy (CHART) in the treatment of patients with head and neck cancer or carcinoma of the bronchus. Clin Oncol  1997; 9: 313 -21. Google Scholar 56 Tennvall GR, Fernberg JO. Economic evaluation of gemcitabine single agent therapy compared with standard treatment in stage IIIB and IV non-small cell lung cancer. Med Oncol  1998 ; 15: 129 -36. Google Scholar 57 Kennedy CA, Gray AM, Denman AR, Phillips PS. A cost-effectiveness analysis of a residential radon remediation programme in the United Kingdom. Br J Cancer  1999; 81: 1243 -7. Google Scholar 58 Remer EM, Obuchowski N, Ellis JD, Rice TW, Adelstein DJ, Baker ME. Adrenal mass evaluation in patients with lung carcinoma: a cost-effectiveness analysis. AJR Am J Roentgenol  2000 ; 174: 1033 -9. Google Scholar 59 Copley-Merriman C, Martin C, Johnson N, Sacristan JA, Drings PA, Bosanquet N. Economic value of gemcitabine in non-small cell lung cancer. Semin Oncol  1996; 23: 90 -8. Google Scholar 60 Copley-Merriman C, Corral J, King K, Whiteside R, Voi M, Dorr FA, et al. Economic value of gemcitabine compared to cisplatin and etoposide in non-small cell lung cancer. Lung Cancer  1996 ; 14: 45 -61. Google Scholar 61 Evans WK, Will BP, Berthelot JM, Wolfson MC. The cost of managing lung cancer in Canada. Oncology  1995 ; 9: 147 -53. Google Scholar 62 Chella A, Ambrogi MC, Ribechini A, Mussi A, Fabrini MG, Silvano G, et al. Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Lung Cancer  2000; 27: 169 -75. Google Scholar 63 Lewis RJ, Caccavale RJ, Bocage JP, Widmann MD. Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy: a more patient-friendly oncologic resection. Chest  1999 ; 116: 1119 -24. Google Scholar 64 Herskovic A, Fisher J, Orton B, Lee CK, Chang JH, Sandhu T, et al. Accelerated hyperfractionation in patients with non-small cell bronchogenic cancers as a cost-effective and user- and patient-friendly schedule. Cancer Invest  2000; 18: 537 -43. Google Scholar 65 Jaakkimainen L, Goodwin PJ, Pater J. Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in non-small cell lung cancer. J Clin Oncol  1990 ; 8: 1301 -9. Google Scholar 66 Dajczman E, Fu LY, Small D, Wolkove N, Kreisman H. Treatment of small cell lung carcinoma in the elderly. Cancer  1996 ; 77: 2032 -8. Google Scholar 67 Smith TJ, Penberthy LT, Desch CE, Whittemore M, Newschaffer CJ, Hillner BE, et al. Differences in initial treatment patterns and outcomes of lung cancer in the elderly. Lung Cancer  1995 ; 13: 235 -52. Google Scholar 68 Rose JH, O'Toole EE, Dawson NV, Thomas C, Connors AFJ, Wenger NS, et al. Age differences in care practices and outcomes for hospitalized patients with cancer. J Am Geriatr Soc  2000 ; 48(5 Suppl): S25 -32. Google Scholar 69 Bach PB, Cramer LD, Warren JL, Begg CB. Racial differences in the treatment of early-stage lung cancer. N Engl J Med  1999 ; 341: 1198 -205. Google Scholar 70 McLean AN, Semple PA, Franklin DH, Petrie G, Millar EA, Douglas JG. The Scottish multi-centre prospective study of bronchoscopy for bronchial carcinoma and suggested audit standards. Respir Med  1998 ; 92: 1110 -5. Google Scholar 71 Fergusson RJ, Gregor A, Dodds R, Kerr G. Management of lung cancer in south east Scotland. Thorax  1996 ; 51: 569 -74. Google Scholar 72 Earle CC, Venditti LN, Neumann PJ, Gelber RD, Weinstein MC, Potosky AL, et al. Who gets chemotherapy for metastatic lung cancer. Chest  2000; 117: 1239 -46. Google Scholar 73 Choy H, Shyr Y, Cmelak AJ, Mohr PJ, Johnson DH. Patterns of practice survey for nonsmall cell lung carcinoma in the U.S. Cancer  2000; 88: 1336 -46. Google Scholar 74 Taenzer P, Bultz BD, Carlson LE, Speca M, DeGagne T, Olson K, et al. Impact of computerized quality of life screening on physician behaviour and patient satisfaction in lung cancer outpatients. Psychooncology  2000; 9: 203 -13. Google Scholar 75 Davidson JR, Brundage MD, Feldman-Stewart D. Lung cancer treatment decisions: patients' desires for participation and information. Psychooncology  1999; 8: 511 -20. Google Scholar 76 Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst  1993 ; 85: 365 -76. Google Scholar 77 Osoba D, Zee B, Pater J, Warr D, Kaizer L, Latreille J. Psychometric properties and responsiveness of the EORTC Quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer. Qual Life Res  1994; 3: 353 -64. Google Scholar 78 Osoba D, Murray N, Gelmon K, Karsai H, Knowling M, Shah A, et al. Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy. Oncology (Huntingt)  1994 ; 8: 61 -5. Google Scholar 79 Zieren HU, Muller JM, Hamberger U, Pichlmaier H. Quality of life after surgical therapy of bronchogenic carcinoma. Eur J Cardiothorac Surg  1996; 10: 233 -7. Google Scholar 80 Spilker B. Quality of life and pharmacoeconomics in clinical trials . 2nd ed. Philadelphia (PA): Lippincott-Raven; 1996 . Google Scholar 81 Hopwood P, Harvey A, Davies J, Stephens RJ, Girling DJ, Gibson D, et al. Survey of the administration of quality of life (QL) questionnaires in three multicentre randomised trials in cancer. The Medical Research Council Lung Cancer Working Party the CHART Steering Committee. Eur J Cancer  1998; 34: 49 -57. Google Scholar 82 Hendriks J, Van Schil P, van Meerbeeck J, Gdeedo A, Van Marck E, Vanmaele R, et al. Short-term survival after major pulmonary resections for bronchogenic carcinoma. Acta Chir Belg  1996 ; 96: 273 -9. Google Scholar 83 Lutz ST, Huang DT, Ferguson CL, Kavanagh BD, Tercilla OF, Lu J. A retrospective quality of life analysis using the Lung Cancer Symptom Scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys  1997 ; 37: 117 -22. Google Scholar 84 Joss RA, Alberto P, Hurny C, Bacchi M, Leyvraz S, Thurlimann B, et al. Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer. A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK). Ann Oncol  1995 ; 6: 41 -8. Google Scholar 85 Montazeri A, Milroy R, Hole D, McEwen J, Gillis CR. Anxiety and depression in patients with lung cancer before and after diagnosis: findings from a population in Glasgow, Scotland. J Epidemiol Community Health  1998; 52: 203 -4. Google Scholar 86 Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, et al. Mitomycin, ifosphamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life [see comments]. J Clin Oncol  1999 ; 17: 3188 -94. Google Scholar 87 EORTC Quality of Life. Quality of life questionnaire. QLQ-C30. Available from: http://www.eortc.be/home/qol [Last accessed: 09/25/2001.]. Google Scholar 88 Bergman B, Aaronson NK, Ahmedzai S, Kaasa S, Sullivan M. The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer  1994 ; 30A: 635 -42. Google Scholar 89 Bergman B, Sullivan M, Sorenson S. Quality of life during chemotherapy for small cell lung cancer. II. A longitudinal study of the EORTC Core Quality of Life Questionnaire and comparison with the Sickness Impact Profile. Acta Oncol  1992 ; 31: 19 -28. Google Scholar 90 Herndon JE, Fleishman S, Kosty MP, Green MR. A longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931 [see comments]. Control Clin Trials  1997 ; 18: 286 -300. Google Scholar 91 Kosmidis P. Quality of life as a new end point. Chest  1996; 109: 110S -112S. Google Scholar 92 Cella DF, Tulsky DS, Gray GSB, Linn E, Bonomi A, Silberman M, et al. The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol  1993 ; 11: 570 -9. Google Scholar 93 FACIT Functional Assessment of Chronic Illness Therapy. Available from: http://www.facit.org [Last accessed: 09/25/2001.]. Google Scholar 94 Cella DF, Bonomi AE, Lloyd SR, Tulsky DS, Kaplan E, Bonomi P. Reliability and validity of the Functional Assessment of Cancer Therapy-Lung (FACT-L) quality of life instrument. Lung Cancer  1995 ; 12: 199 -220. Google Scholar 95 Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol  2000 ; 18: 623 -31. Google Scholar 96 Hollen PJ, Gralla RJ, Kris MG, Potanovich LM. Quality of life assessment in individuals with lung cancer: testing the Lung Cancer Symptom Scale (LCSS). Eur J Cancer  1993 ; 29A(Suppl 1): S51 -8. Google Scholar 97 Hollen PJ, Gralla RJ, Kris MG, Cox C. Quality of life during clinical trials: conceptual model for the Lung Cancer Symptom Scale (LCSS). Support Care Cancer  1994; 2: 213 -22. Google Scholar 98 Hollen PJ, Gralla RJ, Kris MG, Cox C, Belani CP, Grunberg SM, et al. Measurement of quality of life in patients with lung cancer in multicenter trials of new therapies. Psychometric assessment of the Lung Cancer Symptom Scale. Cancer  1994; 73: 2087 -98. Google Scholar 99 Hollen PJ, Gralla RJ, Kris MG, Eberly SW, Cox C. Normative data and trends in quality of life from the Lung Cancer Symptom Scale (LCSS). Support Care Cancer  1999; 7: 140 -8. Google Scholar 100 Hollen PJ, Gralla RJ, Liepa AM, Rusthoven JJ. Validation of a quality of life instrument for patients with pleural mesothelioma: Lung Cancer Symptom Scale [abstract 1579]. Proc Am Soc Clin Oncol  2001 ; 20: Google Scholar 101 Lung Cancer Symptoms Scale (LCSS). Available from: http://www.lcssql.com [Last accessed: 09/25/02.]. Google Scholar 102 MAPI Research Institute. QOLID: Quality of life instrument database. Available from: http://www.qlmed.org/LCSS [Last accessed: 09/25/2001.]. Google Scholar 103 Gelber RD, Goldhirsch A, Cole BF, Wieand HS, Schroeder G, Krook JE. A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer. J Natl Cancer Inst  1996; 88: 1039 -45. Google Scholar 104 Goldhirsch A, Gelber RD, Simes RJ, Glasziou P, Coates AS. Costs and benefits of adjuvant therapy in breast cancer: A quality-adjusted survival analysis. J Clin Oncol  1989 ; 7: 36 -44. Google Scholar 105 Patrick DL, Starks KC, Cain RF, Uhlmann RF, Pearlman RA. Measuring preferences for health states worse than death. Med Decis Making  1994; 14: 9 -18. Google Scholar 106 Bailey AJ, Parmar MK, Stephens RJ. Patient-reported short-term and long-term physical and psychologic symptoms: results of the continuous hyperfractionated accelerated [correction of acclerated] radiotherapy (CHART) randomized trial in non-small-cell lung cancer. CHART Steering Committee. J Clin Oncol  1998; 16: 3082 -93. Google Scholar 107 Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol  1998; 16: 139 -44. Google Scholar 108 Souhami RL, Spiro SG, Rudd RM, Ruiz de Elvira MC, James LE, Gower NH, et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy [see comments]. J Natl Cancer Inst  1997; 89: 577 -80. Google Scholar 109 Rowland KMJ, Loprinzi CL, Shaw EG, Maksymiuk AW, Kuross SA, Jung SH, et al. Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study. J Clin Oncol  1996; 14: 135 -41. Google Scholar 110 Loprinzi CL, Goldberg RM, Su JQ, Mailliard JA, Kuross SA, Maksymiuk AW, et al. Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol  1994 ; 12: 1126 -9. Google Scholar 111 Herndon JE, Fleishman S, Kornblith AB, Kosty M, Green MR, Holland J. Is quality of life predictive of the survival of patients with advanced nonsmall cell lung carcinoma. Cancer  1999 ; 85: 333 -40. Google Scholar 112 Nakada S, Nagao K, Takiguchi Y, Tatsumi K, Kuriyama T. Quality of life and anxiety before and after lung cancer chemotherapy: relationship to patient's personality. Intern Med  1996 ; 35: 611 -6. Google Scholar 113 Shevlin PM, Muers MF, Peake MD, Hosker HS, Stead ML, Poulter KM, et al. Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosphamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer. Lung Cancer  1998 ; 21: 115 -26. Google Scholar 114 Kosmidis P, Mylonakis N, Fountzilas G, Samantas E, Athanassiadis A, Pavlidis N, et al. Paclitaxel (175 mg/m2) plus carboplatin versus paclitaxel (225 mg/m2) plus carboplatin in non-small cell lung cancer: a randomized study. Semin Oncol  1997 ; 24: S12 -30-33. Google Scholar 115 Ranson MR, Jayson G, Perkins S, Anderson H, Thatcher N. Single-agent paclitaxel in advanced non-small cell lung cancer: single-center phase II study using a 3-hour administration schedule. Semin Oncol  1997; 24: S12 -6-9. Google Scholar 116 Gower NH, Rudd RM, Ruiz de Elvira MC, Spiro SG, James LE, Harper PG, et al. Assessment of `quality of life' using a daily diary card in a randomised trial of chemotherapy in small-cell lung cancer. Ann Oncol  1995; 6: 575 -80. Google Scholar 117 Klemm PR. Variables influencing psychosocial adjustment in lung cancer: a preliminary study. Oncol Nurs Forum  1994 ; 21: 1059 -62. Google Scholar 118 Pujol JL, Monnier A, Berille J, Cerrina ML, Douillard JY, Riviere A, et al. Phase II study of nitrosourea fotemustine as single-drug chemotherapy in poor-prognosis non-small-cell lung cancer. Br J Cancer  1994; 69: 1136 -40. Google Scholar 119 Montazeri A, Milroy R, Gillis CR, McEwen J. Quality of life: perception of lung cancer patients. Eur J Cancer  1996 ; 32A: 2284 -9. Google Scholar 120 Highfield MF. Spiritual health of oncology patients. Nurse and patient perspectives. Cancer Nurs  1992 ; 15: 1 -8. Google Scholar 121 Fayers PM, Bleehen NM, Girling DJ, Stephens RJ. Assessment of quality of life in small-cell lung cancer using a Daily Diary Card developed by the Medical Research Council Lung Cancer Working Party. Br J Cancer  1991; 64: 299 -306. Google Scholar 122 Maasilta PK, Rautonen JK, Mattson MT, Mattson KV. Quality of life assessment during chemotherapy for non-small cell lung cancer. Eur J Cancer  1990; 26: 706 -8. Google Scholar 123 Kurtz ME, Kurtz JC, Stommel M, Given CW, Given B. Loss of physical functioning among geriatric cancer patients: relationships to cancer site, treatment, comorbidity and age. Eur J Cancer  1997 ; 33: 2352 -8. Google Scholar 124 Berckman KL, Austin JK. Causal attribution, perceived control, and adjustment in patients with lung cancer. Oncol Nurs Forum  1993 ; 20: 23 -30. Google Scholar 125 Macbeth FR, Bolger JJ, Hopwood P, Bleehen NM, Cartmell J, Girling DJ, et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party. Clin Oncol (R Coll Radiol)  1996 ; 8: 167 -75. Google Scholar 126 Dales RE, Belanger R, Shamji FM, Leech J, Crepeau A, Sachs HJ. Quality-of-life following thoracotomy for lung cancer. J Clin Epidemiol  1994; 47: 1443 -9. Google Scholar 127 Ahles TA, Silberfarb PM, Rundle AC, Holland JC, Kornblith AB, Canellos GP, et al. Quality of life in patients with limited small-cell carcinoma of the lung receiving chemotherapy with or without radiation therapy, for cancer and leukemia group B. Psychother Psychosom  1994 ; 62: 193 -9. Google Scholar 128 Glimelius B, Birgegard G, Hoffman K, Hagnebo C, Hogman G, Kvale G, et al. Improved care of patients with small cell lung cancer. Nutritional and quality of life aspects. Acta Oncol  1992 ; 31: 823 -31. Google Scholar 129 Thongprasert S. Lung cancer and quality of life. Aust N Z J Med  1998; 28: 397 -9. Google Scholar 130 Osoba D. Self-rating symptom checklists: a simple method for recording and evaluating symptom control in oncology. Cancer Treat Rev  1993; 19(Suppl A): 43 -51. Google Scholar 131 Clipp EC, George LK. Patients with cancer and their spouse caregivers. Perceptions of the illness experience. Cancer  1992 ; 69: 1074 -9. Google Scholar 132 Eguchi K, Fukutani M, Kanazawa M, Tajima K, Tanaka Y, Morioka C, et al. Feasibility study on quality-of-life questionnaires for patients with advanced lung cancer. Jpn J Clin Oncol  1992 ; 22: 185 -93. Google Scholar 133 Ishihara Y, Sakai H, Nukariya N, Kobayashi K, Yoneda S, Matsuoka R, et al. A diary form quality of life questionnaire for Japanese patients with lung cancer and summarization techniques for longitudinal assessment. Respirology  1999; 4: 53 -61. Google Scholar 134 Thongprasert S, Sanquanmitr P. Usefulness of the Thai modified functional living index—cancer (T-FLIC) and the Thai modified quality of life index (T-QLI) for advanced non-small cell lung cancer. Gan To Kagaku Ryoho  1995; 22 (Suppl 3): 226 -9. Google Scholar 135 De Valck C, Vinck J. Health locus of control and quality of life in lung cancer patients. Patient Educ Couns  1996 ; 28: 179 -86. Google Scholar 136 Montazeri A, Milroy R, Gillis CR, McEwen J. Interviewing cancer patients in a research setting: the role of effective communication. Support. Care Cancer  1996; 4: 447 -54. Google Scholar 137 Schag CA, Ganz PA, Wing DS, Sim MS, Lee JJ. Quality of life in adult survivors of lung, colon and prostate cancer. Qual Life Res  1994; 3: 127 -41. Google Scholar 138 Hurny C, Bernhard J, Joss R, Schatzmann E, Cavalli F, Brunner K, et al. “Fatigue and malaise” as a quality-of-life indicator in small-cell lung cancer patients. The Swiss Group for Clinical Cancer Research (SAKK). Support Care Cancer  1993 ; 1: 316 -20. Google Scholar 139 Papatheofanis FJ. Utility evaluations for Markov states of lung cancer for PET-based disease management. Q J Nucl Med  2000 : 44: 186 -90. Google Scholar 140 Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, et al. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer  2000 ; 27: 145 -57. Google Scholar 141 ten Bokkel H, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen PL, et al. Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer. Lung Cancer  1999 ; 26: 85 -94. Google Scholar 142 Tishelman C, Degner LF, Mueller B. Measuring symptom distress in patients with lung cancer. A pilot study of experienced intensity and importance of symptoms Cancer Nurs  2000 ; 23: 82 -90. Google Scholar [published erratum appears in Cancer Nurs  2000 ; 23: 163 ]. Google Scholar 143 Faller H, Bulzebruck H, Drings P, Lang H. Coping, distress, and survival among patients with lung cancer. Arch Gen Psychiatry  1999 ; 56: 756 -62. Google Scholar 144 Langendijk JA, ten Velde GP, Aaronson NK, de Jong JM, Muller MJ, Wouters EF. Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study. Int J Radiat Oncol Biol Phys  2000 ; 47: 149 -55. Google Scholar 145 Schaafsma J, Coy P. Response of global quality of life to high-dose palliative radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys  2000; 47: 691 -701. Google Scholar 146 Quantin X, Riviere A, Daures JP, Oliver P, Comte-Bardonnet M, Khial F, et al. Phase I-II study of high dose epirubicin plus cisplatin in unresectable non-small-cell lung cancer: searching for the maximal tolerated dose. Am J Clin Oncol  2000 ; 23: 192 -6. Google Scholar 147 Anderson H, Hopwood P, Stephens RJ, Thatcher N, Cottier B, Nicholson M, et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer—a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer  2000 ; 83: 447 -53. Google Scholar 148 Kosmas C, Tsavaris NB, Polyzos A, Kalofonos HP, Sepsas E, Malamos NA, et al. A phase II study of paclitaxel-ifosphamide-cisplatin combination in advanced nonsmall cell lung carcinoma. Cancer  2000 ; 89: 774 -82. Google Scholar 149 Hyodo I, Eguchi K, Takigawa N, Segawa Y, Hosokawa Y, Kamejima K, et al. Psychological impact of informed consent in hospitalized cancer patients. A sequential study of anxiety and depression using the hospital anxiety and depression scale. Support Care Cancer  1999 ; 7: 396 -9. Google Scholar 150 Kurtz ME, Kurtz JC, Stommel M, Given CW, Given BA. Symptomatology and loss of physical functioning among geriatric patients with lung cancer. J Pain Symptom Manage  2000 ; 19: 249 -56. Google Scholar 151 Movsas B, Scott C, Sause W, Byhardt R, Komaki R, Cox J, et al. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies. Int J Radiat Oncol Biol Phys  1999 ; 45: 1143 -9. Google Scholar 152 Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, et al. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  2000; 92: 1074 -80. Google Scholar 153 Agteresch HJ, Dagnelie PC, van der Gaast A, Stijnen T, Wilson JH. Randomized clinical trial of adenosine 5′-triphosphate in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst  2000 ; 92: 321 -8. Google Scholar 154 Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol  2000 ; 18: 2095 -103. Google Scholar 155 Hopwood P, Stephens RJ. Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data. J Clin Oncol  2000; 18: 893 -903. Google Scholar 156 Thatcher N, Girling DJ, Hopwood P, Sambrook RJ, Qian W, Stephens RJ. Improving survival without reducing quality of life in small-cell lung cancer patients by increasing the dose-intensity of chemotherapy with granulocyte colony-stimulating factor support: results of a British Medical Research Council Multicenter Randomized Trial. Medical Research Council Lung Cancer Working Party. J Clin Oncol  2000 ; 8: 395 -404. Google Scholar 157 Crino L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, et al. Gemcitabine and cisplatin versus mitomycin, ifosphamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol  1999 ; 17: 3522 -30. Google Scholar 158 Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol  1999 ; 17: 12 -8. Google Scholar 159 Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol  2000 ; 18: 2529 -36. Google Scholar 160 Sugiura H, Morikawa T, Kaji M, Sasamura Y, Kondo S, Katoh H. Long-term benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer. Surg Laparosc Endosc Percutan Tech  1999; 9: 403 -8. Google Scholar 161 Goldberg-Kahn B, Healy JC, Bishop JW. The cost of diagnosis: a comparison of four different strategies in the workup of solitary radiographic lung lesions. Chest  1997 ; 111: 870 -6. Google Scholar 162 Gambhir SS, Hoh CK, Phelps ME, Madar I, Maddahi J. Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med  1996 ; 37: 1428 -36. Google Scholar 163 Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg  1998; 66: 1876 -83. Google Scholar 164 Gambhir SS, Shepherd JE, Shah BD, Hart E, Hoh CK, Valk PE, et al. Analytical decision model for the cost-effective management of solitary pulmonary nodules. J Clin Oncol  1998 ; 16: 2113 -25. Google Scholar 165 Hazelrigg SR, Nunchuck SK, Landreneau RJ, Mack MJ, Naunheim KS, Seifert PE, et al. Cost analysis for thoracoscopy: thoracoscopic wedge resection. Ann Thorac Surg  1993 ; 56: 633 -5. Google Scholar 166 Raab SS, Slagel DD, Hughes JH, Thomas PA, Silverman JF. Sensitivity and cost-effectiveness of fine-needle aspiration with immunocytochemistry in the evaluation of patients with a pulmonary malignancy and a history of cancer. Arch Pathol Lab Med  1997 ; 121: 695 -700. Google Scholar 167 Anonymous. Investigation for mediastinal disease in patients with apparently operable lung cancer. Canadian Lung Oncology Group. Ann Thorac Surg  1995; 60: 1382 -9. Google Scholar 168 Govert JA, Kopita JM, Matchar D, Kussin PS, Samuelson WM. Cost-effectiveness of collecting routine cytologic specimens during fiberoptic bronchoscopy for endoscopically visible lung tumor. Chest  1996 ; 109: 451 -6. Google Scholar 169 Richardson GE, Venzon DJ, Edison M, Brown M, Frame JN, Ihde DC, et al. Application of an algorithm for staging small-cell lung cancer can save one third of the initial evaluation costs. Arch Intern Med  1993 ; 153: 329 -37. Google Scholar 170 Gould MK, Lillington GA. Strategy and cost in investigating solitary pulmonary nodules. Thorax  1998 ; 53(Suppl 2): S32 -7. Google Scholar 171 Ford ES, Kelly AE, Teutsch SM, Thacker SB, Garbe PL. Radon and lung cancer: a cost-effectiveness analysis. Am J Public Health  1999 ; 89: 351 -7. Google Scholar 172 Wolstenholme JL, Whynes DK. The hospital costs of treating lung cancer in the United Kingdom. Br J Cancer  1999 ; 80: 215 -8. Google Scholar 173 Coy P, Schaafsma J, Schofield JA, Nield JA. Comparative costs of lung cancer management. Clin Invest Med  1994 ; 17: 577 -87. Google Scholar 174 Glaspy JA, Bleecker G, Crawford J, Stoller R, Strauss M. The impact of therapy with filgrastim (recombinant granulocyte colony-stimulating factor) on the health care costs associated with cancer chemotherapy. Eur J Cancer  1993; 29A(Suppl 7): S23 -30. Google Scholar 175 Baker MS, Kessler LG, Urban N, Smucker RC. Estimating the treatment costs of breast and lung cancer. Med Care  1991 ; 29: 40 -9. Google Scholar 176 Hillner BE, Smith TJ. Cost-effectiveness analysis of three regimens using vinorelbine (Navelbine) for non-small cell lung cancer. Semin Oncol  1996; 23: 25 -30. Google Scholar 177 Bergman B, Sorenson S. Hospitalization during chemotherapy for small cell lung cancer. Acta Oncol  1990 ; 29: 977 -82. Google Scholar 178 Koch P, Johnson N, van Schaik J, Andersen S, Blatter J, Bosanquet N, et al. Gemcitabine: clinical and economic impact in inoperable non-small cell lung cancer. Anticancer Drugs  1995 ; 6(Suppl 6): 49 -54. Google Scholar 179 Doyle JJ, Dezii CM, Sadana A. A pharmacoeconomic evaluation of cisplatin in combination with either etoposide or etoposide phosphate in small cell lung cancer. Semin Oncol  1996 ; 23: 51 -60. Google Scholar 180 Evans WK, Will BP, Berthelot JM, Earle CC. Cost of combined modality interventions for stage III non-small-cell lung cancer. J Clin Oncol  1997; 15: 3038 -48. Google Scholar 181 Earle CC, Evans WK. A comparison of the costs of paclitaxel and best supportive care in stage IV non-small-cell lung cancer. Cancer Prev Control  1997; 1: 282 -8. Google Scholar 182 Earle CC, Evans WK. Cost-effectivenes of paclitaxel plus cisplatin in advanced non-small-cell lung cancer. Br J Cancer  1999 ; 80: 815 -20. Google Scholar 183 Evans WK, Will BP, Berthelot JM, Wolfson MC. Diagnostic and therapeutic approaches to lung cancer in Canada and their costs. Br J Cancer  1995; 72: 1270 -7. Google Scholar 184 Evans WK, Will BP, Berthelot JM, Wolfson MC. The cost of managing lung cancer in Canada. Oncology (Huntingt)  1995 ; 9: 147 -53. Google Scholar 185 Evans WK, Will BP, Berthelot JM, Wolfson MC. Estimating the cost of lung cancer diagnosis and treatment in Canada: the POHEM model. Can J Oncol  1995; 5: 408 -19. Google Scholar 186 Evans WK, Will BP, Berthelot JM, Wolfson MC. The economics of lung cancer management in Canada. Lung Cancer  1996 ; 14: 19 -29. Google Scholar 187 Evans WK, Burpee C, Skinn B, Stewart DJ, Stapleton J, Armstrong J, et al. An evaluation of the costs of outpatient chemotherapy administration for small cell lung cancer. Can J Oncol  1993 ; 3: 225 -32. Google Scholar 188 Evans WK, Le Chevalier T. The cost-effectiveness of navelbine alone or in combination with cisplatin in comparison to other chemotherapy regimens and best supportive care in stage IV non-small cell lung cancer. Eur J Cancer  1996; 32A: 2249 -55. Google Scholar 189 Evans WK. An estimate of the cost effectiveness of gemcitabine in stage IV non-small cell lung cancer. Semin Oncol  1996 ; 23: 82 -9. Google Scholar 190 Hillner BE, McDonald MK, Desch CE, Smith TJ, Penberthy LT, Maddox P, et al. Costs of care associated with non-small-cell lung cancer in a commercially insured cohort. J Clin Oncol  1998 ; 16: 1420 -4. Google Scholar 191 Jaakkimainen L, Goodwin PJ, Pater J, Warde P, Murray N, Rapp E. Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer. J Clin Oncol  1990 ; 8: 1301 -9. Google Scholar 192 Palmer AJ, Brandt A. The cost-effectiveness of four cisplatin-containing chemotherapy regimens in the treatment of stages III B and IV non-small cell lung cancer: an Italian perspective. Monaldi Arch Chest Dis  1996; 51: 279 -88. Google Scholar 193 Rosenthal MA, Webster PJ, Gebski VJ, Stuart-Harris RC, Langlands AO, Boyages J. The cost of treating small cell lung cancer. Med J Aust  1992; 156: 605 -10. Google Scholar 194 Smith TJ, Hillner BE, Neighbors DM, McSorley PA, Le Chevalier T. Economic evaluation of a randomized clinical trial comparing vinorelbine, vinorelbine plus cisplatin, and vindesine plus cisplatin for non-small-cell lung cancer. J Clin Oncol  1995 ; 13: 2166 -73. Google Scholar 195 Vergnenegre A, Perol M, Pham E. Cost analysis of hospital treatment—two chemotherapic regimens for non-surgical non-small cell lung cancer. GFPC (Groupe Francais Pneumo Cancerologie). Lung Cancer  1996; 14: 31 -44. Google Scholar 196 Messori A, Trippoli S, Tendi E. G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation. J Clin Pharm Ther  1996 ; 21: 57 -63. Google Scholar 197 Pashko S, Johnson DH. Potential cost savings of oral versus intravenous etoposide in the treatment of small cell lung cancer. Pharmacoeconomics  1992; 1: 293 -7. Google Scholar 198 Williamson SK, Crowley JJ, Livingston RB, Panella TJ, Goodwin JW. Phase II trial and cost analysis of fazarabine in advanced non-small cell carcinoma of the lung: a Southwest Oncology Group study. Invest New Drugs  1995; 13: 67 -71. Google Scholar 199 Polednak AP, Shevchenko IP. Hospital charges for terminal care of cancer patients dying before age 65. J Health Care Finance  1998 ; 25: 26 -34. Google Scholar 200 Sugi K, Kaneda Y, Nawata K, Fujita N, Ueda K, Nawata S, et al. Cost analysis for thoracoscopy: thoracoscopic wedge resection and lobectomy. Surg Today  1998; 28: 41 -5. Google Scholar 201 Papatheofanis FJ. The willingness to pay for positron emission tomography (PET): evaluation of suspected lung cancer using contingent valuation. Q J Nucl Med  2000 ; 44: 191 -6. Google Scholar 202 Evans WK, Dahrouge S, Stapleton J, Quinn C, Pollock D, Waterfield B, et al. An estimate of the cost of conducting phase II trials in lung cancer. Lung Cancer  2000 ; 28: 85 -95. Google Scholar 203 Sacristan JA, Kennedy-Martin T, Rosell R, Cardenal F, Anton A, Lomas M, et al. Economic evaluation in a randomized phase III clinical trial comparing gemcitabine/cisplatin and etoposide/cisplatin in non-small cell lung cancer. Lung Cancer  2000 ; 28: 97 -107. Google Scholar 204 Annemans L, Giaccone G, Vergnenegre A. The cost-effectiveness of paclitaxel (Taxol) + cisplatin is similar to that of teniposide + cisplatin in advanced non-small cell lung cancer: a multicountry analysis. Anticancer Drugs  1999; 10: 605 -15. Google Scholar 205 Gilbert S, Reid KR, Lam MY, Petsikas D. Who should follow up lung cancer patients after operation. Ann Thorac Surg  2000 ; 69: 1696 -700. Google Scholar 206 Brunelli A, Al Refai M, Muti M, Sabbatini A, Fianchini A. Pleural tent after upper lobectomy: a prospective randomized study. Ann Thorac Surg  2000; 69: 1722 -4. Google Scholar 207 Tanaka K, Kubota K, Kodama T, Nagai K, Nishiwaki Y. Extrathoracic staging is not necessary for non-small-cell lung cancer with clinical stage T1-2 N0. Ann Thorac Surg . 1999 ; 68: 1039 -42. Google Scholar 208 Laroche C, Fairbairn I, Moss H, Pepke-Zaba J, Sharples L, Flower C, et al. Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer. Thorax  2000; 55: 359 -63. Google Scholar 209 Aabakken L, Silvestri GA, Hawes R, Reed CE, Marsi V, Hoffman B. Cost-efficacy of endoscopic ultrasonography with fine-needle aspiration vs. mediastinotomy in patients with lung cancer and suspected mediastinal adenopathy. Endoscopy  1999 ; 31: 707 -11. Google Scholar 210 Berthelot JM, Will BP, Evans WK, Coyle D, Earle CC, Bordeleau L. Decision framework for chemotherapeutic interventions for metastatic non-small-cell lung cancer. J Natl Cancer Inst  2000 ; 92: 1321 -9. Google Scholar 211 Crocket JA, Wong EY, Lien DC, Nguyen KG, Chaput MR, McNamee C. Cost effectiveness of transbronchial needle aspiration. Can Respir J  1999 ; 6: 332 -5. Google Scholar 212 Kesson E, Bucknall CE, McAlpine LG, Milroy R, Hole D, Vernon DR, et al. Lung cancer—management and outcome in Glasgow, 1991-92. Br J Cancer  1998; 78: 1391 -5. Google Scholar 213 Walsh GL, Winn RJ. Baseline institutional compliance with NCCN guidelines: non-small-cell lung cancer. Oncology (Huntingt)  1997 ; 11: 161 -70. Google Scholar 214 Richardson GE, Thursfield VJ, Giles GG. Reported management of lung cancer in Victoria in 1993: comparison with best practice. Anti-Cancer Council of Victoria Lung Cancer Study Group. Med J Aust  2000 ; 172: 321 -4. Google Scholar 215 Silvestri G, Pritchard R, Welch HG. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews. BMJ  1998 ; 317: 771 -5. Google Scholar 216 Brundage MD, Davidson JR, Mackillop WJ. Trading treatment toxicity for survival in locally advanced non-small cell lung cancer. J Clin Oncol  1997; 15: 330 -40. Google Scholar 217 Brundage MD, Davidson JR, Mackillop WJ, Feldman-Stewart D, Groome P. Using a treatment-tradeoff method to elicit preferences for the treatment of locally advanced non-small-cell lung cancer. Med Decis Making  1998; 18: 256 -67. Google Scholar 218 Brundage MD, Groome PA, Feldman-Stewart D, Davidson JR, Mackillop WJ. Decision analysis in locally advanced non-small-cell lung cancer: is it useful? J Clin Oncol  1997 ; 15: 873 -83. Google Scholar 219 Erkurt E, Tunali C, Erkisi M. Primary therapeutic decision-making in inoperable non-small cell lung cancer. Int J Radiat Oncol Biol Phys  2000; 46: 439 -44. Google Scholar 220 Tamburini M, Buccheri G, Brunelli C, Ferrigno D. The difficult choice of chemotherapy in patients with unresectable non-small-cell lung cancer. Support Care Cancer  2000 ; 8: 223 -8. Google Scholar 221 Claessens MT, Lynn J, Zhong Z, Desbiens NA, Phillips RS, Wu AW, et al. Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments. J Am Geriatr Soc  2000 ; 48(5 Suppl): S146 -53. Google Scholar 222 McCarthy EP, Phillips RS, Zhong Z, Drews RE, Lynn J. Dying with cancer: patients' function, symptoms, and care preferences as death approaches. J Am Geriatr Soc  2000 ; 48(5 Suppl): S110 -21. Google Scholar 223 Quirt CF, Mackillop WJ, Ginsburg AD, Sheldon L, Brundage M, Dixon P, et al. Do doctors know when their patients don't? A survey of doctor-patient communication in lung cancer. Lung Cancer  1997 ; 18: 1 -20. Google Scholar 224 Sell L, Devlin B, Bourke SJ, Munro NC, Corris PA, Gibson GJ. Communicating the diagnosis of lung cancer. Respir Med  1993 ; 87: 61 -3. Google Scholar 225 Gamble K. Communication and information: the experience of radiotherapy patients. Eur J Cancer Care (Engl)  1998 ; 7: 153 -61. Google Scholar © Oxford University Press

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