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Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China

Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management... Hindawi Journal of Oncology Volume 2022, Article ID 7531545, 10 pages https://doi.org/10.1155/2022/7531545 Research Article Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China Yening Zhang, Zimeng Li, Ying Pang, Yi He, Shuangzhi He, Zhongge Su, Yuhe Zhou, Yan Wang, Bingmei Wang, Lili Song, Jinjiang Li, Xinkun Han, Chengcheng Zhou, Xiumin Li, and Lili Tang Department of Psycho-Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China Correspondence should be addressed to Lili Tang; tanglili_cpos@126.com Received 26 May 2022; Revised 4 August 2022; Accepted 20 August 2022; Published 16 September 2022 Academic Editor: Yingming Sun Copyright © 2022 Yening Zhang et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. �e integration of patient-reported health status has been increasingly emphasised for delivering high-quality care to advanced cancer patients. �is research is designed to track health status changes over time in Chinese advanced cancer patients to explore the risk factors a‡ecting their health status. Methods. Advanced cancer patients were recruited from Peking University Cancer Hospital. An electronic patient-reported outcome (ePRO) system with validated measurements was used to collect the data. ANOVA, the chi-square test, the nonparametric Kruskal–Wallis H test, and generalized estimating equation (GEE) analysis were used for the data analysis. Results. One hundred and three patients completed a baseline survey (T = 0) and two follow-up surveys (T1 = 14 days, T2 = 28 days). Chi-square test results indicate a signiœcant decrease in the percentage of patients reporting moderate or severe dižculty experienced by patients in terms of mobility, pain/discomfort, and anxiety/depression. However, there is a signiœcant increase in the percentage of patients reporting moderate or severe dižculty in self-care and usual activities. Scores on the visual analogue scale in the EQ-5D-5L instrument (EQ-VAS) are associated with patients’ income, and the degree of moderate or severe anxiety/depression is found to be associated with employment status. �e GEE results show that pain, loss of appetite, poor walking status e‡ected by symptoms, depression, and anxiety has worsened the health status. Conclusions. �e health status of Chinese advanced cancer patients under ePRO follow-up in China signiœcantly improves in the physical and psychological dimensions, accompanied by a decrease in usual activities and self-care. Routine screening and rational supportive care are recommended in oncology for cancer care. Based on the rational application of ePRO, longitudinal studies exploring the potential mechanisms of health status changing would provide more beneœcial guidance for improving the quality of life in patients with advanced cancer. to manage in this population [5, 6]. Quality of life (QoL) or 1. Background health status improvement is the primary objective of high- Cancer patients experience subjective distress induced by quality care for advanced cancer patients. Studies on cancer- various symptoms related to both the disease itself and related mechanisms, patient-reported outcome (PRO) treatment-related adverse events [1, 2]. �ough the œve-year monitoring, and multidisciplinary interventions for im- survival rate for cancer in China has increased from 30.9% proving QoL in this population have been reported in recorded in 2003 to 40.5% in 2015 [3], it is still lower than the various research publications. Recurrent or persistent in- rates in developed countries [4]. Available data indicate that ¬ammation is a common factor in the pathogenesis of approximately 60% of cancer will progress to the advanced neoplasia [7], and QoL is associated with systemic in- stages; symptom burden would be complicated and dižcult ¬ammation in patients with advanced cancer (based on PRO 2 Journal of Oncology with anticancer treatments. Second, the extant research does measurements) [8]. Some supportive interventions have been proven to improve QoL by modulating inflammatory not include longitudinal studies and none of the studies monitor changes in the health status of advanced cancer mediators [9, 10]. PRO monitoring of subjective symptoms in advanced cancer patients will provide a detailed map of patients. )erefore, the objectives of this study are as follows: health status changes and is recommended in the clinical (1) to track changes in health status over time in Chinese practice guidelines on palliative care of the National advanced cancer patients registered on multiple ePRO QoL Comprehensive Cancer Network (NCCN) [11]. PRO that assessment platforms, (2) to examine discrepancies in the includes health status is also viewed as a crucial indicator of EQ-5D-5L results in patients with different demographic treatment effectiveness in clinical trials and is an essential and medical condition, and (3) to explore risk factors that influence the changing of health status in advanced cancer criterion for drug approval, as required by the U.S Food and Drug Administration (FDA) from 2006 [12]. However, both patients. physical and psychosocial symptoms can adversely affect QoL and daily functions [13]. Research shows that im- 2. Materials and Methods provement in the QoL of patients is of great significance for their anticancer treatments, long-term rehabilitation, and )is longitudinal study was conducted at Peking University survival. Kypriotakis et al. indicated that advanced cancer Cancer Hospital. Patients who visited the symptom man- patients’ longitudinal experience of QoL is a significant agement clinic at Peking University Cancer Hospital be- prognostic factor for survival [14]. tween June 1st to December 31st, 2019 were recruited as Describing the changing trends in the health status, participants in the study on their initial visit. )e inclusion exploring the mechanisms behind fluctuating symptoms, criteria were as follows: (1) aged≥ 18 years old; (2) diagnosis and designing efficient interventions for advanced cancer of an advanced cancer (UICC TNM classification stage III patients would be particularly beneficial for improving QoL without curative treatment chance and stage IV), including of this population. )ere have been several longitudinal lung cancer, gastric cancer, oesophageal cancer, liver cancer, studies focused on cancer patients. Van Dijk-Lokkart et al. colorectal cancer, and breast cancer; (3) able to sign in- reported that cancer-related fatigue can improve after formed consent; and (4) could understand the items. Pa- treatment in children diagnosed with cancer, which is tients were excluded if they had a history of severe mental a favourable prognosis for a subsequent increase in physical disorders or major communication difficulties. )e study was activity [15]. For cancer patients undergoing pelvic/ab- approved by the Institutional Research Board (IRB) of Peking dominal radiotherapy, effectively managing nausea resulted University Cancer Hospital (approval number 2019YJZ07). in improved sleep [16]. Findings from a follow-up study indicated that QoL became worse for head and neck cancer (HNC) patients after cancer treatment [17]. Another study 2.1. Measures. EQ-5D-5L. )e EQ-5D-5L instrument reports that the QoL of early-stage patients with non-small comprises a short descriptive system questionnaire and cell lung cancer deteriorated six weeks after video-assisted a visual analogue scale (EQ-VAS) [24]. Each respondent is thoracoscopic lung resection and had improved by asked to choose a digital number that best describes their 12 months after the surgery [18]. A few of these studies focus health status for the day on each of the five dimensions, and specifically on changes in QoL in advanced cancer patients. the response for each health status dimension is assigned )e study by Contogni et al. focuses on changes in QoL in a five-digit code. )e EQ-5D-5L health status results are then advanced cancer patients on parenteral nutrition (HPN) converted into a single index value for China [25]. )e EQ [19]. Deteriorating nutrition status would negatively influ- VAS records the self-rated overall health status of the re- ence QoL in advanced colorectal cancer [20]. Based on spondent. )e EQ-5D-5L instrument is used to assess the a longitudinal study, Rojas-Concha suggests that the QoL of participants’ health status on the day of evaluation. )e advanced cancer patients in Chile could benefit from pal- EQ-5D is a preference-based measure of health status and liative care [21]. Research on the longitudinal health status of QoL used worldwide in clinical trials, population studies and patients with advanced cancer is of particularly crucial real-world clinical settings. It was developed from the EQ- clinical significance, especially for those who no longer have 5D-3L [24], the EQ-5D-3L was introduced in the 1990s [26], the opportunity for effective anticancer treatments. comprises five dimensions: mobility (MO), self-care (SC), We conducted this study based on a hypothesis drawn usual activities (UA), pain/discomfort (PD), and anxiety/ from research studies by Bash et al., which has indicated that depression (AD) and has three levels in each dimension: no PRO symptom monitoring is beneficial for the QoL and problems, some problems, and extreme problems. Although eventual survival of advanced cancer patients [22, 23]. widely used in the clinical trials, the EQ-5D-3L instrument Hence, we are conducting a pilot study to assess whether also has several limitations; for example, it is not sensitive to significant improvements in QoL can be tracked in Chinese mild health changes and it suffers from ceiling effects [27]. advanced cancer patients using PRO monitoring. )ere are To solve the issues, a new five-level EQ-5D (EQ-5D-5L) still a few knowledge gaps in the literature on this area of instrument was developed by the EuroQol Group. It remains research in China. First, previous national studies are either the original dimension and expands the number of levels of on a single cancer type or have cancer survivors as partic- severity in each dimension from three to five: no problems, ipants and hence cannot be generalized to advanced cancer slight problems, moderate problems, severe problems, and patients whose cancers are unlikely to be cured or controlled unable to/extreme problems; thus defining 3,125(55) distinct Journal of Oncology 3 T1 (Day 14) and T2 (Day 28), on which the patients received health statuses. )e EQ VAS records the self-rated health status valuation of the respondent on a vertical visual an- a reminder message from the ePRO system to complete the follow-up assessment via mobile phone. If the participant alogue scale, with the end points labelled ‘)e best health you can imagine’ (100 score) and ‘)e worst health you can had moderate-to-severe physical and psychological symp- imagine’ (0 score). )e measurement results of the EQ- toms, both the patients and the doctors were immediately 5D-5L instrument can be used to generate health utility sent alerts: reminding the patients to visit the clinic promptly values using value sets. It is generally suggested that different and informing the doctors to make timely adjustments to the value sets reflect the health preferences of people in different patient’s medication. countries. Currently, many countries, including China, have developed EQ-5D-5L value sets based on the health pref- 2.3. Statistical Analysis. )e EQ-5D-5L results were cal- erences of their respective populations [25, 28, 29]. We used culated following the user guide by the EuroQol Research the EQ-5D-5L tariff suggested by Liu in this study [30]. Foundation [35]. )e frequencies and proportions of the )e Chinese version of the MD Anderson Symptom EQ-5D-5L dimensions and levels are presented using de- Inventory (MDASI-C). It is a widely used multisymptom scriptive analysis. Moderate-to-severe difficulty was de- inventory with 19 items (13 items for symptom severity and fined as a dimension-level score of ≥3. )e overall health six items for life interference) rated on a 0–10 scale on which status was measured using the EQ VAS, employing mean 0 = nothing and 10 = most severe. MDASI-C is used to assess and standard deviation. )e EQ-5D-5L index was calcu- the symptom severity and the degree of life interference over lated using the Chinese value set and presented as the mean the past 24 hours. As proposed by Cleenland et al., mod- and standard deviation values. To explore discrepancies in erate-to-severe symptoms were defined as scores of ≥5 on the EQ-5D-5L results recorded over time against de- the MDASI [6]. )e MDASI-C has passed reliability and mography and medical data, chi-square tests were used, validity tests and can be used to measure the severity of along with one-way ANOVA (if the homogeneity of var- multiple symptoms and their impact on function [31]. iance assumption was satisfied) and the nonparametric )e Hospital Anxiety and Depression Scale (HADS). It Kruskal–Wallis H test (if homogeneity of variance as- has 14 items, with a 0–3 score range for each item. It is used sumption was not satisfied). Generalized estimated equa- to measure the anxiety and depression symptoms of patients tion (GEE) analysis was applied to repeated measures of over the past two weeks and is a relatively complete as- EQ-5D-5L and to explore the risk factors for changes in sessment with good reliability and validity [32]. health status. All demographic information, medical data, )e case report form (CRF). It captures the following: (1) and MDASI-C and HADS data were included in the GEE demographic and social economic information, such as age, model. )e statistical analyses were all conducted using sex, occupation, education, marital status, and medical SPSS 25.0 (IBM Corporation). payments; (2) disease data, such as information on disease diagnosis, staging, treatment, and medication; (3) )e Charlson Comorbidity Index (CCI) [33] is used to evaluate 3. Results complications that have a significant impact on the survival 3.1. Demography, Medical Data, and Other Descriptive Results and prognosis of cancer patients. at Baseline. One hundred-and-sixty-one advanced cancer )e Eastern Cooperative Oncology Group Performance patients were recruited as participants and completed in- Status (ECOG-PS) scale. It is a widely used tool for mea- formed consent, with 156 participants completing the survey suring the current functional status of cancer patients on five at baseline, 126 participants completing the first two surveys levels [34]: 0 = normal with no limitations; 1 = not my and 103 participants completing all three surveys (flowchart normal self, but able to be up and about with fairly normal shown in Figure 1). )e mean age of our sample was activities; 2 = not feeling up to most things, but in bed or 56.22± 10.898, with most of these individuals being middle- chair less than half the day; 3 = able to do little activity and aged and elderly (age≥ 45) (n � 125, 55.7%), living with spend most of the day in bed or chair; and 4 = pretty much a spouse (n � 147, 94.2%), and having their medical costs bedridden, rarely out of bed. covered by a government-pay scheme or a medical insurance policy (n � 129, 82.7%). Half the patients with cancer have 2.2. Data Collection. All data were collected on Day 0 (T0), a progress duration of less than half a year. )e results of the Day 14 (T1), and Day 28 (T2) after initial recruitment via an one-way ANOVA and nonparametric Kruskal–Wallis H test electrical PRO (ePRO) system developed by the researchers, indicate that discrepancies in the EQ-5D-5L dimension with participants completing the baseline assessment under responses correspond to specific demographic characteris- the guidance of research assistants. Several assessments and tics. )ere was a significant discrepancy in the EQ-5D-5L training sessions were held for research assistants, and their VAS mean scores of patients with different incomes: patients competence (especially evaluation consistency) was evalu- with an income of 15,000 Yuan per month and higher re- ated before commencing the study. )e symptom man- ported poorer health status (measured via VAS scores) than agement clinic of Peking University Cancer Hospital those with lower incomes. Furthermore, there was a signif- requires patients to make a follow-up visit every 14 days. icant discrepancy in the Dimension 5 (anxiety/depression) )us, we designed the follow-up time points of the study as responses of patients with different employment statuses: 4 Journal of Oncology 4. Discussion Outpatients contacted (N=205) 4.1.MainFindings. )e EQ-5D-5L has been used extensively Declined to participate to explore health status among different populations. We (N=44) found that health status scores among advanced cancer patients (VAS score: 58.35, index value: 0.614) were sig- Completed informed consent (N=161) nificantly lower than the norm scores of the Chinese pop- ulation (VAS score: 85.4, index value: 0.932) [36] and those Declined to complete the screening (N=5) of cancer survivors in general (VAS score: 70.35, index value: 0.841) [35]. Su et al. report that lung cancer patients have the Completed T0 screening (N=156) lowest health-related QoL compared to other cancer patients Declined to complete the [37]. However, in our study sample, we found no discrep- screening (N=30) ancies between advanced cancer patients with different di- Completed T1 screening agnoses. Several recent studies have shown that the health (N=126) status is increasingly viewed as a predictor of survival [38]. Declined to complete the )is was confirmed by Kypriotakis et al. with respect to screening (N=23) advanced cancer patients; they concluded that longitudinal experience of health status is a significant prognostic factor Completed T2 screening (N=103) for survival and holds important implications for medical decision-making concerning advanced cancer patients [14]. Figure 1: Study flowchart. If health status monitoring is indeed beneficial for survival, it would be more adoptable—from the perspective of health unemployed patients reported higher levels of anxiety/de- economics—than expensive anticancer treatments. Dis- crepancies in health status were found among patients with pression than those employed (Table 1). )e top five symptoms reported as moderate-to-severe by different demographics and medical data. Patients with monthly incomes of 15,000 Yuan per month and higher advanced cancer patients are as follows: fatigue (61.5%), insomnia (60.9%), pain (58.3%), distress (53.2%), and loss of appetite reported poorer health statuses, as reflected by their EQ- 5D-5L VAS scores, than those with lower incomes. )is (46.8%). 57.1% of the participants reported experiencing signif- icant mood distress via the HADS (score of≥ 15). finding is similar to one of the findings in the research by Tribius, who reports that locally advanced HNC patients with a high socioeconomic status reported worse QoL than 3.2. Health Status Measured via EQ-5D-5L at Baseline and similar patients with a low economic status [39]. Further- Trends at 3ree Time Points. Significant discrepancy was more, a larger proportion of unemployed patients reported found via the chi-square test between the three time moderate problems on the anxiety/depression dimension points, T0 vs. T2 and T1 vs. T2. Responses with moderate than patients who were employed. By contrast, Morrison and severe difficulty changed significantly in the following reports that lung cancer patients are more likely to report dimensions: decreased in mobility (three time points, emotional problems upon diagnosis if they are employed 2 2 2 χ = 84.541; T1 vs.T2, χ = 60.438; T0 vs.T2, χ = 55.060; [40]. Discrepancies may also occur because the compared p< 0.001), pain/discomfort (three time points, samples are different, which indicates that the nature of the 2 2 2 χ = 136.303; T1 vs.T2, χ = 88.542; T0 vs.T2, χ = 99.651; emotional challenges experienced by advanced cancer pa- p< 0.001); and anxiety/depression (three time points, tients is different from those experienced by other 2 2 2 χ = 91.625; T1 vs.T2, χ = 60.027; T0 vs.T2, χ = 64.254; populations. p< 0.001) dimensions; but increased in self-care (three Symptoms, function and mood can significantly influ- 2 2 time points, χ = 50.202; T1 vs.T2, χ = 33.052; T0 vs.T2, ence the health status among advanced cancer patients. In χ = 29.277; p< 0.001), and usual activities (three time our study, pain, poor walking status effected by symptoms, 2 2 points, χ = 78.562; T1 vs.T2, χ = 53.007; T0 vs.T2, and anxiety/depression are risk factors that significantly χ = 48.228; p< 0.001) dimensions (Table 2). )e mean influence the health status of advanced cancer patients. Pain scores of the EQ-5D-5L index and the VAS values at the is a factor influencing poor health status, which calls for three time points improved slightly but not significantly more attention to pain management for advanced cancer (Table 2). patients, as indicated by the high prevalence of pain in our sample (58.3%). Walking status effected by symptoms has also been confirmed as another factor for low health status 3.3.RiskFactorsforHealthStatusfromtheLongitudinalStudy. by Laird et al., who reported that, among advanced cancer )e results from the GEE model show that ECOG-PS scores patients, performance status is strongly associated with (OR = 0.910, p< 0.001), pain (OR = 0.984, p � 0.005), poor deteriorating QoL parameters [8]. Dunn et al. indicated that walking status effected by symptoms (OR = 0.972, advanced melanoma patients have more significantly de- p< 0.001), and anxiety/depression (OR = 0.991, p< 0.001) creased emotional function than patients with a localised were risk factors, which were strongly associated with form of the disease. A high proportion of patients in our changes in the health status of patients with advanced sample reported significant psychological distress, which is cancer (Table 3). Journal of Oncology 5 Table 1: Demographic information, medical data, and distribution of EQ-5D-5L dimension responses (% of responses with moderate problems—i.e., Level 3—and above) as a function of various demographic characteristics. Usual Pain/ Anxiety/ Demographic N (%)/M± SD Mobility Self-care EQ-5D-5L index activities discomfort Depression VAS M (SD) characteristics (N � 156) N (%) N (%) M (SD) N (%) N (%) N (%) Age (years) 56.22± 10.898 ≤44 23 (14.7) 6 (26.1) 3 (13.0) 6 (26.1) 9 (39.1) 10 (43.5) 0.67 (0.33) 61.78 (24.34) 45–59 64 (41.0) 20 (31.3) 6 (9.4) 17 (26.6) 43 (67.2) 26 (40.6) 0.59 (0.31) 56.58 (23.36) ≥60 61 (39.1) 20 (32.8) 9 (14.8) 20 (32.8) 35 (57.4) 17 (27.9) 0.63 (0.31) 59.10 (21.00) Missing 8 (5.1) P value 0.355 0.616 0.818 0.060 0.072 0.606 0.610 Sex Male 86 (55.1) 23 (26.7) 8 (9.3) 21 (24.4) 51 (59.3) 28 (32.6) 0.65 (0.29) 60.26 (20.45) Female 69 (44.2) 26 (36.2) 12 (17.4) 24 (34.8) 41 (59.4) 29 (42.0) 0.58 (0.35) 55.48 (23.91) Missing 1 (0.6) P value 0.529 0.815 0.193 0.527 0.148 0.378 0.263 Marital status Without partner (single, separated, divorced, or widowed) 8 (5.1) 44 (29.9) 19 (12.9) 42 (28.6) 88 (59.9) 55 (37.4) 0.61 (0.32) 57.98 (22.41) With spouse 147 (94.2) 4 (50.0) 1 (12.5) 3 (37.5) 4 (50.0) 2 (25.0) 0.61 (0.37) 60.88 (16.39) Missing 1 (0.6) P value 0.233 0.972 0.589 0.581 0.480 0.737 0.742 Education level Junior, middle school, and lower 49 (31.4) 12 (24.5) 6 (12.2) 11 (22.4) 31 (63.3) 17 (34.7) 0.63 (0.30) 57.57 (23.08) High middle school and special secondary school 45 (28.8) 15 (33.3) 7 (15.6) 17 (37.8) 26 (57.8) 18 (40.0) 0.59 (0.35) 56.16 (23.91) Junior college and above 61 (39.1) 21 (34.4) 7 (11.5) 17 (27.9) 35 (57.4) 22 (36.1) 0.63 (0.31) 60.03 (20.01) Missing 1 (0.6) P value 0.494 0.815 0.256 0.797 0.859 0.794 0.659 Average family income <5,000 Yuan/month 42 (26.9) 13 (31.0) 5 (11.9) 14 (33.3) 26 (61.9) 19 (45.2) 0.60 (0.30) 58.67 (20.31) 5,000–10,000 Yuan/month 50 (32.1) 13 (26.0) 7 (14.0) 12 (24.0) 29 (58.0) 15 (30.0) 0.65 (0.33) 60.36 (22.10) 10,000–15,000 Yuan/month 40 (25.6) 14 (35.0) 4 (10.0) 11 (27.5) 22 (55.0) 11 (27.5) 0.63 (0.30) 61.55 (21.66) 15000 Yuan/month and above 23 (14.7) 8 (34.8) 4 (17.4) 8 (34.8) 15 (65.2) 12 (52.2) 0.53 (0.37) 46.35 (23.56) Missing 1 (0.6) P value 0.794 0.850 0.706 0.852 0.108 0.516 p � 0.044 Medical cost coverage Government-pay/Medical insurance 129 (82.7) 40 (31.0) 15 (11.6) 38 (29.5) 74 (57.4) 45 (34.9) 0.63 (0.31) 59.17 (22.74) Self-pay 26 (16.7) 8 (30.8) 5 (19.2) 7 (26.9) 18 (69.2) 12 (46.2) 0.55 (0.34) 52.96 (18.17) Missing 1 (0.6) P value 0.981 0.293 0.796 0.263 0.278 0.161 0.159 Employment status Retired 54 (34.6) 17 (34.5) 9 (16.7) 19 (35.2) 33 (61.1) 19 (35.2) 0.60 (0.34) 59.46 (22.39) Employed 71 (45.5) 22 (31.0) 5 (7.0) 16 (22.5) 38 (53.5) 20 (28.2) 0.66 (0.28) 60.20 (22.49) Without work 28 (17.9) 9 (32.1) 5 (17.9) 8 (28.6) 20 (71.4) 17 (60.7) 0.52 (0.36) 50.11 (20.03) Missing 3 (91.9) P value 0.994 0.172 0.299 0.253 p � 0.010 0.138 0.107 Cancer site 6 Journal of Oncology Table 1: Continued. Usual Pain/ Anxiety/ Demographic N (%)/M± SD Mobility Self-care EQ-5D-5L index activities discomfort Depression VAS M (SD) characteristics (N � 156) N (%) N (%) M (SD) N (%) N (%) N (%) Breast 18 (11.5) 7 (38.9) 5 (27.8) 8 (44.4) 9 (50.0) 9 (50.0) 0.51 (0.44) 55.28 (28.44) Gastric 21 (13.5) 2 (10.0) 1 (5.0) 1 (5.0) 7 (35.0) 5 (25.0) 0.78 (0.19) 59.05 (19.15) Oesophageal 10 (6.4) 4 (36.4) 1 (9.1) 4 (36.4) 8 (72.7) 5 (45.5) 0.58 (0.31) 62.45 (19.86) Liver 12 (7.7) 4 (33.3) 0 (0) 2 (16.7) 9 (75.0) 3 (33.3) 0.67 (0.23) 64.75 (19.86) Lung 49 (31.4) 17 (34.7) 8 (16.3) 17 (34.7) 34 (69.4) 18 (36.7) 0.58 (0.30) 56.37 (23.14) Colorectal 47 (30.1) 15 (32.6) 5 (10.9) 13 (28.3) 26 (56.5) 16 (34.8) 0.62 (0.33) 58.70 (20.55) P value 0.114 0.214 0.305 0.491 0.155 0.127 0.834 Duration of cancer progression (days) <Half years 66 (42.3) 20 (30.3) 11 (16.7) 20 (30.3) 39 (59.1) 27 (40.9) 0.59 (0.35) 56.23 (21.86) Half to less than one year 35 (22.4) 14 (40.0) 3 (8.6) 11 (31.4) 23 (65.7) 14 (40.0) 0.59 (0.31) 60.97 (18.80) Longer than one year 40 (25.6) 12 (30.0) 6 (15.0) 12 (30.0) 24 (60.0) 12 (30.0) 0.62 (0.29) 55.15 (25.27) Missing 15 (9.6) P value 0.384 0.335 0.781 0.807 0.353 0.840 0.404 Oncology therapies No 63 (40.4) 21 (33.3) 9 (14.3) 17 (27.0) 44 (69.8) 22 (34.9) 0.60 (0.32) 58.83 (20.86) Yes 91 (58.3) 27 (29.7) 11 (12.1) 28 (30.8) 48 (52.7) 34 (37.4) 0.62 (0.32) 57.74 (23.14) Missing 2 (1.3) P value 0.394 0.303 0.893 0.106 0.839 0.566 0.981 NS: Not significant. p< 0.05 duration of cancer progression (days): it is the duration between the time when filling out the questionnaires and the time of diagnosis of cancer progression. One-way ANOVA was applied if the homogeneity of variance assumption was satisfied, and the non-parametric Kruskal–Wallis H test was utilised if the homogeneity of variance assumption was not satisfied. Journal of Oncology 7 Table 2: Distribution of EQ-5D-5L dimension responses at three time points (T0, T1, and T2) and chi-square test results reporting the percentage of patients with moderate and severe problems across three time points. 2 2 2 T0 N (%)/M T1 N (%)/M T2 N (%)/M Chi-square (T0, T1, T2) (χ , P)/ Chi-square (T1, T2) (χ , P)/ Chi-square (T0, T2) (χ , P)/ Dimensions (SD) (SD) (SD) One-way ANOVA One-way ANOVA One-way ANOVA Mobility No problems and slight 74 (71.8) 69 (67.0) 77 (74.8) problems (level≤ 2) ∗∗ 2 2 2 ∗∗ ∗∗ χ � 84.541 p< 0.001 χ � 60.438 p< 0.001 χ � 55.060 p< 0.001 Moderate, severe problems, and 29 (28.2) 34 (33.0) 26 (25.2) unable to do (level≥ 3) Self-care No problems and slight 92 (89.3) 88 (85.4) 85 (82.5) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ � 50.202 p< 0.001 χ � 33.052 p< 0.001 χ � 29.277 p< 0.001 Moderate, severe problems, and 11 (10.7) 15 (14.6) 18 (17.5) unable to do (level≥ 3) Usual activities No problems and slight 82 (79.6) 77 (74.8) 76 (73.8) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ � 78.562 p< 0.001 χ � 53.007 p< 0.001 χ � 48.228 p< 0.001 Moderate, severe problems, and 21 (20.4) 26 (25.2) 27 (26.2) unable to do (level≥ 3) Pain/Discomfort No problems and slight 46 (44.7) 55 (53.4) 63 (61.2) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ �136.303 p< 0.001 χ � 88.542 p< 0.001 χ � 99.651 p< 0.001 Moderate, severe problems, and 57 (55.3) 48 (46.6) 40 (38.8) unable to do (level≥ 3) Anxiety/Depression No problems and slight 68 (66.0) 72 (69.9) 74 (71.8) problems (level≤ 2) 2 ∗∗ 2 ∗∗ 2 ∗∗ χ � 91.625 p< 0.001 χ � 60.027 p< 0.001 χ � 64.254 p< 0.001 Moderate, severe problems, and 35 (34.0) 31 (30.1) 29 (28.2) unable to do (level≥ 3) 0.623 EQ-5D-5L index value 0.614 (0.318) 0.660 (0.323) F � 0.093 p � 0.911 F � 0.155 p � 0.694 F � 0.114 p � 0.736 (0.330) 58.35 61.79 62.28 VAS F � 1.145 p � 0.320 F � 0.027 p � 0.870 F � 1.813 p � 0.180 (22.205) (21.207) (22.832) ∗∗ p< 0.01. Chi-square tests were used for categorical variables, while ANOVA tests were used for continuous variables. 8 Journal of Oncology Table 3: Results from the GEE model. Parameter estimates 95% Wald 95% Wald confidence Hypothesis test confidence interval interval for Exp Parameter B Std. Error Exp (B) (B) Lower Upper Wald chi-square df Sig. Lower Upper (Intercept) 1.127 0.0653 1.000 1.255 298.209 1 0.000 3.088 2.717 3.509 ECOG-PS −0.094 0.0138 −0.121 −0.067 46.754 1 0.000 0.910 0.886 0.935 Pain −0.016 0.0047 −0.025 −0.007 11.630 1 0.001 0.984 0.975 0.993 Walking −0.028 0.0078 −0.044 −0.013 13.185 1 0.000 0.972 0.957 0.987 HADS −0.009 0.0015 −0.012 −0.006 34.462 1 0.000 0.991 0.988 0.994 (Scale) 0.033 Dependent variable: EQ-5D-5L index score model: (Intercept), age range, disease duration range, sex, job, race, marital status, education, income, medical coverage, diagnosis, treatment, ECOG-PS, symptoms and interference (pain, fatigue, nausea, insomnia, distress, shortness of breath, memory, appetite, drowsy, dry mouth, sadness, vomiting, numbness, constipation, general activity, mood, work, relationship, walking, enjoyment), anxiety/depression from HADS, Time (baseline, T1-two week follow-up, T2-four week follow-up). an independent risk factor for deteriorating health status. Inflammation is one of the key factors that modulate cancer pain, as proinflammatory cytokines and chemokines mod- High-quality supportive care for advanced cancer patients should be a key part of the strategies in the dimensions of ulate neuronal activity. Corticosteroids can relieve pain symptom management, performance status improvement, when administered as anti-inflammatory drugs [43]. Both and psychosocial care. physical and psychological symptoms associated with in- In this longitudinal research, health status changes were flammation are independent risk factors for fluctuating captured via sensitive EQ-5D-5L screening, with results health status. Furthermore, inflammation negatively impacts indicating that symptom monitoring is of great significance cancer prognosis, which is associated with diminished QoL to rational symptom management. Changes in the health [44]. )e results of this research have also inspired us to status were captured at three time points, with significant further investigate the fluctuation of inflammatory media- tors in relation to changing in health status among patients changes occurring between T0 and T2 and between T1 and T2, but not between T0 and T1. )is indicates that in ad- with advanced cancer. vanced cancer patients, significant health changes may occur approximately one month. In this study, all participants 4.2. Limitations. )e limitations of this study are as fol- utilised the ePRO auto-symptom management system. lows: the sample size is small and the study was conducted Symptom alerts, triggered by a score of≥7 (severe symptom at a single centre. A multicenter study with a more rep- burden) on each symptom scale in the MDASI, would resentative sample is recommended for future research. appear in patients’ ePRO terminals, prompting these pa- )is longitudinal study was designed primarily to in- tients to counsel with research coordinators and receive vestigate changes in health status among advanced cancer symptom management knowledge, if they so choose. In our patients; hence, a comparison group was not concluded. study, pain, anxiety and depression can improve with timely However, we compared our results against those of the adjustments of symptoms management informed by the normal Chinese population and cancer survivors. )e ePRO system. )is is supported by the findings of Basch findings of this study indicate that advanced cancer pa- et al., who concluded that advanced cancer patients receiving tients could benefit from routine health status monitoring. symptom monitoring are admitted to the emergency room )erefore, we recommend that a random clinical trial less often, remain on chemotherapy longer and have a longer designed specifically to investigate the benefits of the quality-adjusted survival rate than those who do not receive ePRO system to the health status of advanced cancer symptom monitoring [22]. Furthermore, overall improve- patients be conducted. ment in the survival rate has been confirmed via a clinical trial: 31.2 months among the PRO group vs. 26.0 months 4.3. Clinical Implications. For advanced cancer patients, among the usual care group [23]. It is necessary to explore curative care is not the dominant medical strategy. However, whether the benefits would be derived from ePRO system this population would benefit more from supportive care implementation in terms of the health status and survival in that focuses on how to improve the patient’s health status. It Chinese advanced cancer patients. is necessary to monitor the health status of advanced cancer Many studies have proved that common symptoms with patients using a validated ePRO platform and to develop a high prevalence among cancer patients are modulated by individualised supportive care protocols. Pain management, inflammation, patients with high C-reactive protein (CRP) improving mobility, and psychosocial care for anxiety and levels are at greater odds of experiencing fatigue [41], and depression should be incorporated into supportive care significantly high levels of vegetative depression are strongly protocols. linked to elevated levels of interleukin-6 (IL-6) [42]. Journal of Oncology 9 [5] D. H. Henry, H. N. Viswanathan, E. P. Elkin, S. Traina, 5. Conclusion S. Wade, and D. Cella, “Symptoms and treatment burden Monitoring the health status of advanced cancer patients associated with cancer treatment: results from a cross- and developing individualised supportive care protocols are sectional national survey in the U.S,” Supportive Care in Cancer, vol. 16, no. 7, pp. 791–801, 2008. imperative for positive outcomes. )e EQ-5D-5L is a useful [6] C. S. Cleeland, F. Zhao, V. T. Chang et al., “)e symptom tool for recording patients’ health status via dimension burden of cancer: Evidence for a core set of cancer-related and responses, index scores and the VAS, as well as for capturing treatment-related symptoms from the Eastern Cooperative changes in the health status over time under reasonable Oncology Group Symptom Outcomes and Practice Patterns symptom management or supportive care. )e risk factors study,” Cancer, vol. 119, no. 24, pp. 4333–4340, 2013. for deteriorating health status can serve as useful references [7] D. Schottenfeld and J. Beebe-Dimmer, “Chronic in- for health status management in advanced cancer patients, flammation: a common and important factor in the patho- especially for symptom management. genesis of neoplasia,” CA: A Cancer Journal for Clinicians, vol. 56, no. 2, pp. 69–83, 2006. Data Availability [8] B. J. Laird, M. Fallon, M. J. Hjermstad et al., “Quality of life in patients with advanced cancer: Differential association with All data supporting the findings of this study and all sup- performance status and systemic inflammatory response,” plementary materials are available from the corresponding Journal of Clinical Oncology, vol. 34, no. 23, pp. 2769–2775, author upon reasonable request. [9] M. Fillon, “Changes in inflammation and insulin pathways mediate the association between resistance training and breast Consent cancer survival,” CA: A Cancer Journal for Clinicians, vol. 68, no. 3, pp. 175–177, 2018. Written informed consent was obtained from all [10] B. Oh, P. N. Butow, B. A. Mullan et al., “Effect of medical participants. 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Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China

Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China

Abstract

<i>Objectives</i>. The integration of patient-reported health status has been increasingly emphasised for delivering high-quality care to advanced cancer patients. This research is designed to track health status changes over time in Chinese advanced cancer patients to explore the risk factors affecting their health status. <i>Methods</i>. Advanced cancer patients were recruited from Peking University Cancer Hospital. An electronic patient-reported outcome (ePRO) system with validated measurements was used to collect the data. ANOVA, the chi-square test, the nonparametric Kruskal&#x2013;Wallis H test, and generalized estimating equation (GEE) analysis were used for the data analysis. <i>Results</i>. One hundred and three patients completed a baseline survey (<i>T</i>&#x2009;=&#x2009;0) and two follow-up surveys (<i>T</i>1&#x2009;=&#x2009;14 days, <i>T</i>2&#x2009;=&#x2009;28 days). Chi-square test results indicate a significant decrease in the percentage of patients reporting moderate or severe difficulty experienced by patients in terms of mobility, pain/discomfort, and anxiety/depression. However, there is a significant increase in the percentage of patients reporting moderate or severe difficulty in self-care and usual activities. Scores on the visual analogue scale in the EQ-5D-5L instrument (EQ-VAS) are associated with patients&#x2019; income, and the degree of moderate or severe anxiety/depression is found to be associated with employment status. The GEE results show that pain, loss of appetite, poor walking status effected by symptoms, depression, and anxiety has worsened the health status. <i>Conclusions</i>. The health status of Chinese advanced cancer patients under ePRO follow-up in China significantly improves in the physical and psychological dimensions, accompanied by a decrease in usual activities and self-care. Routine screening and rational supportive care are recommended in oncology for cancer care. Based on the rational application of ePRO, longitudinal studies exploring the potential mechanisms of health status changing would provide more beneficial guidance for improving the quality of life in patients with advanced cancer.

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10.1155/2022/7531545
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Abstract

Hindawi Journal of Oncology Volume 2022, Article ID 7531545, 10 pages https://doi.org/10.1155/2022/7531545 Research Article Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China Yening Zhang, Zimeng Li, Ying Pang, Yi He, Shuangzhi He, Zhongge Su, Yuhe Zhou, Yan Wang, Bingmei Wang, Lili Song, Jinjiang Li, Xinkun Han, Chengcheng Zhou, Xiumin Li, and Lili Tang Department of Psycho-Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China Correspondence should be addressed to Lili Tang; tanglili_cpos@126.com Received 26 May 2022; Revised 4 August 2022; Accepted 20 August 2022; Published 16 September 2022 Academic Editor: Yingming Sun Copyright © 2022 Yening Zhang et al. �is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. �e integration of patient-reported health status has been increasingly emphasised for delivering high-quality care to advanced cancer patients. �is research is designed to track health status changes over time in Chinese advanced cancer patients to explore the risk factors a‡ecting their health status. Methods. Advanced cancer patients were recruited from Peking University Cancer Hospital. An electronic patient-reported outcome (ePRO) system with validated measurements was used to collect the data. ANOVA, the chi-square test, the nonparametric Kruskal–Wallis H test, and generalized estimating equation (GEE) analysis were used for the data analysis. Results. One hundred and three patients completed a baseline survey (T = 0) and two follow-up surveys (T1 = 14 days, T2 = 28 days). Chi-square test results indicate a signiœcant decrease in the percentage of patients reporting moderate or severe dižculty experienced by patients in terms of mobility, pain/discomfort, and anxiety/depression. However, there is a signiœcant increase in the percentage of patients reporting moderate or severe dižculty in self-care and usual activities. Scores on the visual analogue scale in the EQ-5D-5L instrument (EQ-VAS) are associated with patients’ income, and the degree of moderate or severe anxiety/depression is found to be associated with employment status. �e GEE results show that pain, loss of appetite, poor walking status e‡ected by symptoms, depression, and anxiety has worsened the health status. Conclusions. �e health status of Chinese advanced cancer patients under ePRO follow-up in China signiœcantly improves in the physical and psychological dimensions, accompanied by a decrease in usual activities and self-care. Routine screening and rational supportive care are recommended in oncology for cancer care. Based on the rational application of ePRO, longitudinal studies exploring the potential mechanisms of health status changing would provide more beneœcial guidance for improving the quality of life in patients with advanced cancer. to manage in this population [5, 6]. Quality of life (QoL) or 1. Background health status improvement is the primary objective of high- Cancer patients experience subjective distress induced by quality care for advanced cancer patients. Studies on cancer- various symptoms related to both the disease itself and related mechanisms, patient-reported outcome (PRO) treatment-related adverse events [1, 2]. �ough the œve-year monitoring, and multidisciplinary interventions for im- survival rate for cancer in China has increased from 30.9% proving QoL in this population have been reported in recorded in 2003 to 40.5% in 2015 [3], it is still lower than the various research publications. Recurrent or persistent in- rates in developed countries [4]. Available data indicate that ¬ammation is a common factor in the pathogenesis of approximately 60% of cancer will progress to the advanced neoplasia [7], and QoL is associated with systemic in- stages; symptom burden would be complicated and dižcult ¬ammation in patients with advanced cancer (based on PRO 2 Journal of Oncology with anticancer treatments. Second, the extant research does measurements) [8]. Some supportive interventions have been proven to improve QoL by modulating inflammatory not include longitudinal studies and none of the studies monitor changes in the health status of advanced cancer mediators [9, 10]. PRO monitoring of subjective symptoms in advanced cancer patients will provide a detailed map of patients. )erefore, the objectives of this study are as follows: health status changes and is recommended in the clinical (1) to track changes in health status over time in Chinese practice guidelines on palliative care of the National advanced cancer patients registered on multiple ePRO QoL Comprehensive Cancer Network (NCCN) [11]. PRO that assessment platforms, (2) to examine discrepancies in the includes health status is also viewed as a crucial indicator of EQ-5D-5L results in patients with different demographic treatment effectiveness in clinical trials and is an essential and medical condition, and (3) to explore risk factors that influence the changing of health status in advanced cancer criterion for drug approval, as required by the U.S Food and Drug Administration (FDA) from 2006 [12]. However, both patients. physical and psychosocial symptoms can adversely affect QoL and daily functions [13]. Research shows that im- 2. Materials and Methods provement in the QoL of patients is of great significance for their anticancer treatments, long-term rehabilitation, and )is longitudinal study was conducted at Peking University survival. Kypriotakis et al. indicated that advanced cancer Cancer Hospital. Patients who visited the symptom man- patients’ longitudinal experience of QoL is a significant agement clinic at Peking University Cancer Hospital be- prognostic factor for survival [14]. tween June 1st to December 31st, 2019 were recruited as Describing the changing trends in the health status, participants in the study on their initial visit. )e inclusion exploring the mechanisms behind fluctuating symptoms, criteria were as follows: (1) aged≥ 18 years old; (2) diagnosis and designing efficient interventions for advanced cancer of an advanced cancer (UICC TNM classification stage III patients would be particularly beneficial for improving QoL without curative treatment chance and stage IV), including of this population. )ere have been several longitudinal lung cancer, gastric cancer, oesophageal cancer, liver cancer, studies focused on cancer patients. Van Dijk-Lokkart et al. colorectal cancer, and breast cancer; (3) able to sign in- reported that cancer-related fatigue can improve after formed consent; and (4) could understand the items. Pa- treatment in children diagnosed with cancer, which is tients were excluded if they had a history of severe mental a favourable prognosis for a subsequent increase in physical disorders or major communication difficulties. )e study was activity [15]. For cancer patients undergoing pelvic/ab- approved by the Institutional Research Board (IRB) of Peking dominal radiotherapy, effectively managing nausea resulted University Cancer Hospital (approval number 2019YJZ07). in improved sleep [16]. Findings from a follow-up study indicated that QoL became worse for head and neck cancer (HNC) patients after cancer treatment [17]. Another study 2.1. Measures. EQ-5D-5L. )e EQ-5D-5L instrument reports that the QoL of early-stage patients with non-small comprises a short descriptive system questionnaire and cell lung cancer deteriorated six weeks after video-assisted a visual analogue scale (EQ-VAS) [24]. Each respondent is thoracoscopic lung resection and had improved by asked to choose a digital number that best describes their 12 months after the surgery [18]. A few of these studies focus health status for the day on each of the five dimensions, and specifically on changes in QoL in advanced cancer patients. the response for each health status dimension is assigned )e study by Contogni et al. focuses on changes in QoL in a five-digit code. )e EQ-5D-5L health status results are then advanced cancer patients on parenteral nutrition (HPN) converted into a single index value for China [25]. )e EQ [19]. Deteriorating nutrition status would negatively influ- VAS records the self-rated overall health status of the re- ence QoL in advanced colorectal cancer [20]. Based on spondent. )e EQ-5D-5L instrument is used to assess the a longitudinal study, Rojas-Concha suggests that the QoL of participants’ health status on the day of evaluation. )e advanced cancer patients in Chile could benefit from pal- EQ-5D is a preference-based measure of health status and liative care [21]. Research on the longitudinal health status of QoL used worldwide in clinical trials, population studies and patients with advanced cancer is of particularly crucial real-world clinical settings. It was developed from the EQ- clinical significance, especially for those who no longer have 5D-3L [24], the EQ-5D-3L was introduced in the 1990s [26], the opportunity for effective anticancer treatments. comprises five dimensions: mobility (MO), self-care (SC), We conducted this study based on a hypothesis drawn usual activities (UA), pain/discomfort (PD), and anxiety/ from research studies by Bash et al., which has indicated that depression (AD) and has three levels in each dimension: no PRO symptom monitoring is beneficial for the QoL and problems, some problems, and extreme problems. Although eventual survival of advanced cancer patients [22, 23]. widely used in the clinical trials, the EQ-5D-3L instrument Hence, we are conducting a pilot study to assess whether also has several limitations; for example, it is not sensitive to significant improvements in QoL can be tracked in Chinese mild health changes and it suffers from ceiling effects [27]. advanced cancer patients using PRO monitoring. )ere are To solve the issues, a new five-level EQ-5D (EQ-5D-5L) still a few knowledge gaps in the literature on this area of instrument was developed by the EuroQol Group. It remains research in China. First, previous national studies are either the original dimension and expands the number of levels of on a single cancer type or have cancer survivors as partic- severity in each dimension from three to five: no problems, ipants and hence cannot be generalized to advanced cancer slight problems, moderate problems, severe problems, and patients whose cancers are unlikely to be cured or controlled unable to/extreme problems; thus defining 3,125(55) distinct Journal of Oncology 3 T1 (Day 14) and T2 (Day 28), on which the patients received health statuses. )e EQ VAS records the self-rated health status valuation of the respondent on a vertical visual an- a reminder message from the ePRO system to complete the follow-up assessment via mobile phone. If the participant alogue scale, with the end points labelled ‘)e best health you can imagine’ (100 score) and ‘)e worst health you can had moderate-to-severe physical and psychological symp- imagine’ (0 score). )e measurement results of the EQ- toms, both the patients and the doctors were immediately 5D-5L instrument can be used to generate health utility sent alerts: reminding the patients to visit the clinic promptly values using value sets. It is generally suggested that different and informing the doctors to make timely adjustments to the value sets reflect the health preferences of people in different patient’s medication. countries. Currently, many countries, including China, have developed EQ-5D-5L value sets based on the health pref- 2.3. Statistical Analysis. )e EQ-5D-5L results were cal- erences of their respective populations [25, 28, 29]. We used culated following the user guide by the EuroQol Research the EQ-5D-5L tariff suggested by Liu in this study [30]. Foundation [35]. )e frequencies and proportions of the )e Chinese version of the MD Anderson Symptom EQ-5D-5L dimensions and levels are presented using de- Inventory (MDASI-C). It is a widely used multisymptom scriptive analysis. Moderate-to-severe difficulty was de- inventory with 19 items (13 items for symptom severity and fined as a dimension-level score of ≥3. )e overall health six items for life interference) rated on a 0–10 scale on which status was measured using the EQ VAS, employing mean 0 = nothing and 10 = most severe. MDASI-C is used to assess and standard deviation. )e EQ-5D-5L index was calcu- the symptom severity and the degree of life interference over lated using the Chinese value set and presented as the mean the past 24 hours. As proposed by Cleenland et al., mod- and standard deviation values. To explore discrepancies in erate-to-severe symptoms were defined as scores of ≥5 on the EQ-5D-5L results recorded over time against de- the MDASI [6]. )e MDASI-C has passed reliability and mography and medical data, chi-square tests were used, validity tests and can be used to measure the severity of along with one-way ANOVA (if the homogeneity of var- multiple symptoms and their impact on function [31]. iance assumption was satisfied) and the nonparametric )e Hospital Anxiety and Depression Scale (HADS). It Kruskal–Wallis H test (if homogeneity of variance as- has 14 items, with a 0–3 score range for each item. It is used sumption was not satisfied). Generalized estimated equa- to measure the anxiety and depression symptoms of patients tion (GEE) analysis was applied to repeated measures of over the past two weeks and is a relatively complete as- EQ-5D-5L and to explore the risk factors for changes in sessment with good reliability and validity [32]. health status. All demographic information, medical data, )e case report form (CRF). It captures the following: (1) and MDASI-C and HADS data were included in the GEE demographic and social economic information, such as age, model. )e statistical analyses were all conducted using sex, occupation, education, marital status, and medical SPSS 25.0 (IBM Corporation). payments; (2) disease data, such as information on disease diagnosis, staging, treatment, and medication; (3) )e Charlson Comorbidity Index (CCI) [33] is used to evaluate 3. Results complications that have a significant impact on the survival 3.1. Demography, Medical Data, and Other Descriptive Results and prognosis of cancer patients. at Baseline. One hundred-and-sixty-one advanced cancer )e Eastern Cooperative Oncology Group Performance patients were recruited as participants and completed in- Status (ECOG-PS) scale. It is a widely used tool for mea- formed consent, with 156 participants completing the survey suring the current functional status of cancer patients on five at baseline, 126 participants completing the first two surveys levels [34]: 0 = normal with no limitations; 1 = not my and 103 participants completing all three surveys (flowchart normal self, but able to be up and about with fairly normal shown in Figure 1). )e mean age of our sample was activities; 2 = not feeling up to most things, but in bed or 56.22± 10.898, with most of these individuals being middle- chair less than half the day; 3 = able to do little activity and aged and elderly (age≥ 45) (n � 125, 55.7%), living with spend most of the day in bed or chair; and 4 = pretty much a spouse (n � 147, 94.2%), and having their medical costs bedridden, rarely out of bed. covered by a government-pay scheme or a medical insurance policy (n � 129, 82.7%). Half the patients with cancer have 2.2. Data Collection. All data were collected on Day 0 (T0), a progress duration of less than half a year. )e results of the Day 14 (T1), and Day 28 (T2) after initial recruitment via an one-way ANOVA and nonparametric Kruskal–Wallis H test electrical PRO (ePRO) system developed by the researchers, indicate that discrepancies in the EQ-5D-5L dimension with participants completing the baseline assessment under responses correspond to specific demographic characteris- the guidance of research assistants. Several assessments and tics. )ere was a significant discrepancy in the EQ-5D-5L training sessions were held for research assistants, and their VAS mean scores of patients with different incomes: patients competence (especially evaluation consistency) was evalu- with an income of 15,000 Yuan per month and higher re- ated before commencing the study. )e symptom man- ported poorer health status (measured via VAS scores) than agement clinic of Peking University Cancer Hospital those with lower incomes. Furthermore, there was a signif- requires patients to make a follow-up visit every 14 days. icant discrepancy in the Dimension 5 (anxiety/depression) )us, we designed the follow-up time points of the study as responses of patients with different employment statuses: 4 Journal of Oncology 4. Discussion Outpatients contacted (N=205) 4.1.MainFindings. )e EQ-5D-5L has been used extensively Declined to participate to explore health status among different populations. We (N=44) found that health status scores among advanced cancer patients (VAS score: 58.35, index value: 0.614) were sig- Completed informed consent (N=161) nificantly lower than the norm scores of the Chinese pop- ulation (VAS score: 85.4, index value: 0.932) [36] and those Declined to complete the screening (N=5) of cancer survivors in general (VAS score: 70.35, index value: 0.841) [35]. Su et al. report that lung cancer patients have the Completed T0 screening (N=156) lowest health-related QoL compared to other cancer patients Declined to complete the [37]. However, in our study sample, we found no discrep- screening (N=30) ancies between advanced cancer patients with different di- Completed T1 screening agnoses. Several recent studies have shown that the health (N=126) status is increasingly viewed as a predictor of survival [38]. Declined to complete the )is was confirmed by Kypriotakis et al. with respect to screening (N=23) advanced cancer patients; they concluded that longitudinal experience of health status is a significant prognostic factor Completed T2 screening (N=103) for survival and holds important implications for medical decision-making concerning advanced cancer patients [14]. Figure 1: Study flowchart. If health status monitoring is indeed beneficial for survival, it would be more adoptable—from the perspective of health unemployed patients reported higher levels of anxiety/de- economics—than expensive anticancer treatments. Dis- crepancies in health status were found among patients with pression than those employed (Table 1). )e top five symptoms reported as moderate-to-severe by different demographics and medical data. Patients with monthly incomes of 15,000 Yuan per month and higher advanced cancer patients are as follows: fatigue (61.5%), insomnia (60.9%), pain (58.3%), distress (53.2%), and loss of appetite reported poorer health statuses, as reflected by their EQ- 5D-5L VAS scores, than those with lower incomes. )is (46.8%). 57.1% of the participants reported experiencing signif- icant mood distress via the HADS (score of≥ 15). finding is similar to one of the findings in the research by Tribius, who reports that locally advanced HNC patients with a high socioeconomic status reported worse QoL than 3.2. Health Status Measured via EQ-5D-5L at Baseline and similar patients with a low economic status [39]. Further- Trends at 3ree Time Points. Significant discrepancy was more, a larger proportion of unemployed patients reported found via the chi-square test between the three time moderate problems on the anxiety/depression dimension points, T0 vs. T2 and T1 vs. T2. Responses with moderate than patients who were employed. By contrast, Morrison and severe difficulty changed significantly in the following reports that lung cancer patients are more likely to report dimensions: decreased in mobility (three time points, emotional problems upon diagnosis if they are employed 2 2 2 χ = 84.541; T1 vs.T2, χ = 60.438; T0 vs.T2, χ = 55.060; [40]. Discrepancies may also occur because the compared p< 0.001), pain/discomfort (three time points, samples are different, which indicates that the nature of the 2 2 2 χ = 136.303; T1 vs.T2, χ = 88.542; T0 vs.T2, χ = 99.651; emotional challenges experienced by advanced cancer pa- p< 0.001); and anxiety/depression (three time points, tients is different from those experienced by other 2 2 2 χ = 91.625; T1 vs.T2, χ = 60.027; T0 vs.T2, χ = 64.254; populations. p< 0.001) dimensions; but increased in self-care (three Symptoms, function and mood can significantly influ- 2 2 time points, χ = 50.202; T1 vs.T2, χ = 33.052; T0 vs.T2, ence the health status among advanced cancer patients. In χ = 29.277; p< 0.001), and usual activities (three time our study, pain, poor walking status effected by symptoms, 2 2 points, χ = 78.562; T1 vs.T2, χ = 53.007; T0 vs.T2, and anxiety/depression are risk factors that significantly χ = 48.228; p< 0.001) dimensions (Table 2). )e mean influence the health status of advanced cancer patients. Pain scores of the EQ-5D-5L index and the VAS values at the is a factor influencing poor health status, which calls for three time points improved slightly but not significantly more attention to pain management for advanced cancer (Table 2). patients, as indicated by the high prevalence of pain in our sample (58.3%). Walking status effected by symptoms has also been confirmed as another factor for low health status 3.3.RiskFactorsforHealthStatusfromtheLongitudinalStudy. by Laird et al., who reported that, among advanced cancer )e results from the GEE model show that ECOG-PS scores patients, performance status is strongly associated with (OR = 0.910, p< 0.001), pain (OR = 0.984, p � 0.005), poor deteriorating QoL parameters [8]. Dunn et al. indicated that walking status effected by symptoms (OR = 0.972, advanced melanoma patients have more significantly de- p< 0.001), and anxiety/depression (OR = 0.991, p< 0.001) creased emotional function than patients with a localised were risk factors, which were strongly associated with form of the disease. A high proportion of patients in our changes in the health status of patients with advanced sample reported significant psychological distress, which is cancer (Table 3). Journal of Oncology 5 Table 1: Demographic information, medical data, and distribution of EQ-5D-5L dimension responses (% of responses with moderate problems—i.e., Level 3—and above) as a function of various demographic characteristics. Usual Pain/ Anxiety/ Demographic N (%)/M± SD Mobility Self-care EQ-5D-5L index activities discomfort Depression VAS M (SD) characteristics (N � 156) N (%) N (%) M (SD) N (%) N (%) N (%) Age (years) 56.22± 10.898 ≤44 23 (14.7) 6 (26.1) 3 (13.0) 6 (26.1) 9 (39.1) 10 (43.5) 0.67 (0.33) 61.78 (24.34) 45–59 64 (41.0) 20 (31.3) 6 (9.4) 17 (26.6) 43 (67.2) 26 (40.6) 0.59 (0.31) 56.58 (23.36) ≥60 61 (39.1) 20 (32.8) 9 (14.8) 20 (32.8) 35 (57.4) 17 (27.9) 0.63 (0.31) 59.10 (21.00) Missing 8 (5.1) P value 0.355 0.616 0.818 0.060 0.072 0.606 0.610 Sex Male 86 (55.1) 23 (26.7) 8 (9.3) 21 (24.4) 51 (59.3) 28 (32.6) 0.65 (0.29) 60.26 (20.45) Female 69 (44.2) 26 (36.2) 12 (17.4) 24 (34.8) 41 (59.4) 29 (42.0) 0.58 (0.35) 55.48 (23.91) Missing 1 (0.6) P value 0.529 0.815 0.193 0.527 0.148 0.378 0.263 Marital status Without partner (single, separated, divorced, or widowed) 8 (5.1) 44 (29.9) 19 (12.9) 42 (28.6) 88 (59.9) 55 (37.4) 0.61 (0.32) 57.98 (22.41) With spouse 147 (94.2) 4 (50.0) 1 (12.5) 3 (37.5) 4 (50.0) 2 (25.0) 0.61 (0.37) 60.88 (16.39) Missing 1 (0.6) P value 0.233 0.972 0.589 0.581 0.480 0.737 0.742 Education level Junior, middle school, and lower 49 (31.4) 12 (24.5) 6 (12.2) 11 (22.4) 31 (63.3) 17 (34.7) 0.63 (0.30) 57.57 (23.08) High middle school and special secondary school 45 (28.8) 15 (33.3) 7 (15.6) 17 (37.8) 26 (57.8) 18 (40.0) 0.59 (0.35) 56.16 (23.91) Junior college and above 61 (39.1) 21 (34.4) 7 (11.5) 17 (27.9) 35 (57.4) 22 (36.1) 0.63 (0.31) 60.03 (20.01) Missing 1 (0.6) P value 0.494 0.815 0.256 0.797 0.859 0.794 0.659 Average family income <5,000 Yuan/month 42 (26.9) 13 (31.0) 5 (11.9) 14 (33.3) 26 (61.9) 19 (45.2) 0.60 (0.30) 58.67 (20.31) 5,000–10,000 Yuan/month 50 (32.1) 13 (26.0) 7 (14.0) 12 (24.0) 29 (58.0) 15 (30.0) 0.65 (0.33) 60.36 (22.10) 10,000–15,000 Yuan/month 40 (25.6) 14 (35.0) 4 (10.0) 11 (27.5) 22 (55.0) 11 (27.5) 0.63 (0.30) 61.55 (21.66) 15000 Yuan/month and above 23 (14.7) 8 (34.8) 4 (17.4) 8 (34.8) 15 (65.2) 12 (52.2) 0.53 (0.37) 46.35 (23.56) Missing 1 (0.6) P value 0.794 0.850 0.706 0.852 0.108 0.516 p � 0.044 Medical cost coverage Government-pay/Medical insurance 129 (82.7) 40 (31.0) 15 (11.6) 38 (29.5) 74 (57.4) 45 (34.9) 0.63 (0.31) 59.17 (22.74) Self-pay 26 (16.7) 8 (30.8) 5 (19.2) 7 (26.9) 18 (69.2) 12 (46.2) 0.55 (0.34) 52.96 (18.17) Missing 1 (0.6) P value 0.981 0.293 0.796 0.263 0.278 0.161 0.159 Employment status Retired 54 (34.6) 17 (34.5) 9 (16.7) 19 (35.2) 33 (61.1) 19 (35.2) 0.60 (0.34) 59.46 (22.39) Employed 71 (45.5) 22 (31.0) 5 (7.0) 16 (22.5) 38 (53.5) 20 (28.2) 0.66 (0.28) 60.20 (22.49) Without work 28 (17.9) 9 (32.1) 5 (17.9) 8 (28.6) 20 (71.4) 17 (60.7) 0.52 (0.36) 50.11 (20.03) Missing 3 (91.9) P value 0.994 0.172 0.299 0.253 p � 0.010 0.138 0.107 Cancer site 6 Journal of Oncology Table 1: Continued. Usual Pain/ Anxiety/ Demographic N (%)/M± SD Mobility Self-care EQ-5D-5L index activities discomfort Depression VAS M (SD) characteristics (N � 156) N (%) N (%) M (SD) N (%) N (%) N (%) Breast 18 (11.5) 7 (38.9) 5 (27.8) 8 (44.4) 9 (50.0) 9 (50.0) 0.51 (0.44) 55.28 (28.44) Gastric 21 (13.5) 2 (10.0) 1 (5.0) 1 (5.0) 7 (35.0) 5 (25.0) 0.78 (0.19) 59.05 (19.15) Oesophageal 10 (6.4) 4 (36.4) 1 (9.1) 4 (36.4) 8 (72.7) 5 (45.5) 0.58 (0.31) 62.45 (19.86) Liver 12 (7.7) 4 (33.3) 0 (0) 2 (16.7) 9 (75.0) 3 (33.3) 0.67 (0.23) 64.75 (19.86) Lung 49 (31.4) 17 (34.7) 8 (16.3) 17 (34.7) 34 (69.4) 18 (36.7) 0.58 (0.30) 56.37 (23.14) Colorectal 47 (30.1) 15 (32.6) 5 (10.9) 13 (28.3) 26 (56.5) 16 (34.8) 0.62 (0.33) 58.70 (20.55) P value 0.114 0.214 0.305 0.491 0.155 0.127 0.834 Duration of cancer progression (days) <Half years 66 (42.3) 20 (30.3) 11 (16.7) 20 (30.3) 39 (59.1) 27 (40.9) 0.59 (0.35) 56.23 (21.86) Half to less than one year 35 (22.4) 14 (40.0) 3 (8.6) 11 (31.4) 23 (65.7) 14 (40.0) 0.59 (0.31) 60.97 (18.80) Longer than one year 40 (25.6) 12 (30.0) 6 (15.0) 12 (30.0) 24 (60.0) 12 (30.0) 0.62 (0.29) 55.15 (25.27) Missing 15 (9.6) P value 0.384 0.335 0.781 0.807 0.353 0.840 0.404 Oncology therapies No 63 (40.4) 21 (33.3) 9 (14.3) 17 (27.0) 44 (69.8) 22 (34.9) 0.60 (0.32) 58.83 (20.86) Yes 91 (58.3) 27 (29.7) 11 (12.1) 28 (30.8) 48 (52.7) 34 (37.4) 0.62 (0.32) 57.74 (23.14) Missing 2 (1.3) P value 0.394 0.303 0.893 0.106 0.839 0.566 0.981 NS: Not significant. p< 0.05 duration of cancer progression (days): it is the duration between the time when filling out the questionnaires and the time of diagnosis of cancer progression. One-way ANOVA was applied if the homogeneity of variance assumption was satisfied, and the non-parametric Kruskal–Wallis H test was utilised if the homogeneity of variance assumption was not satisfied. Journal of Oncology 7 Table 2: Distribution of EQ-5D-5L dimension responses at three time points (T0, T1, and T2) and chi-square test results reporting the percentage of patients with moderate and severe problems across three time points. 2 2 2 T0 N (%)/M T1 N (%)/M T2 N (%)/M Chi-square (T0, T1, T2) (χ , P)/ Chi-square (T1, T2) (χ , P)/ Chi-square (T0, T2) (χ , P)/ Dimensions (SD) (SD) (SD) One-way ANOVA One-way ANOVA One-way ANOVA Mobility No problems and slight 74 (71.8) 69 (67.0) 77 (74.8) problems (level≤ 2) ∗∗ 2 2 2 ∗∗ ∗∗ χ � 84.541 p< 0.001 χ � 60.438 p< 0.001 χ � 55.060 p< 0.001 Moderate, severe problems, and 29 (28.2) 34 (33.0) 26 (25.2) unable to do (level≥ 3) Self-care No problems and slight 92 (89.3) 88 (85.4) 85 (82.5) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ � 50.202 p< 0.001 χ � 33.052 p< 0.001 χ � 29.277 p< 0.001 Moderate, severe problems, and 11 (10.7) 15 (14.6) 18 (17.5) unable to do (level≥ 3) Usual activities No problems and slight 82 (79.6) 77 (74.8) 76 (73.8) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ � 78.562 p< 0.001 χ � 53.007 p< 0.001 χ � 48.228 p< 0.001 Moderate, severe problems, and 21 (20.4) 26 (25.2) 27 (26.2) unable to do (level≥ 3) Pain/Discomfort No problems and slight 46 (44.7) 55 (53.4) 63 (61.2) problems (level≤ 2) 2 2 2 ∗∗ ∗∗ ∗∗ χ �136.303 p< 0.001 χ � 88.542 p< 0.001 χ � 99.651 p< 0.001 Moderate, severe problems, and 57 (55.3) 48 (46.6) 40 (38.8) unable to do (level≥ 3) Anxiety/Depression No problems and slight 68 (66.0) 72 (69.9) 74 (71.8) problems (level≤ 2) 2 ∗∗ 2 ∗∗ 2 ∗∗ χ � 91.625 p< 0.001 χ � 60.027 p< 0.001 χ � 64.254 p< 0.001 Moderate, severe problems, and 35 (34.0) 31 (30.1) 29 (28.2) unable to do (level≥ 3) 0.623 EQ-5D-5L index value 0.614 (0.318) 0.660 (0.323) F � 0.093 p � 0.911 F � 0.155 p � 0.694 F � 0.114 p � 0.736 (0.330) 58.35 61.79 62.28 VAS F � 1.145 p � 0.320 F � 0.027 p � 0.870 F � 1.813 p � 0.180 (22.205) (21.207) (22.832) ∗∗ p< 0.01. Chi-square tests were used for categorical variables, while ANOVA tests were used for continuous variables. 8 Journal of Oncology Table 3: Results from the GEE model. Parameter estimates 95% Wald 95% Wald confidence Hypothesis test confidence interval interval for Exp Parameter B Std. Error Exp (B) (B) Lower Upper Wald chi-square df Sig. Lower Upper (Intercept) 1.127 0.0653 1.000 1.255 298.209 1 0.000 3.088 2.717 3.509 ECOG-PS −0.094 0.0138 −0.121 −0.067 46.754 1 0.000 0.910 0.886 0.935 Pain −0.016 0.0047 −0.025 −0.007 11.630 1 0.001 0.984 0.975 0.993 Walking −0.028 0.0078 −0.044 −0.013 13.185 1 0.000 0.972 0.957 0.987 HADS −0.009 0.0015 −0.012 −0.006 34.462 1 0.000 0.991 0.988 0.994 (Scale) 0.033 Dependent variable: EQ-5D-5L index score model: (Intercept), age range, disease duration range, sex, job, race, marital status, education, income, medical coverage, diagnosis, treatment, ECOG-PS, symptoms and interference (pain, fatigue, nausea, insomnia, distress, shortness of breath, memory, appetite, drowsy, dry mouth, sadness, vomiting, numbness, constipation, general activity, mood, work, relationship, walking, enjoyment), anxiety/depression from HADS, Time (baseline, T1-two week follow-up, T2-four week follow-up). an independent risk factor for deteriorating health status. Inflammation is one of the key factors that modulate cancer pain, as proinflammatory cytokines and chemokines mod- High-quality supportive care for advanced cancer patients should be a key part of the strategies in the dimensions of ulate neuronal activity. Corticosteroids can relieve pain symptom management, performance status improvement, when administered as anti-inflammatory drugs [43]. Both and psychosocial care. physical and psychological symptoms associated with in- In this longitudinal research, health status changes were flammation are independent risk factors for fluctuating captured via sensitive EQ-5D-5L screening, with results health status. Furthermore, inflammation negatively impacts indicating that symptom monitoring is of great significance cancer prognosis, which is associated with diminished QoL to rational symptom management. Changes in the health [44]. )e results of this research have also inspired us to status were captured at three time points, with significant further investigate the fluctuation of inflammatory media- tors in relation to changing in health status among patients changes occurring between T0 and T2 and between T1 and T2, but not between T0 and T1. )is indicates that in ad- with advanced cancer. vanced cancer patients, significant health changes may occur approximately one month. In this study, all participants 4.2. Limitations. )e limitations of this study are as fol- utilised the ePRO auto-symptom management system. lows: the sample size is small and the study was conducted Symptom alerts, triggered by a score of≥7 (severe symptom at a single centre. A multicenter study with a more rep- burden) on each symptom scale in the MDASI, would resentative sample is recommended for future research. appear in patients’ ePRO terminals, prompting these pa- )is longitudinal study was designed primarily to in- tients to counsel with research coordinators and receive vestigate changes in health status among advanced cancer symptom management knowledge, if they so choose. In our patients; hence, a comparison group was not concluded. study, pain, anxiety and depression can improve with timely However, we compared our results against those of the adjustments of symptoms management informed by the normal Chinese population and cancer survivors. )e ePRO system. )is is supported by the findings of Basch findings of this study indicate that advanced cancer pa- et al., who concluded that advanced cancer patients receiving tients could benefit from routine health status monitoring. symptom monitoring are admitted to the emergency room )erefore, we recommend that a random clinical trial less often, remain on chemotherapy longer and have a longer designed specifically to investigate the benefits of the quality-adjusted survival rate than those who do not receive ePRO system to the health status of advanced cancer symptom monitoring [22]. Furthermore, overall improve- patients be conducted. ment in the survival rate has been confirmed via a clinical trial: 31.2 months among the PRO group vs. 26.0 months 4.3. Clinical Implications. For advanced cancer patients, among the usual care group [23]. It is necessary to explore curative care is not the dominant medical strategy. However, whether the benefits would be derived from ePRO system this population would benefit more from supportive care implementation in terms of the health status and survival in that focuses on how to improve the patient’s health status. It Chinese advanced cancer patients. is necessary to monitor the health status of advanced cancer Many studies have proved that common symptoms with patients using a validated ePRO platform and to develop a high prevalence among cancer patients are modulated by individualised supportive care protocols. Pain management, inflammation, patients with high C-reactive protein (CRP) improving mobility, and psychosocial care for anxiety and levels are at greater odds of experiencing fatigue [41], and depression should be incorporated into supportive care significantly high levels of vegetative depression are strongly protocols. linked to elevated levels of interleukin-6 (IL-6) [42]. Journal of Oncology 9 [5] D. H. Henry, H. N. Viswanathan, E. P. Elkin, S. Traina, 5. Conclusion S. Wade, and D. Cella, “Symptoms and treatment burden Monitoring the health status of advanced cancer patients associated with cancer treatment: results from a cross- and developing individualised supportive care protocols are sectional national survey in the U.S,” Supportive Care in Cancer, vol. 16, no. 7, pp. 791–801, 2008. imperative for positive outcomes. )e EQ-5D-5L is a useful [6] C. S. Cleeland, F. Zhao, V. T. 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