Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

Milea J. M. Timbergen; Winette T. A. van der Graaf; Dirk J. Grünhagen; Eugenie Younger; Stefan Sleijfer; Alison Dunlop; Lucy Dean; Cornelis Verhoef; Lonneke V. van de Poll-Franse; Olga Husson

doi:10.1155/2020/2141939

Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

Timbergen, Milea J. M.;van der Graaf, Winette T. A.;Grünhagen, Dirk J.;Younger, Eugenie;Sleijfer, Stefan;Dunlop, Alison;Dean, Lucy;Verhoef, Cornelis;van de Poll-Franse, Lonneke V.;Husson, Olga 2020-07-26 00:00:00 Hindawi Sarcoma Volume 2020, Article ID 2141939, 9 pages https://doi.org/10.1155/2020/2141939 Research Article Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries 1,2 3,4 1 Milea J. M. Timbergen , Winette T. A. van der Graaf, Dirk J. Gru¨nhagen, 5,6 2 5 5 1 Eugenie Younger, Stefan Sleijfer, Alison Dunlop, Lucy Dean, Cornelis Verhoef, 7,8,9 3,5,6,7 Lonneke V. van de Poll-Franse, and Olga Husson Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Department of Medical Oncology, !e Netherlands Cancer Institute, Amsterdam, Netherlands Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, UK Division of Clinical Studies, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK Division of Psychosocial Research and Epidemiology, !e Netherlands Cancer Institute, Amsterdam, Netherlands Department of Medical and Clinical Psychology, Tilburg University, Netherlands Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, Netherlands Correspondence should be addressed to Milea J. M. Timbergen; m.timbergen@erasmusmc.nl Received 4 May 2020; Revised 27 June 2020; Accepted 29 June 2020; Published 26 July 2020 Academic Editor: Ajay Puri Copyright © 2020 Milea J. M. Timbergen 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. Purpose. Desmoid-type ﬁbromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of deﬁnitive treatments, and the chronic character of the disease can signiﬁcantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a speciﬁc HRQoL questionnaire for this patient group. Methods. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. Results. 'e most highly ranked issues by patients (n �29) were issues concerning “tumour growth,” “feeling that there is something in the body that does not belong there,” and “fear of tumour growth into adjacent tissues or organs” with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1–4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n �31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). Conclusion. 'is study identiﬁed the most relevant issues for DTF patients, which should be included in a DTF-speciﬁc HRQoL questionnaire. Additionally, we identiﬁed diﬀerences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to conﬁrm these ﬁndings and to devise a comprehensive and speciﬁc HRQoL questionnaire for DTF patients. Sporadic DTF arises in musculoaponeurotic structures with 1. Introduction the most common sites being the abdominal wall and the Sporadic desmoid-type ﬁbromatosis (DTF) is a rare, bor- extremities [4]. Symptoms vary, depending on tumour site, derline tumour of the soft tissues [1–3]. Most patients are size, and inﬁltration of adjacent structures, resulting in pain females,agedbetween 20and40 years atprimarydiagnosis [3]. and/or functional impairment. DTF does not metastasize, 2 Sarcoma rarely has fatal outcomes, often displays long periods of identiﬁed in the Dutch group. Next, issues were grouped spontaneous stabilisation, and can undergo spontaneous re- into categories and duplicate issues covering the same topics gression [5]. Surgical resection, radiotherapy, and non- were removed. A total of 124 issues were converted into a cytotoxic and cytotoxic systemic therapies may be considered provisional list of issues. All issues were reviewed by two in patients with symptomatic disease, but unfortunately, these authors (MT and OH). All issues were translated by native “traditional” treatment options do not guarantee tumour re- English and Dutch speakers. duction and/or clinical response [6]. Local recurrence after surgery remains high [7, 8], leading to a reduction in surgical treatments for DTF over recent decades [3, 4]. Additionally, 2.2. Patient Selection. Patients with DTF were approached for participation by their treating physician. Inclusion cri- “active” forms of treatment can be debilitating, causing greater morbidity than the tumour itself. For these reasons, active teria were histologically proven DTF, age ≥18 years, Dutch or English language skills, and a “recent” visit (<2 years) to surveillance is now recommended as a ﬁrst-line management for most patients with DTF [6, 9].'erefore, DTF has obtained the hospital. Exclusion criteria were participation in one of the previous focus groups or patient interviews and patients a “chronic” status and its impact on patients should be with a diagnosis of cancer or familial adenomatous polyposis evaluated accordingly. Health-related quality of life (HRQoL) provides infor- (FAP). Patients received an information letter which explained study objectives. Baseline characteristics and mation beyond traditional measures of eﬃcacy in oncology such as overall survival and is increasingly used as an details about the individual disease trajectory of participants were obtained. Patients were only invited to participate once endpoint in clinical trials [10, 11]. We previously performed a systematic literature review to evaluate which HRQoL and did not have to provide a reason if they declined. No reminders were sent. All data from patients was collected measures were used in research to assess HRQoL in DTF [12]. Generic HRQoL measures (e.g., the cancer-speciﬁc core and processed anonymously. questionnaire from European Organisation for Research and Treatment of Cancer; the EORTC Quality of Life Core 2.3. Selection of Healthcare Providers. To examine whether Questionnaire (EORTC QLQ-C30)) may not consider dis- HCPs with expertise and experience in sarcomas and DTF ease-speciﬁc issues in DTF patients. Site-speciﬁc tools (e.g., have the same perspectives as patients with DTF about key Toronto Extremity Salvage Score) may not be relevant to HRQoL issues, an e-survey of the same 124 issues was certain groups (e.g., those with abdominal wall or head and created using LimeSurvey Servicebedrijf© software. 'e neck tumours). issue list was available in two languages (Dutch and English), At present, there is no validated DTF-speciﬁc HRQoL and issues were presented in a random order. In the tool, and this was illustrated by a systematic literature review Netherlands, HCPs from the multidisciplinary team (e.g., published by our group [12, 13]. In order to gain greater surgeons, oncologists, radiologists, radiotherapists, sarcoma insight into the issues that patients with DTF experience in clinical nurse specialists, and physiotherapists) were iden- their daily lives, and to evaluate their experiences of tiﬁed using the website Orphanet, which provides infor- healthcare including the supportive care system, we previ- ously organised focus groups and semistructured interviews, mation on centres of expertise dedicated to the medical management for rare diseases (https://www.orpha.net/ in the United Kingdom (UK) and in the Netherlands (NL) consor/cgi-bin/Clinics_Search.php?lng�EN). In the UK, [12, 13]. 'ese studies identiﬁed issues covering various HCPs of the aforementioned disciplines were identiﬁed domains including the diagnostic pathway, the treatment using the sarcoma network group of the Royal Marsden pathway, daily limitations (e.g., physical and psychological Hospital, London, UK. Every HCP received an invitation symptoms), and experiences with the current healthcare email with a token and link to the e-survey. A reminder was system. sent after one week if the HCP had not responded. 'e main goal of this study was to determine the relative importance of each issue and receiving feedback on the appropriateness of content and breadth of coverage. In the 2.4. Sociodemographic and Clinical Characteristics. Age at present study, we used the previously identiﬁed issues to (1) the time of diagnosis was either stated by the patient or identify the most relevant issues to patients with DTF in two calculated using the date of birth and date of the ﬁrst pa- healthcare settings (UK and NL) and to (2) identify dif- thology report. Age at the time of questionnaire completion ferences in scores between both countries. was either stated by the patient or calculated using the date of informed consent and the date of birth. Education levels 2. Materials and Methods were categorized into “high” (PhD, university, and higher education postgraduate/undergraduate degree), “interme- 2.1. Identiﬁcation of Issues. 'e EORTC Quality of Life diate” (professional qualiﬁcation, vocational work, work- Group methodology for developing a questionnaire was related qualiﬁcation, general secondary education, and used for the selection of relevant issues based on previous further/intermediate education), and “low” (primary edu- focus groups and patients interviews [14]. Issues that had cation (with a higher, but not completed education) and previously been identiﬁed to be of concern to DTF patients secondary education). Continuous variables were presented were listed per country (UK and NL). A total of 188 issues as a mean with a standard deviation (SD) or as a median with were identiﬁed in the UK group and 110 issues were Sarcoma 3 age or sex) were excluded from the analysis. Diﬀerences in an interquartile range (IQR). Categorical variables were presented as number (n) using frequencies and percentages. priority scores (Dutch versus British participating patients and HCPs versus participating patients) and diﬀerences in scores of the EORTC QLQ-C30 scales between groups 2.5. Presentation of Issues to Patients and Healthcare (Dutch versus British participating patients and Dutch and Providers. A total of 124 issues were presented to patients British participating patients versus the Dutch and British and healthcare providers (HCPs) in a random order general population) were tested for their signiﬁcance using (Supplemental Table 1). Patients and HCPs scored 124 issues the Mann–Whitney U test. SPSS Statistics (version 24) was by relevance on a Likert scale from 1 to 4 ((1) not at all, (2) a used for the Mann–Whitney U tests (IBM, Armonk, New little, (3) quite a bit, and (4) very much) and ranked the top York, USA). Two-sided p<0.05 was considered statistically ten most important issues. 'e frequency that each issue signiﬁcant. appeared in the top ten most important issues was converted into the mean priority score (M-score) per issue. 'e fre- 3. Results quency of the top ten priority score of each issue was cal- culated and ranked in overall priority score. Where 3.1. PatientCohort. Forty-one patientsfrom the ErasmusMC, questions were left blank by the participant, they were coded Rotterdam, the Netherlands, and 32 patients from the Royal as a “missing value” and not incorporated in the total score. Marsden Hospital, London, UK, were approached during July Space for general remarks was available at the end of the and August 2018. Out of 73 patients, 29 patients (total re- questionnaire. sponse rate of 39.7%) gave written informed consent (Fig- ure 1). 'e cohort comprised of 10 males and 19 females with DTF most commonly localized in the extremities, ﬂank, and 2.6. EORTC QLQ-C30 Questionnaire. In addition to the chest wall (n �15, 52%). Nine participants had received active issue list, patients were asked to ﬁll out the 30-item EORTC treatment at the time of the questionnaire. 'e median, self- QLQ-C30 questionnaire (version 3) to assess HRQoL [15]. reported age at diagnosis was 38 years (IQR 30–48) (Table 1). Norm data were obtained from the EORTC, which recently Sociodemographic characteristics are summarized in Sup- collected data from the general population in Europe and plemental Table 1. All participants completed the issue list, and North America [16]. Only data from the general population sixteen participants ranked their top 10 most relevant issues. in the Netherlands and the UK were used for the current study. 'e EORTC QLQ-C30 questionnaire contains ﬁve functional scales (physical, role, cognitive, emotional, and 3.2. Ranking of Priority of the Issues. Ranking of HRQoL social functioning), a global health status scale, three issues revealed that 13 out of 124 issues (10.5%) were chosen symptom scales (fatigue, nausea and vomiting, and pain), to be the most relevant (prevalence ratio of >30%) (Table 2). and six single items (appetite loss, diarrhoea, dyspnoea, Patients considered the following issues as relevant and constipation, insomnia, and ﬁnancial diﬃculties). 'e missing on the current issue list: “problems with healthcare questionnaire has a 1-week time frame and uses a four-point insurances,” “coverage of costs related to the disease such as response format (“not at all,” “a little,” “quite a bit,” and traveling costs,” “lack of adequate online information,” “lack “very much”), with the exception of the global health status of knowledge about treatment options outside the region or scale, which has a seven-point response format. 'e scores country,” “lack of information about pain management and were calculated using linear transformation to a score be- referral to pain professionals,” and “lack of advice regarding tween 0 and 100. For the functional scales and the global dietary restrictions or playing sports.” A list of the missing health status, a high score represents a high (healthy) level of items, general remarks, and quotes is provided in Supple- functioning. A high score for the symptom scales represents mental Tables 3 and 4. a high level of symptoms (greater symptom burden) [17]. 'e EORTC QLQ-C30 summary score was calculated using the mean scores of the function scales and the reversed mean 3.3. British versus Dutch Patients. Overall, British patients scores of the symptom scales and single items (ﬁnancial gave higher scores for each issue compared to Dutch patients impact and global health status excluded) and is summarized (M-score 2.2 (UK) vs. M-score 1.5 (NL)) (Supplemental as the mean of the combined 13 QLQ-C30 scale scores. A Table 2). Diﬀerences in score of more than 1 point between higher summary score represented a better outcome [18, 19]. Dutch and British patients are displayed in Supplemental 'e summary score was only calculated when all of the Figure 1. Additionally, priority scores of Dutch and British required 13 scale and item scores were available. Data HCPs and scores of participating patients and HCPs from analysis and handling of missing items were done according the Netherlands and the UK were compared (Supplemental to the scoring manual of the EORTC [17]. Table 2). 'e total cohort of patients was too small to identify any diﬀerences between subgroups (e.g., initial treatment type, tumour location, and age at diagnosis). 2.7. Statistical Analysis. Patients were matched, using a 1:10 nearest-neighbour match method, with the general pop- ulation based on nationality, age, and sex using RStudio 3.4. Healthcare Providers. In the Netherlands, HCPs were (RStudio, version 1.0.153, Boston, MA, package MatchIt). invited to six sarcoma centres. All HCPs from the UK were Patients with missing values (lacking information regarding employees at the Royal Marsden Hospital, London. Twenty- 4 Sarcoma Patients Dutch patients British patients No response No response invited to invited to n = 24 n = 20 participate participate n = 41 n = 32 Completion of Completion of Response rate Response rate questionnaires questionnaires 41.5% 37.5% n = 17 n = 12 Completed questionnaires n = 29 Healthcare providers (HCPs) Dutch HCPs British HCPs No response No response invited to invited to n = 23 n = 12 participate participate n = 44 n = 22 Completion of Completion of Response rate Response rate questionnaires questionnaires 47.8% 45.5% n = 21 n = 10 Completed questionnaires n = 31 Figure 1: Flow diagram of participating patients and healthcare providers’ responses to this survey. prognosis” (M-score 2.9). Overall, HCPs from the UK gave one Dutch and ten British HCPs responded. Professional backgrounds included surgical oncologist (n �12), medical higher scores, compared to Dutch HCPs with M-scores of 2.8 oncologist (n �6), radiation oncologist (n �5), specialized and 2.0, respectively (Supplemental Table 2). sarcoma nurse (n �5), and other professions including a radiologist, physiotherapist, and pain specialist (all n �1). 3.5. Participating Patients versus Healthcare Providers. Seventeen professionals had more than 10 years of experi- 'ere was considerable overlap between the highest ranked ence, three had 6–10 years of experience, and eleven had 5 or issues according to patients and HCPs, particularly re- less years of experience working with desmoid patients. garding the unpredictable growth pattern of DTF tumours Frequency of contact with DTF patients varied between once (Supplemental Table 1). HCPs scored signiﬁcantly higher a week (n �9, 29%) to rarely (less than once every 3 months) (p<0.05) on 77 out of a total of 77 of 124 issues. HCPs also (n �1, 3%). gave a higher mean overall score on the issues list (total M- Issues with the highest scores according to HCPs included score 2.3) compared to patients (total M-score 1.8) (Sup- “worries about tumour growth” (M-score 3.4), “stress about plemental Table 2). the diagnosis” (M-score 3.2), “the experience of uncertainty during the course of the disease” (M-score 3.2), “pain” (M- score 3.2), “concerns about the future” (M-score 3.0), “stress 3.6. EORTC QLQ-C30: Dutch vs. British Participating around check-ups during the follow-up” (M-score 3.0), “fear Patients. Overall, the mean summary score for the EORTC of recurrence after treatment” (M-score 3.0), “fear of tumour QLQ-C30 for all DTF patients together was 78.1, with a mean growth/tumour growth into adjacent tissues or organs” (M- global health score of 68.7 (Table 3). Statistically signiﬁcant score 2.9), and “the feeling that patients do not have a clear diﬀerences between scores of British and Dutch patients were Sarcoma 5 Table 1: Clinical characteristics of 29 participating patients. Dutch British Total group patients patients (%) (n �17) (n �12) Sex Male 10 (35%) 5 (29%) 5 (42%) Female 19 (65%) 12 (71%) 7 (59%) Median age in years at the time of questionnaires (IQR) 43 (36–55) 44 (36–55) 41 (32–56) Median age in years at the time of diagnosis (IQR) 38 (30–48) 38 (30–48) 37 (28–50) Tumour localisation Abdominal wall 2 (7%) 2 (12%) 0 (0%) Intra-abdominal 10 (35%) 8 (47%) 2 (17%) Extremity/girdles/chest wall 15 (52%) 6 (35%) 9 (75%) Head/neck/intrathoracic 1 (3%) 1 (6%) 0 (0%) Missing value 1 (3%) 0 (0%) 1 (6%) Recurrent disease Yes 6 (21%) 2 (12%) 4 (33%) No 21 (72%) 15 (88% 6 (50%) Missing value 2 (7%) 0 (0%) 2 (17%) Received treatments (some patients gave multiple Wait and see 21 12 9 answers) Surgery 14 8 6 Radiotherapy 4 1 3 Chemotherapy 5 1 4 Nonsteroidal anti-inﬂammatory 8 1 7 drugs Hormonal treatment 7 2 5 Pain management 9 0 9 Physiotherapy 7 3 4 Occupational therapy 2 1 1 Currently receiving any active form of treatment Yes 9 (31%) 0 (0%) 9 (75%) No 19 (66%) 17 (100%) 2 (17%) Missing value 1 (3%) 0 (0%) 1 (8%) Comorbidity (some patients gave multiple answers) No 11 6 5 Arthritis or long-term joint problem 3 2 1 Asthma or long-term chest problem 4 2 2 Diabetes 1 1 0 High blood pressure 1 0 1 Kidney or liver disease 1 1 0 Long-term back problem 6 3 3 Long-term mental health problem 2 2 0 Long-term neurological problem 1 1 0 Physical disability 2 1 1 Others 3 2 1 Missing value 2 2 0 a b c Percentages may not add up to 100% due to rounding up of decimals. Answered by n �21 participating patients. Answered by n �29 participating patients. Including digestive problems, coeliac disease lactose intolerance, and iron deﬁciency. found for “global health,” “insomnia,” for the symptom scales global health and the summary score, respectively. British “pain” and “fatigue,” and for the following functioning scales patients (n �8) had a score of 59.4 for global health and a “cognitive functioning,” “emotional functioning,” “social summary score of 68.2, whereas scores for the matched British functioning,” and “role functioning” (Table 3). population were 60.2 and 76.7 for global health and the summary score, respectively (Table 3) [16]. Dutch partici- pating patients scored lower on all functioning scales com- 3.7. EORTC QLQ-C30: Participating Patients versus the pared to the general Dutch population, although only the Matched General Population. After 1:10 nearest-neighbour physical functioning score (p � 0.019) and the role func- matching based on nationality, sex, and age, data of 170 tioning score (p � 0.021) showed a statistically signiﬁcant people from the Dutch general population and data of 80 diﬀerence (Table 3). No statistically signiﬁcant diﬀerences people from the British general population were selected to were found comparing EORTC QLQ-C30 scores between the compare scores between DTF patients and the general British patients and the British general population. population. Four British patients were excluded from this analysis due to missing data regarding their age at the time of 4. Discussion questionnaire completion. Dutch patients had a score of 77 for global health and a summary score of 87.2, whereas scores 'e purpose of this study was to identify the most important for the matched Dutch population were 78.7 and 89.8 for HRQoL issues for patients with sporadic DTF and rank them 6 Sarcoma Table 2: Top 10 most important issues according to the number of participating patients (n). n Prevalence ratio (%) Participating patients (total n �16) Worries about tumour growth 10 62.5 Fear of the tumour growth and/or tumour growing into adjacent tissues or organs 9 56.3 Feeling that there is something in your body that does not belong there 7 43.8 Stress around check-ups during the follow-up 6 37.5 Pain 6 37.5 Reaching a deﬁnite diagnosis is time consuming 5 31.3 Not being able to sleep because of pain 5 31.3 Feeling frustrated about the “benign” diagnosis with malignant features 5 31.3 Desmoid-type ﬁbromatosis is unknown among most doctors 5 31.3 Healthcare providers (total n �31) Worries about tumour growth 17 54.9 Experience of uncertainty during the course of disease 12 38.7 Pain 11 35.5 Lack of optimal treatment options and/or uncertainty about preferred treatment 10 32.3 Concerns about the future 10 32.3 n �13 participating patients failed to provide a top 10. 'e cutoﬀ value for inclusion in the DTF-speciﬁc HRQoL questionnaire is a prevalence ratio of>30%. Table 3: Results of the EORTC QLQ-C30 questionnaire (version 3.0) of patients and the general population. British Dutch Dutch general British general Total mean participating participating population, population, p value (SD) patients patients, n �12 patients, n �17 n �170 mean n �80 mean mean (SD) mean (SD) (SD) (SD) Dyspnoea 10.3 (23.7) 8.0 (15.1) 11.8 (28.7) 0.845 8.2 (19.1) 18.7 (11.8) Insomnia 31 (38.8) 55.6 (38.4) 13.7 (29.0) 0.004 20.8 (25.1) 37.9 (39.6) Appetite loss 14.9 (26.1) 22.2 (21.7) 9.8 (28.3) 0.073 2.9 (11.9) 16.2 (24.8) Constipation 16.7 (32.1) 21.2 (37.3) 13.7 (29.0) 0.781 4.7 (13.7) 14.6 (30.9) Diarrhoea 17.2 (30.4) 27.8 (39.8) 9.8 (19.6) 0.325 7.3 (17.9) 14.2 (45.2) Financial diﬃculties 11.5 (24.0) 22.2 (29.6) 3.9 (16.2) 0.059 5.7 (18.9) 23.3 (34.5) Nausea/vomiting 7.5 (17.6) 13.9 (24.4) 2.9 (8.8) 0.180 4.7 (13.7) 14.6 (28.8) Pain 33.9 (36.0) 58.3 (37.3) 16.7 (23.6) 0.004 16.2 (21.9) 29.4 (40.3) Fatigue 31 (32.9) 49.1 (29.0) 18.3 (29.9) 0.004 22.5 (22.4) 33.9 (32.2) Cognitive functioning 79.9 (30.3) 65.3 (32.1) 90.2 (25.0) 0.030 91.7 (15.7) 76.7 (29.5) Emotional functioning 73.6 (32.4) 59.0 (33.6) 83.8 (28.2) 0.021 84.3 (18.9) 67.3 (36.7) Social functioning 77.6 (29.6) 58.3 (33) 91.2 (17.8) 0.001 94.2 (14.9) 75.4 (38.8) Physical functioning 75.2 (27.9) 67.8 (32.5) 80.3 (23.9) 0.394 92.5 (13.1) 80.2 (33.3) Role functioning 71.8 (32.8) 52.8 (40.1) 85.3 (17.6) 0.027 91.8 (19.5) 76.5 (38.8) Global health status 68.7 (27.7) 56.9 (29.5) 77.0 (23.9) 0.043 78.7 (18.2) 60.2 (34.6) Summary score 78.1 63.5 87.2 89.8 76.7 Data missing from 1 British patient; statistically signiﬁcant diﬀerence. Mean scores with standard deviation (SD) are displayed for all scales of the EORTC QLQ-C30. 'e p value represents the comparison of the scores of the British participating patients versus the scores of the Dutch participating patients. Two- sided p<0.05 was considered statistically signiﬁcant. according to relevance. 'e most highly ranked HRQoL such as pain, fatigue, and loss of muscle strength also re- issues by patients with DTF were related to the unpredictable ceived high priority scores of 2.4, 2.3, and 2.3, respectively. disease trajectory of DTF. Additionally, issues regarding the Although these items are covered by the EORTC QLQ-C30 rarity, aggressiveness, and the benign classiﬁcation of DTF questionnaire, the results of this study highlight the im- received high scores. From the patient perspective, this portance of physical symptoms, caused by the tumour or as a benign classiﬁcation was seen as misleading, as DTF can side eﬀect of treatment, and their impact on HRQoL. Pa- display aggressive growth. In terms of the healthcare system, tients identiﬁed several important issues that were not the benign disease classiﬁcation, not being cancer, can have covered by other questionnaires. 'ese could be considered in the development of a future DTF-speciﬁc HRQoL tool. both pros and cons as it can have consequences for insur- ances and covering of expenses, depending on the country of In a rare and heterogeneous disease, such as DTF, residence. As the aforementioned items are not included in measuring the impact of the disease on patients can be the EORTC QLQ-C30 questionnaire, a tailored DTF challenging. 'is can be due to the variable disease pre- HRQoL tool could capture these issues. Physical symptoms sentation, course, and response to treatment and due to the Sarcoma 7 and lower scores on functioning scales (indicating worse knowledge gap of the natural history of the disease [20]. Moreover, the limited number of responses challenges re- functioning) comparing the data from the general Dutch and British population. Data from 2017 of 'e Organisation for search in this ﬁeld. Our cohort may not be representative of the entire DTF population as the majority of patients in this Economic Co-operation and Development show similar cohort had an intra-abdominal tumour and many patients results with lower scores (indicating a lower well-being) of received one or multiple “active” forms of treatment. British participants compared to Dutch participants on In addition to physical, emotional, and psychological several measures of well-being (e.g., housing, income, ed- problems, patients with DTF might also experience social ucation, and health and life satisfaction) [22]. 'is suggests isolation due to lack of peers with the same condition [20]. that although our data might show diﬀerences between both countries of “impact of disease” on HRQoL, baseline scores 'is was reﬂected in the current study by a relatively high score for the issue “not knowing peers with the same dis- in the normal population diﬀer and that the experience of HRQoL issues depends on where you live [16, 22]. ease.” Furthermore, lack of information was identiﬁed as a relevant topic as the following issues: “DTF is unknown Comparisons between patients and a matched cohort of the general population based on nationality, sex, and age did among most doctors” and “lack of information received about DTF” received M-scores of 2.6 and 1.8, respectively. not yield signiﬁcant results, except for “physical function- HCPs may treat a limited number of patients with this ing” and “role functioning” comparing the Dutch patients rare disease; therefore, patients may receive an incorrect with the Dutch general population. Additionally, we com- diagnosis or delay in diagnosis due to lack of experience in pared the scores of HCPs and participating patients. An recognizing and treating the disease [20]. 'e comparison in important ﬁnding of this study was the clear overlap of issues relevance scores between patients and HCPs shows that that were important to patients and HCPs. 'e HCPs rated various issues higher than patients particularly with regard HCPs scored signiﬁcantly higher on a large number of is- sues, suggesting that they recognize and acknowledge to pain, stress about the diagnosis, and concerns about the future. problems faced by this patient group. 'e issue “reaching a deﬁnite diagnosis is time consuming” received an M-score of We acknowledge that this study has several limitations. 'e small sample size is explained by the rarity of DTF. A 2.3, showing that this is a relevant problem for this patient group. Whilst the future DTF-speciﬁc HRQoL tool will be larger cohort is needed to test the psychometric aspects of a available upon diagnosis, it is important for HCPs to con- DTF-speciﬁc HRQoL tool in future studies. 'e response sider that patients may have encountered diﬃculties rate was lower than we had hoped for, but similar response reaching the correct diagnosis and so provision of clear rates have been published in studies describing more information and support at this time is essential. Accessing common diseases such as cancer [23]. In the current study, specialists with knowledge of DTF can be challenging, as the relatively low response rate may have been due to the length of the questionnaire, the single-centre setup (one they may be located in regional specialist centres. 'is can result in patients receiving multiple treatment recommen- centre in each country), the timing of sending out the questionnaire (midsummer), and/or the overall reluctance dations before seeing a specialist. Financial consequences, due to insurance problems, the to participate in a survey study. Furthermore, many patients need to take time oﬀ work or increasing traveling costs can also need to complete questionnaires as part of their regular also aﬀect HRQoL, although the issues regarding these healthcare; therefore, patients might be less willing to subjects all received relatively low scores in the current study complete questionnaires for research purposes. Sending out [21]. Social problems, such as the burden of having a rare a reminder to patients would have been a valid option to disease on family and carers, as well as having this diagnosis increase the response rate. Selection bias may have led to an at a young age, can also have a negative impact on HRQoL overestimation of HRQoL problems in our cohort. As the [20, 21]. primary aim was to identify the most relevant issues in this patient group, the eﬀect of this overestimation is less rele- 'is unique study identiﬁed important issues for DTF patients and compared the views of British and Dutch pa- vant. A population-based cohort is required to determine the true prevalence of issues and perhaps a more representative tients. Most issues were scored higher by British patients compared to Dutch patients (indicating a higher relevance result. Lastly, interpretation of the questions is inﬂuenced by for the speciﬁc issue). 'is phenomenon was also seen the current health situation of each patient. We tried to comparing EORTC QLQ-C30 scores, as British patients eliminate such inﬂuencing factors by excluding patients with scored statistically signiﬁcantly lower (indicating worse a diagnosis of cancer and FAP-associated DTF. However, functioning) on four out of ﬁve function scales, and for the patients HRQoL might also be inﬂuenced by disease stage, symptom scales insomnia, pain, and fatigue. Although both tumour location, and treatments and by other comorbidities and personal circumstances. 'is impact on HRQoL issues participating centres are tertiary centres visited by patients with more complex or advanced disease, the catchment area could be evaluated in a future population-based cohort study and stresses the need for validation of our ﬁndings in a large, of the Royal Marsden Hospital (London, UK) is larger than that of the Erasmus MC (Rotterdam, NL) possibly creating international DTF cohort to evaluate the prevalence of HRQoL issues. selection bias during this study. Norm data obtained by the EORTC of the general Dutch and British population showed Today, solely one DTF-speciﬁc questionnaire, the a comparable trend with higher scores on symptom scales Gounder/DTRF Desmoid Symptom/Impact Scale, is avail- and single items scales (indicating greater symptom burden) able and currently mainly used in the setting of clinical trials 8 Sarcoma [24–26]. 'e ﬁndings of our study will be used for the acknowledge the funding and support from Stichting development of a DTF-speciﬁc tool, according to the Coolsingel, Rotterdam, the Netherlands (grant no. 566), the EORTC guidelines, which can be used, accompanied by the NIHR Biomedical Research Centre at 'e Royal Marsden EORTC QLQ-C30 HRQoL instrument and will be useful for and the Institute of Cancer Research, London (NIHR RM/ observational studies, clinical trials, and clinical care. ICR BRC), and the National Institute for Health Research Implementation of this tool and action on abnormal ﬁnd- Clinical Research Network (NIHR CRN). Dr. Olga Husson ings, concerns, or poor experiences of patients might im- is supported by a Social Psychology Fellowship from the prove satisfaction with healthcare, symptom management, Dutch Cancer Society (#KUN2015-7527). and HRQoL [27]. Healthcare providers may beneﬁt from being able to anticipate and identify problems earlier, Supplementary Materials thereby improving work eﬃciency and promoting patient- centred care through shared decision-making [28–30]. In Supplemental Figure 1: diﬀerences in score of more than 1 order for a tailored HRQoL tool to work in clinical practice, point between Dutch and British patients. Supplemental this tool should add value to the clinical workﬂow without Table 1: sociodemographic characteristics of 29 participating disrupting it [31]. Our results will be used in the develop- patients. Supplemental Table 2: mean M-scores per issue ment of an international, multicentre, population-based ranked according to their relevance. Supplemental Table 3: study in line with the EORTC guidelines for developing a missing issues and quotes from patients. Supplemental questionnaire [14]. 'is study includes pretesting and Table 4: general remarks and quotes from patients. (Sup- content validation of a DTF-speciﬁc questionnaire. 'is plementary Materials) questionnaire will assess the prevalence of HRQoL issues and will identify risk factors for the development of HRQoL References issues patients experience. Patients will receive an invitation to participate in an online survey and one reminder for [1] C. D. M. Fletcher, K. Krishnan Unni, and F. Mertens, WHO completing the questionnaire. 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[25] SpringWorks 'erapeutics, Inc., NCT03785964-Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (DeFi), https://clinicaltrials.gov/ct2/show/ NCT03785964?term�03785964&draw�2&rank�1. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sarcoma Hindawi Publishing Corporation http://www.deepdyve.com/lp/hindawi-publishing-corporation/assessing-the-desmoid-type-fibromatosis-patients-voice-comparison-of-5cWQlD3qhG

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Publisher: Hindawi Publishing Corporation
Copyright: Copyright © 2020 Milea J. M. Timbergen et al. This 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.
ISSN: 1357-714X
eISSN: 1369-1643
DOI: 10.1155/2020/2141939
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Abstract

Hindawi Sarcoma Volume 2020, Article ID 2141939, 9 pages https://doi.org/10.1155/2020/2141939 Research Article Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries 1,2 3,4 1 Milea J. M. Timbergen , Winette T. A. van der Graaf, Dirk J. Gru¨nhagen, 5,6 2 5 5 1 Eugenie Younger, Stefan Sleijfer, Alison Dunlop, Lucy Dean, Cornelis Verhoef, 7,8,9 3,5,6,7 Lonneke V. van de Poll-Franse, and Olga Husson Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands Department of Medical Oncology, !e Netherlands Cancer Institute, Amsterdam, Netherlands Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands Sarcoma Unit, Royal Marsden NHS Foundation Trust, London, UK Division of Clinical Studies, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK Division of Psychosocial Research and Epidemiology, !e Netherlands Cancer Institute, Amsterdam, Netherlands Department of Medical and Clinical Psychology, Tilburg University, Netherlands Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, Netherlands Correspondence should be addressed to Milea J. M. Timbergen; m.timbergen@erasmusmc.nl Received 4 May 2020; Revised 27 June 2020; Accepted 29 June 2020; Published 26 July 2020 Academic Editor: Ajay Puri Copyright © 2020 Milea J. M. Timbergen 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. Purpose. Desmoid-type ﬁbromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of deﬁnitive treatments, and the chronic character of the disease can signiﬁcantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a speciﬁc HRQoL questionnaire for this patient group. Methods. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. Results. 'e most highly ranked issues by patients (n �29) were issues concerning “tumour growth,” “feeling that there is something in the body that does not belong there,” and “fear of tumour growth into adjacent tissues or organs” with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1–4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n �31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). Conclusion. 'is study identiﬁed the most relevant issues for DTF patients, which should be included in a DTF-speciﬁc HRQoL questionnaire. Additionally, we identiﬁed diﬀerences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to conﬁrm these ﬁndings and to devise a comprehensive and speciﬁc HRQoL questionnaire for DTF patients. Sporadic DTF arises in musculoaponeurotic structures with 1. Introduction the most common sites being the abdominal wall and the Sporadic desmoid-type ﬁbromatosis (DTF) is a rare, bor- extremities [4]. Symptoms vary, depending on tumour site, derline tumour of the soft tissues [1–3]. Most patients are size, and inﬁltration of adjacent structures, resulting in pain females,agedbetween 20and40 years atprimarydiagnosis [3]. and/or functional impairment. DTF does not metastasize, 2 Sarcoma rarely has fatal outcomes, often displays long periods of identiﬁed in the Dutch group. Next, issues were grouped spontaneous stabilisation, and can undergo spontaneous re- into categories and duplicate issues covering the same topics gression [5]. Surgical resection, radiotherapy, and non- were removed. A total of 124 issues were converted into a cytotoxic and cytotoxic systemic therapies may be considered provisional list of issues. All issues were reviewed by two in patients with symptomatic disease, but unfortunately, these authors (MT and OH). All issues were translated by native “traditional” treatment options do not guarantee tumour re- English and Dutch speakers. duction and/or clinical response [6]. Local recurrence after surgery remains high [7, 8], leading to a reduction in surgical treatments for DTF over recent decades [3, 4]. Additionally, 2.2. Patient Selection. Patients with DTF were approached for participation by their treating physician. Inclusion cri- “active” forms of treatment can be debilitating, causing greater morbidity than the tumour itself. For these reasons, active teria were histologically proven DTF, age ≥18 years, Dutch or English language skills, and a “recent” visit (<2 years) to surveillance is now recommended as a ﬁrst-line management for most patients with DTF [6, 9].'erefore, DTF has obtained the hospital. Exclusion criteria were participation in one of the previous focus groups or patient interviews and patients a “chronic” status and its impact on patients should be with a diagnosis of cancer or familial adenomatous polyposis evaluated accordingly. Health-related quality of life (HRQoL) provides infor- (FAP). Patients received an information letter which explained study objectives. Baseline characteristics and mation beyond traditional measures of eﬃcacy in oncology such as overall survival and is increasingly used as an details about the individual disease trajectory of participants were obtained. Patients were only invited to participate once endpoint in clinical trials [10, 11]. We previously performed a systematic literature review to evaluate which HRQoL and did not have to provide a reason if they declined. No reminders were sent. All data from patients was collected measures were used in research to assess HRQoL in DTF [12]. Generic HRQoL measures (e.g., the cancer-speciﬁc core and processed anonymously. questionnaire from European Organisation for Research and Treatment of Cancer; the EORTC Quality of Life Core 2.3. Selection of Healthcare Providers. To examine whether Questionnaire (EORTC QLQ-C30)) may not consider dis- HCPs with expertise and experience in sarcomas and DTF ease-speciﬁc issues in DTF patients. Site-speciﬁc tools (e.g., have the same perspectives as patients with DTF about key Toronto Extremity Salvage Score) may not be relevant to HRQoL issues, an e-survey of the same 124 issues was certain groups (e.g., those with abdominal wall or head and created using LimeSurvey Servicebedrijf© software. 'e neck tumours). issue list was available in two languages (Dutch and English), At present, there is no validated DTF-speciﬁc HRQoL and issues were presented in a random order. In the tool, and this was illustrated by a systematic literature review Netherlands, HCPs from the multidisciplinary team (e.g., published by our group [12, 13]. In order to gain greater surgeons, oncologists, radiologists, radiotherapists, sarcoma insight into the issues that patients with DTF experience in clinical nurse specialists, and physiotherapists) were iden- their daily lives, and to evaluate their experiences of tiﬁed using the website Orphanet, which provides infor- healthcare including the supportive care system, we previ- ously organised focus groups and semistructured interviews, mation on centres of expertise dedicated to the medical management for rare diseases (https://www.orpha.net/ in the United Kingdom (UK) and in the Netherlands (NL) consor/cgi-bin/Clinics_Search.php?lng�EN). In the UK, [12, 13]. 'ese studies identiﬁed issues covering various HCPs of the aforementioned disciplines were identiﬁed domains including the diagnostic pathway, the treatment using the sarcoma network group of the Royal Marsden pathway, daily limitations (e.g., physical and psychological Hospital, London, UK. Every HCP received an invitation symptoms), and experiences with the current healthcare email with a token and link to the e-survey. A reminder was system. sent after one week if the HCP had not responded. 'e main goal of this study was to determine the relative importance of each issue and receiving feedback on the appropriateness of content and breadth of coverage. In the 2.4. Sociodemographic and Clinical Characteristics. Age at present study, we used the previously identiﬁed issues to (1) the time of diagnosis was either stated by the patient or identify the most relevant issues to patients with DTF in two calculated using the date of birth and date of the ﬁrst pa- healthcare settings (UK and NL) and to (2) identify dif- thology report. Age at the time of questionnaire completion ferences in scores between both countries. was either stated by the patient or calculated using the date of informed consent and the date of birth. Education levels 2. Materials and Methods were categorized into “high” (PhD, university, and higher education postgraduate/undergraduate degree), “interme- 2.1. Identiﬁcation of Issues. 'e EORTC Quality of Life diate” (professional qualiﬁcation, vocational work, work- Group methodology for developing a questionnaire was related qualiﬁcation, general secondary education, and used for the selection of relevant issues based on previous further/intermediate education), and “low” (primary edu- focus groups and patients interviews [14]. Issues that had cation (with a higher, but not completed education) and previously been identiﬁed to be of concern to DTF patients secondary education). Continuous variables were presented were listed per country (UK and NL). A total of 188 issues as a mean with a standard deviation (SD) or as a median with were identiﬁed in the UK group and 110 issues were Sarcoma 3 age or sex) were excluded from the analysis. Diﬀerences in an interquartile range (IQR). Categorical variables were presented as number (n) using frequencies and percentages. priority scores (Dutch versus British participating patients and HCPs versus participating patients) and diﬀerences in scores of the EORTC QLQ-C30 scales between groups 2.5. Presentation of Issues to Patients and Healthcare (Dutch versus British participating patients and Dutch and Providers. A total of 124 issues were presented to patients British participating patients versus the Dutch and British and healthcare providers (HCPs) in a random order general population) were tested for their signiﬁcance using (Supplemental Table 1). Patients and HCPs scored 124 issues the Mann–Whitney U test. SPSS Statistics (version 24) was by relevance on a Likert scale from 1 to 4 ((1) not at all, (2) a used for the Mann–Whitney U tests (IBM, Armonk, New little, (3) quite a bit, and (4) very much) and ranked the top York, USA). Two-sided p<0.05 was considered statistically ten most important issues. 'e frequency that each issue signiﬁcant. appeared in the top ten most important issues was converted into the mean priority score (M-score) per issue. 'e fre- 3. Results quency of the top ten priority score of each issue was cal- culated and ranked in overall priority score. Where 3.1. PatientCohort. Forty-one patientsfrom the ErasmusMC, questions were left blank by the participant, they were coded Rotterdam, the Netherlands, and 32 patients from the Royal as a “missing value” and not incorporated in the total score. Marsden Hospital, London, UK, were approached during July Space for general remarks was available at the end of the and August 2018. Out of 73 patients, 29 patients (total re- questionnaire. sponse rate of 39.7%) gave written informed consent (Fig- ure 1). 'e cohort comprised of 10 males and 19 females with DTF most commonly localized in the extremities, ﬂank, and 2.6. EORTC QLQ-C30 Questionnaire. In addition to the chest wall (n �15, 52%). Nine participants had received active issue list, patients were asked to ﬁll out the 30-item EORTC treatment at the time of the questionnaire. 'e median, self- QLQ-C30 questionnaire (version 3) to assess HRQoL [15]. reported age at diagnosis was 38 years (IQR 30–48) (Table 1). Norm data were obtained from the EORTC, which recently Sociodemographic characteristics are summarized in Sup- collected data from the general population in Europe and plemental Table 1. All participants completed the issue list, and North America [16]. Only data from the general population sixteen participants ranked their top 10 most relevant issues. in the Netherlands and the UK were used for the current study. 'e EORTC QLQ-C30 questionnaire contains ﬁve functional scales (physical, role, cognitive, emotional, and 3.2. Ranking of Priority of the Issues. Ranking of HRQoL social functioning), a global health status scale, three issues revealed that 13 out of 124 issues (10.5%) were chosen symptom scales (fatigue, nausea and vomiting, and pain), to be the most relevant (prevalence ratio of >30%) (Table 2). and six single items (appetite loss, diarrhoea, dyspnoea, Patients considered the following issues as relevant and constipation, insomnia, and ﬁnancial diﬃculties). 'e missing on the current issue list: “problems with healthcare questionnaire has a 1-week time frame and uses a four-point insurances,” “coverage of costs related to the disease such as response format (“not at all,” “a little,” “quite a bit,” and traveling costs,” “lack of adequate online information,” “lack “very much”), with the exception of the global health status of knowledge about treatment options outside the region or scale, which has a seven-point response format. 'e scores country,” “lack of information about pain management and were calculated using linear transformation to a score be- referral to pain professionals,” and “lack of advice regarding tween 0 and 100. For the functional scales and the global dietary restrictions or playing sports.” A list of the missing health status, a high score represents a high (healthy) level of items, general remarks, and quotes is provided in Supple- functioning. A high score for the symptom scales represents mental Tables 3 and 4. a high level of symptoms (greater symptom burden) [17]. 'e EORTC QLQ-C30 summary score was calculated using the mean scores of the function scales and the reversed mean 3.3. British versus Dutch Patients. Overall, British patients scores of the symptom scales and single items (ﬁnancial gave higher scores for each issue compared to Dutch patients impact and global health status excluded) and is summarized (M-score 2.2 (UK) vs. M-score 1.5 (NL)) (Supplemental as the mean of the combined 13 QLQ-C30 scale scores. A Table 2). Diﬀerences in score of more than 1 point between higher summary score represented a better outcome [18, 19]. Dutch and British patients are displayed in Supplemental 'e summary score was only calculated when all of the Figure 1. Additionally, priority scores of Dutch and British required 13 scale and item scores were available. Data HCPs and scores of participating patients and HCPs from analysis and handling of missing items were done according the Netherlands and the UK were compared (Supplemental to the scoring manual of the EORTC [17]. Table 2). 'e total cohort of patients was too small to identify any diﬀerences between subgroups (e.g., initial treatment type, tumour location, and age at diagnosis). 2.7. Statistical Analysis. Patients were matched, using a 1:10 nearest-neighbour match method, with the general pop- ulation based on nationality, age, and sex using RStudio 3.4. Healthcare Providers. In the Netherlands, HCPs were (RStudio, version 1.0.153, Boston, MA, package MatchIt). invited to six sarcoma centres. All HCPs from the UK were Patients with missing values (lacking information regarding employees at the Royal Marsden Hospital, London. Twenty- 4 Sarcoma Patients Dutch patients British patients No response No response invited to invited to n = 24 n = 20 participate participate n = 41 n = 32 Completion of Completion of Response rate Response rate questionnaires questionnaires 41.5% 37.5% n = 17 n = 12 Completed questionnaires n = 29 Healthcare providers (HCPs) Dutch HCPs British HCPs No response No response invited to invited to n = 23 n = 12 participate participate n = 44 n = 22 Completion of Completion of Response rate Response rate questionnaires questionnaires 47.8% 45.5% n = 21 n = 10 Completed questionnaires n = 31 Figure 1: Flow diagram of participating patients and healthcare providers’ responses to this survey. prognosis” (M-score 2.9). Overall, HCPs from the UK gave one Dutch and ten British HCPs responded. Professional backgrounds included surgical oncologist (n �12), medical higher scores, compared to Dutch HCPs with M-scores of 2.8 oncologist (n �6), radiation oncologist (n �5), specialized and 2.0, respectively (Supplemental Table 2). sarcoma nurse (n �5), and other professions including a radiologist, physiotherapist, and pain specialist (all n �1). 3.5. Participating Patients versus Healthcare Providers. Seventeen professionals had more than 10 years of experi- 'ere was considerable overlap between the highest ranked ence, three had 6–10 years of experience, and eleven had 5 or issues according to patients and HCPs, particularly re- less years of experience working with desmoid patients. garding the unpredictable growth pattern of DTF tumours Frequency of contact with DTF patients varied between once (Supplemental Table 1). HCPs scored signiﬁcantly higher a week (n �9, 29%) to rarely (less than once every 3 months) (p<0.05) on 77 out of a total of 77 of 124 issues. HCPs also (n �1, 3%). gave a higher mean overall score on the issues list (total M- Issues with the highest scores according to HCPs included score 2.3) compared to patients (total M-score 1.8) (Sup- “worries about tumour growth” (M-score 3.4), “stress about plemental Table 2). the diagnosis” (M-score 3.2), “the experience of uncertainty during the course of the disease” (M-score 3.2), “pain” (M- score 3.2), “concerns about the future” (M-score 3.0), “stress 3.6. EORTC QLQ-C30: Dutch vs. British Participating around check-ups during the follow-up” (M-score 3.0), “fear Patients. Overall, the mean summary score for the EORTC of recurrence after treatment” (M-score 3.0), “fear of tumour QLQ-C30 for all DTF patients together was 78.1, with a mean growth/tumour growth into adjacent tissues or organs” (M- global health score of 68.7 (Table 3). Statistically signiﬁcant score 2.9), and “the feeling that patients do not have a clear diﬀerences between scores of British and Dutch patients were Sarcoma 5 Table 1: Clinical characteristics of 29 participating patients. Dutch British Total group patients patients (%) (n �17) (n �12) Sex Male 10 (35%) 5 (29%) 5 (42%) Female 19 (65%) 12 (71%) 7 (59%) Median age in years at the time of questionnaires (IQR) 43 (36–55) 44 (36–55) 41 (32–56) Median age in years at the time of diagnosis (IQR) 38 (30–48) 38 (30–48) 37 (28–50) Tumour localisation Abdominal wall 2 (7%) 2 (12%) 0 (0%) Intra-abdominal 10 (35%) 8 (47%) 2 (17%) Extremity/girdles/chest wall 15 (52%) 6 (35%) 9 (75%) Head/neck/intrathoracic 1 (3%) 1 (6%) 0 (0%) Missing value 1 (3%) 0 (0%) 1 (6%) Recurrent disease Yes 6 (21%) 2 (12%) 4 (33%) No 21 (72%) 15 (88% 6 (50%) Missing value 2 (7%) 0 (0%) 2 (17%) Received treatments (some patients gave multiple Wait and see 21 12 9 answers) Surgery 14 8 6 Radiotherapy 4 1 3 Chemotherapy 5 1 4 Nonsteroidal anti-inﬂammatory 8 1 7 drugs Hormonal treatment 7 2 5 Pain management 9 0 9 Physiotherapy 7 3 4 Occupational therapy 2 1 1 Currently receiving any active form of treatment Yes 9 (31%) 0 (0%) 9 (75%) No 19 (66%) 17 (100%) 2 (17%) Missing value 1 (3%) 0 (0%) 1 (8%) Comorbidity (some patients gave multiple answers) No 11 6 5 Arthritis or long-term joint problem 3 2 1 Asthma or long-term chest problem 4 2 2 Diabetes 1 1 0 High blood pressure 1 0 1 Kidney or liver disease 1 1 0 Long-term back problem 6 3 3 Long-term mental health problem 2 2 0 Long-term neurological problem 1 1 0 Physical disability 2 1 1 Others 3 2 1 Missing value 2 2 0 a b c Percentages may not add up to 100% due to rounding up of decimals. Answered by n �21 participating patients. Answered by n �29 participating patients. Including digestive problems, coeliac disease lactose intolerance, and iron deﬁciency. found for “global health,” “insomnia,” for the symptom scales global health and the summary score, respectively. British “pain” and “fatigue,” and for the following functioning scales patients (n �8) had a score of 59.4 for global health and a “cognitive functioning,” “emotional functioning,” “social summary score of 68.2, whereas scores for the matched British functioning,” and “role functioning” (Table 3). population were 60.2 and 76.7 for global health and the summary score, respectively (Table 3) [16]. Dutch partici- pating patients scored lower on all functioning scales com- 3.7. EORTC QLQ-C30: Participating Patients versus the pared to the general Dutch population, although only the Matched General Population. After 1:10 nearest-neighbour physical functioning score (p � 0.019) and the role func- matching based on nationality, sex, and age, data of 170 tioning score (p � 0.021) showed a statistically signiﬁcant people from the Dutch general population and data of 80 diﬀerence (Table 3). No statistically signiﬁcant diﬀerences people from the British general population were selected to were found comparing EORTC QLQ-C30 scores between the compare scores between DTF patients and the general British patients and the British general population. population. Four British patients were excluded from this analysis due to missing data regarding their age at the time of 4. Discussion questionnaire completion. Dutch patients had a score of 77 for global health and a summary score of 87.2, whereas scores 'e purpose of this study was to identify the most important for the matched Dutch population were 78.7 and 89.8 for HRQoL issues for patients with sporadic DTF and rank them 6 Sarcoma Table 2: Top 10 most important issues according to the number of participating patients (n). n Prevalence ratio (%) Participating patients (total n �16) Worries about tumour growth 10 62.5 Fear of the tumour growth and/or tumour growing into adjacent tissues or organs 9 56.3 Feeling that there is something in your body that does not belong there 7 43.8 Stress around check-ups during the follow-up 6 37.5 Pain 6 37.5 Reaching a deﬁnite diagnosis is time consuming 5 31.3 Not being able to sleep because of pain 5 31.3 Feeling frustrated about the “benign” diagnosis with malignant features 5 31.3 Desmoid-type ﬁbromatosis is unknown among most doctors 5 31.3 Healthcare providers (total n �31) Worries about tumour growth 17 54.9 Experience of uncertainty during the course of disease 12 38.7 Pain 11 35.5 Lack of optimal treatment options and/or uncertainty about preferred treatment 10 32.3 Concerns about the future 10 32.3 n �13 participating patients failed to provide a top 10. 'e cutoﬀ value for inclusion in the DTF-speciﬁc HRQoL questionnaire is a prevalence ratio of>30%. Table 3: Results of the EORTC QLQ-C30 questionnaire (version 3.0) of patients and the general population. British Dutch Dutch general British general Total mean participating participating population, population, p value (SD) patients patients, n �12 patients, n �17 n �170 mean n �80 mean mean (SD) mean (SD) (SD) (SD) Dyspnoea 10.3 (23.7) 8.0 (15.1) 11.8 (28.7) 0.845 8.2 (19.1) 18.7 (11.8) Insomnia 31 (38.8) 55.6 (38.4) 13.7 (29.0) 0.004 20.8 (25.1) 37.9 (39.6) Appetite loss 14.9 (26.1) 22.2 (21.7) 9.8 (28.3) 0.073 2.9 (11.9) 16.2 (24.8) Constipation 16.7 (32.1) 21.2 (37.3) 13.7 (29.0) 0.781 4.7 (13.7) 14.6 (30.9) Diarrhoea 17.2 (30.4) 27.8 (39.8) 9.8 (19.6) 0.325 7.3 (17.9) 14.2 (45.2) Financial diﬃculties 11.5 (24.0) 22.2 (29.6) 3.9 (16.2) 0.059 5.7 (18.9) 23.3 (34.5) Nausea/vomiting 7.5 (17.6) 13.9 (24.4) 2.9 (8.8) 0.180 4.7 (13.7) 14.6 (28.8) Pain 33.9 (36.0) 58.3 (37.3) 16.7 (23.6) 0.004 16.2 (21.9) 29.4 (40.3) Fatigue 31 (32.9) 49.1 (29.0) 18.3 (29.9) 0.004 22.5 (22.4) 33.9 (32.2) Cognitive functioning 79.9 (30.3) 65.3 (32.1) 90.2 (25.0) 0.030 91.7 (15.7) 76.7 (29.5) Emotional functioning 73.6 (32.4) 59.0 (33.6) 83.8 (28.2) 0.021 84.3 (18.9) 67.3 (36.7) Social functioning 77.6 (29.6) 58.3 (33) 91.2 (17.8) 0.001 94.2 (14.9) 75.4 (38.8) Physical functioning 75.2 (27.9) 67.8 (32.5) 80.3 (23.9) 0.394 92.5 (13.1) 80.2 (33.3) Role functioning 71.8 (32.8) 52.8 (40.1) 85.3 (17.6) 0.027 91.8 (19.5) 76.5 (38.8) Global health status 68.7 (27.7) 56.9 (29.5) 77.0 (23.9) 0.043 78.7 (18.2) 60.2 (34.6) Summary score 78.1 63.5 87.2 89.8 76.7 Data missing from 1 British patient; statistically signiﬁcant diﬀerence. Mean scores with standard deviation (SD) are displayed for all scales of the EORTC QLQ-C30. 'e p value represents the comparison of the scores of the British participating patients versus the scores of the Dutch participating patients. Two- sided p<0.05 was considered statistically signiﬁcant. according to relevance. 'e most highly ranked HRQoL such as pain, fatigue, and loss of muscle strength also re- issues by patients with DTF were related to the unpredictable ceived high priority scores of 2.4, 2.3, and 2.3, respectively. disease trajectory of DTF. Additionally, issues regarding the Although these items are covered by the EORTC QLQ-C30 rarity, aggressiveness, and the benign classiﬁcation of DTF questionnaire, the results of this study highlight the im- received high scores. From the patient perspective, this portance of physical symptoms, caused by the tumour or as a benign classiﬁcation was seen as misleading, as DTF can side eﬀect of treatment, and their impact on HRQoL. Pa- display aggressive growth. In terms of the healthcare system, tients identiﬁed several important issues that were not the benign disease classiﬁcation, not being cancer, can have covered by other questionnaires. 'ese could be considered in the development of a future DTF-speciﬁc HRQoL tool. both pros and cons as it can have consequences for insur- ances and covering of expenses, depending on the country of In a rare and heterogeneous disease, such as DTF, residence. As the aforementioned items are not included in measuring the impact of the disease on patients can be the EORTC QLQ-C30 questionnaire, a tailored DTF challenging. 'is can be due to the variable disease pre- HRQoL tool could capture these issues. Physical symptoms sentation, course, and response to treatment and due to the Sarcoma 7 and lower scores on functioning scales (indicating worse knowledge gap of the natural history of the disease [20]. Moreover, the limited number of responses challenges re- functioning) comparing the data from the general Dutch and British population. Data from 2017 of 'e Organisation for search in this ﬁeld. Our cohort may not be representative of the entire DTF population as the majority of patients in this Economic Co-operation and Development show similar cohort had an intra-abdominal tumour and many patients results with lower scores (indicating a lower well-being) of received one or multiple “active” forms of treatment. British participants compared to Dutch participants on In addition to physical, emotional, and psychological several measures of well-being (e.g., housing, income, ed- problems, patients with DTF might also experience social ucation, and health and life satisfaction) [22]. 'is suggests isolation due to lack of peers with the same condition [20]. that although our data might show diﬀerences between both countries of “impact of disease” on HRQoL, baseline scores 'is was reﬂected in the current study by a relatively high score for the issue “not knowing peers with the same dis- in the normal population diﬀer and that the experience of HRQoL issues depends on where you live [16, 22]. ease.” Furthermore, lack of information was identiﬁed as a relevant topic as the following issues: “DTF is unknown Comparisons between patients and a matched cohort of the general population based on nationality, sex, and age did among most doctors” and “lack of information received about DTF” received M-scores of 2.6 and 1.8, respectively. not yield signiﬁcant results, except for “physical function- HCPs may treat a limited number of patients with this ing” and “role functioning” comparing the Dutch patients rare disease; therefore, patients may receive an incorrect with the Dutch general population. Additionally, we com- diagnosis or delay in diagnosis due to lack of experience in pared the scores of HCPs and participating patients. An recognizing and treating the disease [20]. 'e comparison in important ﬁnding of this study was the clear overlap of issues relevance scores between patients and HCPs shows that that were important to patients and HCPs. 'e HCPs rated various issues higher than patients particularly with regard HCPs scored signiﬁcantly higher on a large number of is- sues, suggesting that they recognize and acknowledge to pain, stress about the diagnosis, and concerns about the future. problems faced by this patient group. 'e issue “reaching a deﬁnite diagnosis is time consuming” received an M-score of We acknowledge that this study has several limitations. 'e small sample size is explained by the rarity of DTF. A 2.3, showing that this is a relevant problem for this patient group. Whilst the future DTF-speciﬁc HRQoL tool will be larger cohort is needed to test the psychometric aspects of a available upon diagnosis, it is important for HCPs to con- DTF-speciﬁc HRQoL tool in future studies. 'e response sider that patients may have encountered diﬃculties rate was lower than we had hoped for, but similar response reaching the correct diagnosis and so provision of clear rates have been published in studies describing more information and support at this time is essential. Accessing common diseases such as cancer [23]. In the current study, specialists with knowledge of DTF can be challenging, as the relatively low response rate may have been due to the length of the questionnaire, the single-centre setup (one they may be located in regional specialist centres. 'is can result in patients receiving multiple treatment recommen- centre in each country), the timing of sending out the questionnaire (midsummer), and/or the overall reluctance dations before seeing a specialist. Financial consequences, due to insurance problems, the to participate in a survey study. Furthermore, many patients need to take time oﬀ work or increasing traveling costs can also need to complete questionnaires as part of their regular also aﬀect HRQoL, although the issues regarding these healthcare; therefore, patients might be less willing to subjects all received relatively low scores in the current study complete questionnaires for research purposes. Sending out [21]. Social problems, such as the burden of having a rare a reminder to patients would have been a valid option to disease on family and carers, as well as having this diagnosis increase the response rate. Selection bias may have led to an at a young age, can also have a negative impact on HRQoL overestimation of HRQoL problems in our cohort. As the [20, 21]. primary aim was to identify the most relevant issues in this patient group, the eﬀect of this overestimation is less rele- 'is unique study identiﬁed important issues for DTF patients and compared the views of British and Dutch pa- vant. A population-based cohort is required to determine the true prevalence of issues and perhaps a more representative tients. Most issues were scored higher by British patients compared to Dutch patients (indicating a higher relevance result. Lastly, interpretation of the questions is inﬂuenced by for the speciﬁc issue). 'is phenomenon was also seen the current health situation of each patient. We tried to comparing EORTC QLQ-C30 scores, as British patients eliminate such inﬂuencing factors by excluding patients with scored statistically signiﬁcantly lower (indicating worse a diagnosis of cancer and FAP-associated DTF. However, functioning) on four out of ﬁve function scales, and for the patients HRQoL might also be inﬂuenced by disease stage, symptom scales insomnia, pain, and fatigue. Although both tumour location, and treatments and by other comorbidities and personal circumstances. 'is impact on HRQoL issues participating centres are tertiary centres visited by patients with more complex or advanced disease, the catchment area could be evaluated in a future population-based cohort study and stresses the need for validation of our ﬁndings in a large, of the Royal Marsden Hospital (London, UK) is larger than that of the Erasmus MC (Rotterdam, NL) possibly creating international DTF cohort to evaluate the prevalence of HRQoL issues. selection bias during this study. Norm data obtained by the EORTC of the general Dutch and British population showed Today, solely one DTF-speciﬁc questionnaire, the a comparable trend with higher scores on symptom scales Gounder/DTRF Desmoid Symptom/Impact Scale, is avail- and single items scales (indicating greater symptom burden) able and currently mainly used in the setting of clinical trials 8 Sarcoma [24–26]. 'e ﬁndings of our study will be used for the acknowledge the funding and support from Stichting development of a DTF-speciﬁc tool, according to the Coolsingel, Rotterdam, the Netherlands (grant no. 566), the EORTC guidelines, which can be used, accompanied by the NIHR Biomedical Research Centre at 'e Royal Marsden EORTC QLQ-C30 HRQoL instrument and will be useful for and the Institute of Cancer Research, London (NIHR RM/ observational studies, clinical trials, and clinical care. ICR BRC), and the National Institute for Health Research Implementation of this tool and action on abnormal ﬁnd- Clinical Research Network (NIHR CRN). Dr. Olga Husson ings, concerns, or poor experiences of patients might im- is supported by a Social Psychology Fellowship from the prove satisfaction with healthcare, symptom management, Dutch Cancer Society (#KUN2015-7527). and HRQoL [27]. Healthcare providers may beneﬁt from being able to anticipate and identify problems earlier, Supplementary Materials thereby improving work eﬃciency and promoting patient- centred care through shared decision-making [28–30]. In Supplemental Figure 1: diﬀerences in score of more than 1 order for a tailored HRQoL tool to work in clinical practice, point between Dutch and British patients. Supplemental this tool should add value to the clinical workﬂow without Table 1: sociodemographic characteristics of 29 participating disrupting it [31]. Our results will be used in the develop- patients. Supplemental Table 2: mean M-scores per issue ment of an international, multicentre, population-based ranked according to their relevance. Supplemental Table 3: study in line with the EORTC guidelines for developing a missing issues and quotes from patients. Supplemental questionnaire [14]. 'is study includes pretesting and Table 4: general remarks and quotes from patients. (Sup- content validation of a DTF-speciﬁc questionnaire. 'is plementary Materials) questionnaire will assess the prevalence of HRQoL issues and will identify risk factors for the development of HRQoL References issues patients experience. Patients will receive an invitation to participate in an online survey and one reminder for [1] C. D. M. Fletcher, K. Krishnan Unni, and F. Mertens, WHO completing the questionnaire. 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Journal

Sarcoma – Hindawi Publishing Corporation

Published: Jul 26, 2020

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Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

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Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

Assessing the Desmoid-Type Fibromatosis Patients’ Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries

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