Health-related quality Of Life I n patients with advanced Soft TIssue sarcomas treated with Chemotherapy (The HOLISTIC study): protocol for an international observational cohort study

Eugenie Younger, Robin L Jones, Ingrid M E Desar, Clare Peckitt, Winette T A van der Graaf, Olga Husson, Eugenie Younger, Robin L Jones, Ingrid M E Desar, Clare Peckitt, Winette T A van der Graaf, Olga Husson

Abstract

Introduction: Chemotherapy is the mainstay of treatment for patients with advanced soft tissue sarcomas (STS). Treatment intent is usually palliative, aiming to improve symptoms, stabilise or reduce tumour burden and extend life. Clinical trials have traditionally used radiological response, time to progression and survival as measures of treatment efficacy. Health-related quality of life (HRQoL) is at least equally important or more important than survival for many patients with advanced cancer. Systematically collecting HRQoL data during chemotherapy can provide greater insight into treatment efficacy from the patient perspective.The primary aims of this study are to evaluate HRQoL in patients with advanced STS treated with chemotherapy over time, explore the decision-making process and patient reflection post-treatment.

Methods and analysis: This is an observational, international cohort study for 132 patients aged ≥18 years with advanced STS treated at eight centres (three in the UK, five in the Netherlands). Patients will be recruited prior to starting first-line or third-line chemotherapy and invited to complete questionnaires using the Patient-Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry (PROFILES); an established international registry for collection of cancer patient-reported outcomes. Online (or paper) questionnaires will be completed at baseline, each cycle of chemotherapy and 2-3 monthly during follow-up. The questionnaire package includes the Decisional Conflict Scale, Control Preferences Scale, Quality-Quantity Questionnaire, treatment expectations, European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), EORTC financial toxicity items, Work Ability Index, Functional Assessment of Cancer Therapy-General (FACT-G) items and Decisional Regret Scale. Clinical data will be extracted from patient records and linked with questionnaire responses. The primary outcome measure is the change in global HRQoL from baseline to after cycle 4 of first-line chemotherapy (based on published data showing that patients with advanced STS complete a median number of four cycles of first-line chemotherapy).

Ethics and dissemination: Heath Research Authority and Research Ethics Committee (REC 17/NI/0197). Results from the Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy (HOLISTIC) study will be published in peer-reviewed journals and disseminated at local, national and international conferences. We will also present our findings at any appropriate patient meetings and involve patients in study-related publications.

Trial registration number: NCT03621332.

Keywords: adult oncology; chemotherapy; sarcoma.

Conflict of interest statement

Competing interests: RLJ is a consultant for: Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar. WTAvDG has received research grants from Novartis and has been on advisory board from Bayer. The other authors declare that they have no competing interests.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Burningham Z, Hashibe M, Spector L, et al. . The epidemiology of sarcoma. Clin Sarcoma Res 2012;2:14. 10.1186/2045-3329-2-14
    1. Brouns F, Stas M, De Wever I. Delay in diagnosis of soft tissue sarcomas. Eur J Surg Oncol 2003;29:440–5. 10.1016/S0748-7983(03)00006-4
    1. Coindre JM, Terrier P, Guillou L, et al. . Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of cancer centers sarcoma group. Cancer 2001;91:1914–26. 10.1002/1097-0142(20010515)91:10<1914::aid-cncr1214>;2-3
    1. Ferguson PC, Deheshi BM, Chung P, et al. . Soft tissue sarcoma presenting with metastatic disease: outcome with primary surgical resection. Cancer 2011;117:372–9. 10.1002/cncr.25418
    1. Nijhuis PH, Schaapveld M, Otter R, et al. . Epidemiological aspects of soft tissue sarcomas (STS)--consequences for the design of clinical STS trials. Eur J Cancer 1999;35:1705–10. 10.1016/S0959-8049(99)00152-5
    1. Dangoor A, Seddon B, Gerrand C, et al. . Uk guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res 2016;6:20. 10.1186/s13569-016-0060-4
    1. Italiano A, Mathoulin-Pelissier S, Cesne AL, et al. . Trends in survival for patients with metastatic soft-tissue sarcoma. Cancer 2011;117:1049–54. 10.1002/cncr.25538
    1. Tap WD, Papai Z, Van Tine BA, et al. . Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (th CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2017;18:1089–103. 10.1016/S1470-2045(17)30381-9
    1. Schöffski P, Cornillie J, Wozniak A, et al. . Soft tissue sarcoma: an update on systemic treatment options for patients with advanced disease. Oncol Res Treat 2014;37:355–62. 10.1159/000362631
    1. Judson I, Verweij J, Gelderblom H, et al. . Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol 2014;15:415–23. 10.1016/S1470-2045(14)70063-4
    1. Schlemmer M, Reichardt P, Verweij J, et al. . Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer 2008;44:2433–6. 10.1016/j.ejca.2008.07.037
    1. Mir O, Domont J, Cioffi A, et al. . Feasibility of metronomic oral cyclophosphamide plus prednisolone in elderly patients with inoperable or metastatic soft tissue sarcoma. Eur J Cancer 2011;47:515–9. 10.1016/j.ejca.2010.11.025
    1. Bottomley A. The cancer patient and quality of life. Oncologist 2002;7:120–5. 10.1634/theoncologist.7-2-120
    1. Shrestha A, Martin C, Burton M, et al. . Quality of life versus length of life considerations in cancer patients: a systematic literature review. Psychooncology 2019;28:1367–80. 10.1002/pon.5054
    1. Kluetz PG, Slagle A, Papadopoulos EJ, et al. . Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res 2016;22:1553–8. 10.1158/1078-0432.CCR-15-2035
    1. Younger E, Wilson R, van der Graaf WTA, et al. . Health-Related quality of life in patients with sarcoma: enhancing personalized medicine. J Clin Oncol 2018;36:1642–3. 10.1200/JCO.2018.77.9819
    1. Gough NJ, Smith C, Ross JR, et al. . Symptom burden, survival and palliative care in advanced soft tissue sarcoma. Sarcoma 2011;2011:1–8. 10.1155/2011/325189
    1. Bottomley A, Pe M, Sloan J, et al. . Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards. Lancet Oncol 2016;17:e510–4. 10.1016/S1470-2045(16)30510-1
    1. Basch E. The rationale for collecting patient-reported symptoms during routine chemotherapy. Am Soc Clin Oncol Educ Book 2014:161–5. 10.14694/EdBook_AM.2014.34.161
    1. Di Maio M, Basch E, Bryce J, et al. . Patient-Reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol 2016;13:319–25. 10.1038/nrclinonc.2015.222
    1. Basch E, Jia X, Heller G, et al. . Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 2009;101:1624–32. 10.1093/jnci/djp386
    1. Basch E. Patient-Reported Outcomes - Harnessing Patients' Voices to Improve Clinical Care. N Engl J Med 2017;376:105–8. 10.1056/NEJMp1611252
    1. Davidson D, Barr RD, Riad S, et al. . Health-Related quality of life following treatment for extremity soft tissue sarcoma. J Surg Oncol 2016;114:821–7. 10.1002/jso.24424
    1. Sachsenmaier SM, Ipach I, Kluba T. Quality of life, physical and mental status and Contentment of patients with localized soft tissue or bone sarcoma: a questionnaire analysis. Orthop Rev 2015;7:5920. 10.4081/or.2015.5920
    1. Fernandez-Pineda I, Hudson MM, Pappo AS, et al. . Long-Term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude lifetime cohort study. J Cancer Surviv 2017;11:1–12. 10.1007/s11764-016-0556-1
    1. McDonough J, Eliott J, Neuhaus S, et al. . Health-Related quality of life, psychosocial functioning, and unmet health needs in patients with sarcoma: a systematic review. Psychooncology 2019;28:653–64. 10.1002/pon.5007
    1. Reichardt P, Leahy M, Garcia Del Muro X, et al. . Quality of life and utility in patients with metastatic soft tissue and bone sarcoma: the sarcoma treatment and burden of illness in North America and Europe (sabine) study. Sarcoma 2012;2012:74027910.1155/2012/740279
    1. van der Graaf WTA, Blay J-Y, Chawla SP, et al. . Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012;379:1879–86. 10.1016/S0140-6736(12)60651-5
    1. Hudgens S, Forsythe A, Kontoudis I, et al. . Evaluation of quality of life at progression in patients with soft tissue sarcoma. Sarcoma 2017;2017:237213510.1155/2017/2372135
    1. Berry V, Basson L, Bogart E, et al. . REGOSARC: regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis. Cancer 2017;123:2294–302. 10.1002/cncr.30661
    1. Demetri GD, von Mehren M, Jones RL, et al. . Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol 2016;34:786–93. 10.1200/JCO.2015.62.4734
    1. van de Poll-Franse LV, Horevoorts N, van Eenbergen M, et al. . The patient reported outcomes following initial treatment and long term evaluation of survivorship registry: scope, rationale and design of an infrastructure for the study of physical and psychosocial outcomes in cancer survivorship cohorts. Eur J Cancer 2011;47:2188–94. 10.1016/j.ejca.2011.04.034
    1. Coons SJ, Eremenco S, Lundy JJ, et al. . Pro) data electronically: the past, present, and promise of ePRO measurement in clinical trials. Patient 2015;8:301–9.
    1. Gwaltney CJ, Shields AL, Shiffman S. Equivalence of electronic and paper-and-pencil administration of patient-reported outcome measures: a meta-analytic review. Value Health 2008;11:322–33. 10.1111/j.1524-4733.2007.00231.x
    1. Muehlhausen W, Doll H, Quadri N, et al. . Equivalence of electronic and paper administration of patient-reported outcome measures: a systematic review and meta-analysis of studies conducted between 2007 and 2013. Health Qual Life Outcomes 2015;13:167. 10.1186/s12955-015-0362-x
    1. Chew LD, Griffin JM, Partin MR, et al. . Validation of screening questions for limited health literacy in a large Va outpatient population. J Gen Intern Med 2008;23:561–6. 10.1007/s11606-008-0520-5
    1. Husson O, Mols F, Fransen MP, et al. . Low subjective health literacy is associated with adverse health behaviors and worse health-related quality of life among colorectal cancer survivors: results from the profiles registry. Psychooncology 2015;24:478–86. 10.1002/pon.3678
    1. Cocks K, King MT, Velikova G, et al. . Evidence-Based guidelines for determination of sample size and interpretation of the European organisation for the research and treatment of cancer quality of life questionnaire core 30. J Clin Oncol 2011;29:89–96. 10.1200/JCO.2010.28.0107
    1. EORTC Computerised Adaptive Tests (CAT) Item library: financial difficulties. Available: [Accessed 29 Aug 2019].
    1. Paul CL, Hall AE, Carey ML, et al. . Access to care and impacts of cancer on daily life: do they differ for metropolitan versus regional hematological cancer survivors? J Rural Health 2013;29 Suppl 1:s43–50. 10.1111/jrh.12020
    1. Cella DF, Tulsky DS, Gray G, et al. . The functional assessment of cancer therapy scale: development and validation of the general measure. J Clin Oncol 1993;11:570–9. 10.1200/JCO.1993.11.3.570
    1. Bonomi AE, Cella DF, Hahn EA, et al. . Multilingual translation of the functional assessment of cancer therapy (fact) quality of life measurement system. Qual Life Res 1996;5:309–20. 10.1007/BF00433915
    1. Pearman TP, Beaumont JL, Mroczek D, et al. . Validity and usefulness of a single-item measure of patient-reported bother from side effects of cancer therapy. Cancer 2018;124:991–7. 10.1002/cncr.31133
    1. Degner LF, Sloan JA, Venkatesh P. The control preferences scale. Can J Nurs Res 1997;29:21–43.
    1. Singh JA, Sloan JA, Atherton PJ, et al. . Preferred roles in treatment decision making among patients with cancer: a pooled analysis of studies using the control preferences scale. Am J Manag Care 2010;16:688–96.
    1. Henrikson NB, Davison BJ, Berry DL. Measuring decisional control preferences in men newly diagnosed with prostate cancer. J Psychosoc Oncol 2011;29:606–18. 10.1080/07347332.2011.615383
    1. Cuypers M, Lamers RED, de Vries M, et al. . Prostate cancer survivors with a passive role preference in treatment decision-making are less satisfied with information received: results from the profiles registry. Urol Oncol 2016;34:482.e11–482.e18. 10.1016/j.urolonc.2016.06.015
    1. O’Connor AM. Decisional conflict scale. Available: [Accessed 29 Aug 2019].
    1. Koedoot N, Molenaar S, Oosterveld P, et al. . The decisional conflict scale: further validation in two samples of Dutch oncology patients. Patient Educ Couns 2001;45:187–93. 10.1016/S0738-3991(01)00120-3
    1. Stiggelbout AM, de Haes JC, Kiebert GM, et al. . Tradeoffs between quality and quantity of life: development of the QQ questionnaire for cancer patient attitudes. Med Decis Making 1996;16:184–92. 10.1177/0272989X9601600211
    1. Weeks JC, Catalano PJ, Cronin A, et al. . Patients' expectations about effects of chemotherapy for advanced cancer. N Engl J Med 2012;367:1616–25. 10.1056/NEJMoa1204410
    1. Nipp RD, Greer JA, El-Jawahri A, et al. . Coping and prognostic awareness in patients with advanced cancer. J Clin Oncol 2017;35:2551–7. 10.1200/JCO.2016.71.3404
    1. Ilmarinen J. The work ability index (WAI). Occup Med 2007;57:160 10.1093/occmed/kqm008
    1. Gregorowitsch ML, van den Bongard HJGD, Couwenberg AM, et al. . Self-Reported work ability in breast cancer survivors; a prospective cohort study in the Netherlands. Breast 2019;48:45–53. 10.1016/j.breast.2019.08.004
    1. O’Connor AM. Decisional regret scale. Available: [Accessed 29 Aug 2019].
    1. Leiden University Medical Center Dutch translation of decisional regret scale, 2010. Available: [Accessed 10 Feb 2020].
    1. Karavasilis V, Seddon BM, Ashley S, et al. . Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma: retrospective analysis and identification of prognostic factors in 488 patients. Cancer 2008;112:1585–91. 10.1002/cncr.23332
    1. Fayers PM, Aaronson NK, et al. , Bottomley A, on behalf of the EORTC Quality of Life Group . The EORTC QLQ-C30 scoring manual. 3rd Edn Brussels: European Organisation for Research and Treatment of Cancer, 2001.

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