Measuring what matters MOST: validation of the Measure of Ovarian Symptoms and Treatment, a patient-reported outcome measure of symptom burden and impact of chemotherapy in recurrent ovarian cancer
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Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit.
GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with ≥ 3 lines of prior chemotherapy (PPS-ROC ≥ 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients’ cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearman’s correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed.
Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC ≥ 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy.
The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test–retest reliability.
KeywordsOvarian cancer Recurrent ovarian cancer Platinum sensitive Platinum resistant Platinum refractory Symptom burden Symptom benefit Magnitude of clinical benefit Net health benefit Patient-reported outcome PRO Patient-reported outcome measure PROM Quality of life QOL Health-related quality of life HRQOL HRQL
In Australia, the study was coordinated by the NHMRC Clinical Trials Centre, University of Sydney. The Cancer Research UK and UCL Cancer Trials Centre coordinated UK participation in the study.
In Australia the study was supported by NHMRC grants 1063012 and 570,893. In the United Kingdom (UK), this was a National Institute for Health Research (NIHR) study jointly funded by Target Ovarian Cancer (UCL-P001AL) and the Cancer Research UK and UCL Cancer Trials Centre (Programme Grant C444/A15953). Professor King is supported by the Australian Government through Cancer Australia. Professor Friedlander is supported by an NHMRC Program grant. Dr Anne Lanceley was assisted by the National Institute for Health Research (NIHR) UCLH/UCL Biomedical Research Centre which is supported by the Department of Health.
Compliance with ethical standards
Conflict of interest
The authors declared that they have no conflicts of interest in relation to the material presented in this paper.
GCIG-SBS was led and coordinated by the Australian New Zealand Gynecological Oncology Group (ANZGOG) and National Health and Medical Research Council (NHMRC) Clinical Trials Centre, University of Sydney, in collaboration with the GCIG Symptom Benefit Committee. The trial was registered on the Australian New Zealand Clinical Trials Registry (ANZCTR 12607000603415). The study was performed in accordance with the NHMRC Statement on Ethical Conduct in Research Involving Humans and the Declaration of Helsinki, with ethics approval at all participating sites, and signed, written, and informed consent was obtained from all participants.
- 3.Friedlander, M. L., Mercieca-Bebber, R., & King, M. T. (2016). Patient-reported outcomes (PRO) in ovarian cancer clinical trials—lost opportunities and lessons learned. 27(Suppl 1), i66–i71, doi: 10.1093/annonc/mdw080.
- 4.Wilson, M. K., Pujade-Lauraine, E., Aoki, D., Mirza, M. R., Lorusso, D., Oza, A. M., et al. (2016). 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: Recurrent Disease. Annals of Oncology, 19.Google Scholar
- 6.du Bois, A., Quinn, M., Thigpen, T., Vermorken, J., Avall-Lundqvist, E., Bookman, M., et al. (2005). 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Annals of Oncology, 16, 7–12. doi: 10.1093/annonc/mdi961.CrossRefGoogle Scholar
- 7.Cherny, N. I., Sullivan, R., Dafni, U., Kerst, J. M., Sobrero, A., Zielinski, C., et al. (2005). A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Annals of Oncology, 26(8), 1547–1573.CrossRefGoogle Scholar
- 9.Friedlander, M. L., Stockler, M., O’Connell, R., Voysey, M., Oza, A., Gillies, K., et al. (2014). Symptom burden and outcomes of patients with platinum resistant/refractory recurrent ovarian cancer: a reality check: results of stage 1 of the gynecologic cancer intergroup symptom benefit study. International Journal of Gynecological Cancer, 24(5), 857–864. doi: 10.1097/IGC.0000000000000147.CrossRefPubMedGoogle Scholar
- 10.King, M. T., Stockler, M. R., Butow, P., O’Connell, R., Voysey, M., Oza, A. M., et al. (2014). Development of the measure of ovarian symptoms and treatment concerns: aiming for optimal measurement of patient-reported symptom benefit with chemotherapy for symptomatic ovarian cancer. International Journal of Gynecological Cancer, 24(5), 865–873. doi: 10.1097/IGC.0000000000000167.CrossRefPubMedGoogle Scholar
- 11.FDA (2009). Food and drug administration. guidance for industry on patient-reported outcome measures: Use in medical product development to support labeling claims. Federal Register, 74(235), 65132–65133.Google Scholar
- 12.Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., et al. (1993). The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute, 85(5), 365–376.CrossRefPubMedGoogle Scholar
- 13.Greimel, E., Bottomley, A., Cull, A., Waldenstrom, A. C., Arraras, J., Chauvenet, L., et al. (2003). An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-OV28) in assessing the quality of life of patients with ovarian cancer. European Journal of Cancer (Oxford, England: 1990), 39(10), 1402–1408.CrossRefGoogle Scholar
- 14.Basen-Engquist, K., Bodurka-Bevers, D., Fitzgerald, M. A., Webster, K., Cella, D., Hu, S., et al. (2001). Reliability and validity of the functional assessment of cancer therapy-ovarian. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 19(6), 1809–1817.CrossRefGoogle Scholar
- 15.Beaumont, J., Yount, S., Lalla, D., Lubeck, D., Derynck, M., & Karlan, B. e. a. (2007). Validation of the functional assessment of cancer therapy-Ovarian (FACT-O) symptom index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer. ASCO Annual Meeting Proceedings Part I. 25, 18S.Google Scholar
- 18.Sehouli, J., Stengel, D., Harter, P., Kurzeder, C., Belau, A., Bogenrieder, T., et al. (2011). Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Journal of Clinical Oncology, 29(2), 242–248. doi: 10.1200/JCO.2009.27.8911.CrossRefPubMedGoogle Scholar
- 19.Dewolf, L., Koller, M., Velikova, G., Johnson, C., Scott, N., Bottomley, A., et al. (2009). EORTC Quality of Life Group Translation Procedure (3rd edn.). ed.). Brussels: EORTC Publicatiions.Google Scholar
- 25.Cohen, J. (1988). Statistical power analysis for the behavioral sciences, Abington: Routledge.Google Scholar
- 27.Cocks, K., King, M. T., Velikova, G., St-James, Martyn, Fayers, M., P. M., & Brown, J. M. (2011). 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. Journal of Clinical Oncology, 29(1), 89–96. doi: 10.1200/JCO.2010.28.0107.CrossRefPubMedGoogle Scholar
- 30.Basch, E., Jia, X., Heller, G., Barz, A., Sit, L., Fruscione, M., et al. (2009). Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. Journal of the National Cancer Institute, 101(23), 1624–1632. doi: 10.1093/jnci/djp386.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Stuart, G. C., Kitchener, H., Bacon, M., duBois, A., Friedlander, M., Ledermann, J., et al. (2011). 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. International Journal of Gynecological Cancer, 21(4), 750–755.CrossRefPubMedGoogle Scholar