The Added Value of Analyzing Pooled Health-Related Quality of Life Data: A Review of the EORTC PROBE Initiative.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. METHODS: The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. RESULTS: Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomiting (P = .01), nausea (P < .001), and constipation (P = .01). Greater understanding of the association between symptom and/or functioning scales was developed by identifying physical, psychological, and gastrointestinal clusters. Additionally, minimally important differences in interpreting HRQOL changes for improvement and deterioration were found to vary across different patient populations and disease stages. Finally, HRQOL scores are statistically significantly affected by deviations from the intended time point at which the questionnaire is completed. CONCLUSIONS: The use of existing pooled data shows that it is possible to learn about general aspects of cancer HRQOL and methodology. Our work shows that setting up international pooled datasets holds great promise for understanding patients' unmet psychosocial needs and calls for additional empirical investigation to improve clinical care and understand cancer through retrospective HRQOL analyses.

The effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients.

BACKGROUND: Cancer incidence increases exponentially with advancing age, cancer patients live longer than in the past, and many new treatments focus on stabilizing disease and HRQOL. The objective of this study is to examine how cancer affects patients' HRQOL and whether their HRQOL is age-dependent. METHODS: Data from 25 EORTC randomized controlled trials was pooled. EORTC QLQ-C30 mean scores for the cancer cohort and five general population cohorts were compared to assess the impact of cancer on patients' HRQOL. Within the cancer cohort, multiple linear regressions (two-sided level P-value = 0.05 adjusted for multiple testing.) were used to investigate the association between age and HRQOL, adjusted for gender, WHO performance status (PS), distant metastasis and stratified by cancer site. A difference of 10 points on the 0-100 scale was considered clinically important. RESULTS: Cancer patients generally have worse HRQOL compared to the general population, but the specific HRQOL domains impaired vary with age. When comparing the cancer versus the general population, young cancer patients had worse financial problems, social and role functioning, while the older cancer groups had more appetite loss. Within the cancer cohort, HRQOL was worse with increasing age for physical functioning and constipation, and better with increasing age for social functioning, insomnia and financial problems (all p < 0.05). CONCLUSION: HRQOL is impaired in cancer patients compared to the general population, but the impact on specific HRQOL domains varies by age. Within the cancer population, some HRQOL components improve with age while others deteriorate. Optimal care for older cancer patients should target HRQOL domains most relevant to this population.

A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites.

BACKGROUND: The objective of this study was to examine the prognostic value of baseline health-related quality of life (HRQOL) for survival with regard to different cancer sites using 1 standardized and validated patient self-assessment tool. METHODS: In total, 11 different cancer sites pooled from 30 European Organization for Research and Treatment of Cancer (EORTC) randomized controlled trials were selected for this study. For each cancer site, univariate and multivariate Cox proportional hazards modeling was used to assess the prognostic value (P< .05) of 15 HRQOL parameters using the EORTC Core Quality of Life Questionnaire (QLQ-C30). Models were adjusted for age, sex, and World Health Organization performance status and were stratified by distant metastasis. RESULTS: In total, 7417 patients completed the EORTC QLQ-C30 before randomization. In brain cancer, cognitive functioning was predictive for survival; in breast cancer, physical functioning, emotional functioning, global health status, and nausea and vomiting were predictive for survival; in colorectal cancer, physical functioning, nausea and vomiting, pain, and appetite loss were predictive for survival; in esophageal cancer, physical functioning and social functioning were predictive for survival; in head and neck cancer, emotional functioning, nausea and vomiting, and dyspnea were predictive for survival; in lung cancer, physical functioning and pain were predictive for survival; in melanoma, physical functioning was predictive for survival; in ovarian cancer, nausea and vomiting were predictive for survival; in pancreatic cancer, global health status was predictive for survival; in prostate cancer, role functioning and appetite loss were predictive for survival; and, in testis cancer, role functioning was predictive for survival. CONCLUSIONS: The current results demonstrated that, for each cancer site, at least 1 HRQOL domain provided prognostic information that was additive over and above clinical and sociodemographic variables.

Patient self-reports of symptoms and clinician ratings as predictors of overall cancer survival.

BACKGROUND: The National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) reporting system is widely used by clinicians to measure patient symptoms in clinical trials. The European Organization for Research and Treatment of Cancer's Quality of Life core questionnaire (EORTC QLQ-C30) enables cancer patients to rate their symptoms related to their quality of life. We examined the extent to which patient and clinician symptom scoring and their agreement could contribute to the estimation of overall survival among cancer patients. METHODS: We analyzed baseline data regarding six cancer symptoms (pain, fatigue, vomiting, nausea, diarrhea, and constipation) from a total of 2279 cancer patients from 14 closed EORTC randomized controlled trials. In each trial that was selected for retrospective pooled analysis, both clinician and patient symptom scoring were reported simultaneously at study entry. We assessed the extent of agreement between clinician vs patient symptom scoring using the Spearman and kappa correlation statistics. After adjusting for age, sex, performance status, cancer severity, and cancer site, we used Harrell concordance index (C-index) to compare the potential for clinician-reported and/or patient-reported symptom scores to improve the accuracy of Cox models to predict overall survival. All P values are from two-sided tests. RESULTS: Patient-reported scores for some symptoms, particularly fatigue, did differ from clinician-reported scores. For each of the six symptoms that we assessed at baseline, both clinician and patient scorings contributed independently and positively to the predictive accuracy of survival prognostication. Cox models of overall survival that considered both patient and clinician scores gained more predictive accuracy than models that considered clinician scores alone for each of four symptoms: fatigue (C-index = .67 with both patient and clinician data vs C-index = .63 with clinician data only; P <.001), vomiting (C-index = .64 vs .62; P = .01), nausea (C-index = .65 vs .62; P < .001), and constipation (C-index = .62 vs .61; P = .01). CONCLUSION: Patients provide a subjective measure of symptom severity that complements clinician scoring in predicting overall survival.