Carolyn Gotay

The Prognostic Significance of Patient-Reported Outcomes in Cancer Clinical Trials

PURPOSE Patient-reported outcomes (PROs), routinely collected as a part of cancer clinical trials, have been linked with survival in numerous clinical studies, but a comprehensive critical review has not been reported. This study systematically assessed the impact of PROs on patient survival after a cancer diagnosis within the context of clinical trials. DESIGN Cancer clinical trials that assessed baseline PROs and mortality were identified through MEDLINE (through December 2006) supplemented by the Cochrane database, American Society of Clinical Oncology/European Society for Medical Oncology abstracts and hand searches. Inclusion criteria were publication in English language and use of multivariate analyses of PROs that controlled for one or more clinical factors. Two raters reviewed each study, abstracted data, and assessed study quality; two additional raters verified abstractions. RESULTS In 36 of 39 studies (N = 13,874), at least one PRO was significantly associated with survival (P < .05) in multivariate analysis, with varying effect sizes. Studies of lung (n = 12) and breast cancer (n = 8) were most prevalent. The most commonly assessed PRO was quality of life, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 in 56% of studies. Clinical variables adjusted for included performance status (PS), treatment arm, stage, weight loss, and serum markers. Results indicated that PROs provide distinct prognostic information beyond standard clinical measures in cancer clinical trials. CONCLUSION PROs might be considered for stratification purposes in future trials, as they were often better predictors of survival than PS. Studies are needed to determine whether interventions that improve PROs also increase survival and to identify explanatory mechanisms through which PROs relate to survival.

Beyond the Development of Health-Related Quality-of-Life (HRQOL) Measures: A Checklist for Evaluating HRQOL Outcomes in Cancer Clinical Trials—Does HRQOL Evaluation in Prostate Cancer Research Inform Clinical Decision Making?

PURPOSE The aim of this study was to evaluate whether the inclusion of health-related quality of life (HRQOL), as a part of the trial design in a randomized controlled trial (RCT) setting, has supported clinical decision making for the planning of future medical treatments in prostate cancer. MATERIALS AND METHODS A minimum standard checklist for evaluating HRQOL outcomes in cancer clinical trials was devised to assess the quality of the HRQOL reporting and to classify the studies on the grounds of their robustness. It comprises 11 key HRQOL issues grouped into four broader sections: conceptual, measurement, methodology, and interpretation. Relevant studies were identified in a number of databases, including MEDLINE and the Cochrane Controlled Trials Register. Both their HRQOL and traditional clinical reported outcomes were systematically analyzed to evaluate their consistency and their relevance for supporting clinical decision making. RESULTS Although 54% of the identified studies did not show any differences in traditional clinical end points between treatment arms and 17% showed a difference in overall survival, 74% of the studies showed some difference in terms of HRQOL outcomes. One third of the RCTs provided a comprehensive picture of the whole treatment including HRQOL outcomes to support their conclusions. CONCLUSION A minimum set of criteria for assessing the reported outcomes in cancer clinical trials is necessary to make informed decisions in clinical practice. Using a checklist developed for this study, it was found that HRQOL is a valuable source of information in RCTs of treatment in metastatic prostate cancer.

Patient-reported outcomes in cancer: a review of recent research and policy initiatives.

There is growing recognition that patient‐reported outcome (PRO) measures—encompassing, for example, health‐related quality of life—can complement traditional biomedical outcome measures (eg, survival, disease‐free survival) in conveying important information for cancer care decision making. This paper provides an integrated review and interpretation of how PROs have been defined, measured, and used in a range of recent cancer research and policy initiatives. We focus, in turn, on the role of PRO measurement in the evaluation and approval of cancer therapies, the assessment of cancer care in the community, patient‐provider decision making in clinical oncology practice, and population surveillance of cancer patients and survivors. The paper concludes with a discussion of future challenges and opportunities in PRO measure development and application, given the advancing state of the science in cancer outcomes measurement and the evolving needs of cancer decision makers at all levels.

Fear of cancer recurrence: a systematic literature review of self-report measures.

Prior research has shown that many cancer survivors experience ongoing fears of cancer recurrence (FCR) and that this chronic uncertainty of health status during and after cancer treatment can be a significant psychological burden. The field of research on FCR is an emerging area of investigation in the cancer survivorship literature, and several standardised instruments for its assessment have been developed.

Patient Self-Reports of Symptoms and Clinician Ratings as Predictors of Overall Cancer Survival

BACKGROUND The National Cancer Institutes 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 Cancers 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.

Definitions and conceptual models of quality of life

Over the past 30 years, quality of life has evolved into a respected construct for evaluating the effectiveness of treatment in health care. The field has grown in methodological rigor and in the sophistication of instrument development. Researchers in oncology have been at the forefront in the evaluation of quality of life, recognizing the need to assess outcomes more broadly than tumor response and length of survival. In 1985, quality of life was identified as a key parameter of efficacy to be used for approval of new anticancer drugs for advanced metastatic disease in the USA. In 1988, the Division of Cancer Treatment (CTEP) of the National Cancer Institute (USA) identified improving quality of life as one of its highest priorities. Quality-of-life endpoints are integral components of cancer clinical trials throughout the world, and are required for all phase III clinical trials by the National Cancer Institute of Canada Clinical Trials Group. But what is quality of life? The literature contains a bewildering array of characterizations. The term “quality of life” is commonly used to mean health status, physical functioning, symptoms, psychosocial adjustment, well-being, life satisfaction, or happiness. Introducing the term “health-related quality of life” has not solved the problem. Because the terms have meaning in everyday language, they are frequently used without explicit definition. At the heart of the problem is the very nature of the idea of quality of life, which is uniquely personal in its essence.

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

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.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients

BACKGROUND We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Behavior and Cancer Prevention

This paper reviews research on the effects of behavioral risk factors on cancer incidence, as well as behavioral interventions for cancer prevention. Risk factors discussed here--tobacco use, diet, physical activity, and obesity/energy balance--are all linked with cancer etiology, and effective behavioral interventions have been developed in all of these areas. The most effective interventions appear to incorporate various components; for example, including individual as well as family activities, and involving multiple community organizations in behavior-changing activities. Behavioral theories have guided the design of these interventions, providing support that certain influences on behavior, such as self-efficacy, problem-solving skills, and social support, are important regardless of the specific behavioral target. As illustrated by the recent lowered lung cancer incidence and mortality rates for men and women, behavior change is possible and effective in cancer prevention. Clinical guidelines have been established for behavioral aspects of treatments for smoking cessation, dietary guideline compliance, physical activity, and obesity reduction, and new tools for dissemination of effective intervention materials will be helpful in increasing their use. Documenting the cost-effectiveness of behavioral interventions, using new technology interventions, and building on translational research to tailor interventions to individuals offer considerable promise for the future.

Are Exercise Programs Effective for Improving Health-Related Quality of Life Among Cancer Survivors? A Systematic Review and Meta-Analysis

PURPOSE/OBJECTIVES To evaluate the effectiveness of exercise interventions on overall health-related quality of life (HRQOL) and its domains among cancer survivors who have completed primary treatment. DATA SOURCES 11 electronic databases were searched from inception (dates varied) to October 2011. The authors also identified eligible trials through a search of additional sources. DATA SYNTHESIS 40 trials with 3,694 participants met the inclusion criteria. At 12 weeks, cancer survivors exposed to exercise interventions had greater positive improvement in overall HRQOL (standardized mean difference [SMD] 0.48; 95% confidence interval [CI] [0.16, 0.81]), emotional well-being (SMD 0.33; 95% CI [0.05, 0.61]), and social functioning (SMD 0.45; 95% CI [0.02, 0.87]); and had a significant reduction in anxiety (SMD -0.26; 95% CI [-0.44, -0.07]) and fatigue (SMD -0.82; 95% CI [-1.5, -0.14]). CONCLUSIONS Exercise programs have a beneficial effect on HRQOL and most of its domains and can be integrated into the management plans for cancer survivors who have completed treatment. Future research is needed to help understand specific attributes of exercise programs that are beneficial for improving HRQOL within and across cancer types. IMPLICATIONS FOR NURSING Evidence presented in this review supports the inclusion of exercise programs in clinical guidelines for the management of cancer survivors who have completed treatment, such as the Oncology Nursing Societys Putting Evidence Into Practice resource.