Quality of Life in Brain Metastases Radiation Trials: A Literature Review

Background: An estimated 20%–40% of cancer patients will develop brain metastases. Whole-brain radiotherapy (WBRT) is the standard treatment for patients with brain metastases. Although WBRT can reduce neurologic symptoms, the median survival following WBRT is between 3 and 6 months. Given this limited survival, it is important to consider quality of life (QOL) when treating patients with brain metastases. However, few studies have focused on QOL and improvement in patient-rated symptoms as primary outcomes. Objective: For an accurate measurement of the extent to which previous trials have utilized QOL tools to evaluate the efficacy of WBRT for treatment of brain metastases, we undertook a literature review to examine the common endpoints and QOL instruments used. Methods: We conducted a systematic search using the MEDLINE (1950 to December 2007) and Cochrane Central Register of Controlled Trials (4th quarter 2007) databases. Eligible studies investigated WBRT in one of the study arms. The following outcomes were included: median survival, overall survival, neurologic function, 1-year local control, and overall response; use of QOL instruments, performance status scales, and neurologic function assessments; and use of other assessment tools. Patient-rated QOL instruments were defined as those that strove to assess all dimensions of QOL; observer-rated performance instruments such as the Karnofsky performance status (KPS) were deemed to be performance scales. Results: We identified sixty-one trials that included WBRT as a treatment for brain metastases. Of these sixty-one trials, nine evaluated the treatment of a single brain metastasis, and fifty-two evaluated the treatment of multiple brain metastases. Although fifty-five of the trials employed a QOL instrument, few trials focused on QOL as an outcome. We found 23 different instruments used to evaluate QOL. The most commonly employed instrument was the KPS (n = 33), followed by various neurologic function classification scales (n = 21). A preponderance of the studies used 1 (n = 26, 43%) or 2 (n = 21, 34%) QOL instruments. A total of fourteen published trials on brain metastases included an evaluation of the study population’s QOL. Those trials included three that used the Functional Assessment of Cancer Therapy–General scale and Brain subscale instrument, three that used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (C30) and the Brain Cancer Module 20 instrument, two that used study-designed QOL instruments, one that used the Edmonton Symptom Assessment Scale, two that used the Spitzer Quality of Life index, and three that used the KPS to evaluate QOL. Some trials reported deterioration in QOL after WBRT in patients with poorer prognosis; other trials detected an improvement in QOL after WBRT in patients with better prognosis. Conclusions: To date, fourteen trials in brain metastases that have included an evaluation of the study population’s QOL have been published. Although some studies showed that certain parameters of QOL deteriorate after WBRT, other studies showed that QOL in patients with better prognosis is improved after WBRT. Because a standard, validated QOL instrument has not been used for this patient population, a comparison of findings concerning QOL between the studies is difficult. The present review emphasizes the need to include QOL measures in future WBRT clinical trials for brain metastases.