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.

When should we define the response rates in the treatment of bone metastases by palliative radiotherapy?

AIMS: It is well established that palliative radiotherapy provides effective pain relief for symptomatic bone metastases, but controversy remains regarding the optimal dose fractionation. Several meta-analyses and systematic reviews of trials comparing the efficacy of single vs multiple fractionated radiotherapy schedules noted that it is difficult to reach a consensus when inconsistent response end point definitions are used. The purpose of this study was to determine when the most appropriate time to evaluate a response is. MATERIALS AND METHODS: Patients with symptomatic bone metastases treated with palliative radiotherapy between May 2003 and June 2005 were enrolled in the study. They were assessed with the Brief Pain Inventory at baseline, 1, 2 and 3 months after radiotherapy. Analgesic consumption during the preceding 24h was recorded and converted into an equivalent total daily dose of oral morphine. The response to radiotherapy was assessed using the International Bone Metastases Consensus end point definitions at 1, 2 and 3 months of follow-up. RESULTS: One hundred and ninety-nine patients were treated with palliative radiotherapy. All pain scores and functional interference items improved after radiotherapy. The proportion of evaluable patients with a complete response or a partial response increased between 1 month (58%) and 3 months of follow-up (67%). However, when considering intention-to-treat percentages, which take attrition into consideration, overall response rates dropped from 35% at 1 month, to 32% at 2 months, and finally 24% at 3 months. CONCLUSION: We conclude that 2 months after radiotherapy is the most appropriate time point to measure response rates for two reasons: (i) the maximum pain relief for some patients may take more than 4 weeks to achieve and (ii) attrition poses a major problem when response rates are measured at a later date. Future trials should use standardised criteria for end points to facilitate comparison and analysis across clinical trials. Given the limitations of this study, however, further investigations are needed to confirm the response time points for palliative cancer patients.

Symptom clusters in cancer patients with brain metastases.

AIM: To explore the presence of symptom clusters in patients with brain metastases. MATERIALS AND METHODS: Patients with brain metastases referred to an outpatient palliative radiotherapy clinic were asked to rate their symptom distress using the Edmonton Symptom Assessment Scale (ESAS). Baseline demographic data were obtained. To determine interrelationships between symptoms, a principal component analysis with 'varimax rotation' was carried out on the nine ESAS items. Follow-up was carried out by telephone 1, 2, 4, 8 and 12 weeks after radiation. RESULTS: Between January 1999 and January 2002, 170 patients with brain metastases provided complete baseline data on the ESAS. The most common primary cancer sites were lung, breast and gastrointestinal. Fatigue was the highest scored symptom, followed by a poor sense of well-being, anxiety, drowsiness and poor appetite. The four most prevalent symptoms were fatigue (91.7%), a poor sense of well-being (88.1%), drowsiness (82.2%) and anxiety (82.1%). Three symptom clusters were found at baseline. Cluster 1 included fatigue, drowsiness, shortness of breath and pain. Cluster 2 included anxiety and depression. Cluster 3 included poor appetite, nausea and a poor sense of well-being. Fatigue, nausea, drowsiness and poor appetite showed an overall increase in symptom severity over time; whereas fatigue, drowsiness and poor appetite were experienced to some extent by a greater proportion of patients at week 12 compared with baseline. Symptom clusters emerged in all weeks of follow-up, but consisted of different symptoms in each week. CONCLUSION: Symptom clusters seemed to exist in patients with brain metastases before and after whole brain radiotherapy. However, different symptoms clustered at various time points. The effectiveness of whole brain radiotherapy in providing palliative relief to patients with brain metastases needs to be explored with regards to symptom clusters.