Whole brain radiotherapy in patients with NSCLC and brain metastases

1960 www.thelancet.com Vol 388 October 22, 2016 Radiation oncologists are often challenged because of the paucity of randomised trials supporting their clinical practice. In terms of brain metastases treatment, it should be emphasised that there have been fi ve randomised trials assessing whole brain radiotherapy (WBRT): four studies assessing stereotactic radio therapy with or without WBRT for patients with four or less brain metastases, and the present trial by Paula Mulvenna and colleagues in The Lancet assessing optimum supportive care with or without WBRT in a much poorer prognostic population of patients with non-small-cell lung cancer (NSCLC). None of these trials has shown any survival improvement with WBRT, but the fi rst four have shown improved intracranial control with the addition of WBRT. It is only in small-cell lung cancer that prophylactic WBRT improves survival because emergence and development of brain metastases is prevented; but this does not apply to patients with NSCLC Because of advances in the management of NSCLC, the risk of developing brain metastases seems to increase as survival is prolonged. NSCLC management in 2016 still represents a real challenge because detectable brain metastases might be responsible for life-threatening symptoms and serious impairment of quality of life, possibly ameliorated with WBRT. Mulvenna and colleagues are to be congratulated for conducting this non-inferiority phase 3 trial assessing the omission of WBRT in patients with NSCLC and brain metastases. They chose quality-adjusted life-years (QALYs) as the primary outcome measure, and a group of 538 patients between 2007 and 2014 were randomly assigned to receive either WBRT (20 Gy in fi ve daily fractions) and optimal supportive care, including dexamethasone (n=269), or optimal supportive care alone (n=269). The benefi ts in terms of length of life were adjusted to refl ect the quality of life assessed with weekly questionnaires. 536 patients died by October, 2015. The authors concluded that there was no evidence of a diff erence in terms of QALYs, overall survival (hazard ratio [HR] 1·06, 95% CI 0·90–1·26), or quality of life; the median survival from randomisation was less than 3 months. The diff erence between the mean QALYs was 4·7 days (46·4 QALY days for the optimal supportive care plus WBRT group vs 41·7 QALY days for the optimal supportive care only group), with two-sided 90% CI of –12·7 to 3·3. There is no question that this is a large and well designed trial, and that patients were well assessed, with more than 90% of the expected follow-up forms and more than 80% of the quality-of-life forms received. It should be emphasised that owing to poor survival, only 289 (53%, 149 WBRT patients and 140 optimal supportive care patients who were assessed for quality of life at 4 weeks) and 97 (18%, 54 WBRT patients and 43 optimal supportive care patients assessed at 12 weeks) of all enrolled patients answered quality-oflife questionnaires at 4 weeks and 12 weeks, respectively. Should we then consider that there is no place for WBRT Whole brain radiotherapy in patients with NSCLC and brain metastases 3 Hansen ML, Jepsen RM, Olesen JB, et al. Thromboembolic risk in 16 274 atrial fi brillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. 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