Whole brain radiotherapy for brain metastases from non-small lung cancer: Quality of life (QoL) and overall survival (OS) results from the UK Medical Research Council QUARTZ randomised clinical trial (ISRCTN 3826061).

Background: Brain metastases affect up to 40% of patients with non-small cell lung cancer (NSCLC), and for inoperable cases whole brain radiotherapy (WBRT) and dexamethasone is standard treatment. However there are no randomised clinical trials to show whether WBRT improves either QoL or survival. Methods: A phase III randomised non-inferiority trial with a primary outcome measure of quality adjusted life years (QALYs). Patients with brain metastases from NSCLC (not suitable for resection or stereotactic radiotherapy) were randomly allocated to either optimal supportive care, including dexamethasone, plus WBRT 20 Gy/5f (OSC+WBRT) or OSC alone. QALYs were generated from OS and patients' weekly completion of the EQ-5D questionnaire. OSC alone was considered non-inferior to OSC+WBRT if not greater than 7 QALY days worse (80% power and a 1-sided 5% significance level required 534 patients.) Secondary outcome measures include sub-group analyses to identify/validate predictive classifications. Results: From 2007-2014 538 patients were recruited from 69 UK and 3 Australian centres. Baseline characteristics were balanced between arms and reflect everyday clinical practice: male 58%, median age 66 years (range 38 - 85), Karnofsky performance status <70 38%, 54% had extracranial metastases, 30% had a solitary brain metastasis and 59% diagnosed with brain metastases within 28 days of randomisation. By January 2015 522/538 patients had died. There was no significant difference in OS from randomisation (hazard ratio 1.05 (95% CI 0.89 - 1.26) median survival OSC+WBRT v OSC (65 v 57 days)), overall QoL or steroid use between the 2 groups. The difference between the mean QALYs was -1.9 days (OSC+WBRT 43.3 v OSC 41.4 QALY days), two-sided 90% confidence interval for difference - 9.1 to +6.6 QALY days. Conclusions: This is the only large randomised trial evaluating the utility of WBRT in this disease. Although the results include the pre-specified non-inferiority margin, the estimate of the difference in QALYs suggests WBRT provides no additional clinically significant benefit for this group of patients.