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Background: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone.Methods: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants.Findings: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group.Interpretation: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy.Funding: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ⩽ 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02).Conclusions: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. [ABSTRACT FROM AUTHOR]