BACKGROUND: Our objective was to identify an optimal margin for SRS of brain metastases, minimizing toxicity and local recurrence. METHODS: Adult patients with 1-3 brain metastases, no previous brain radiotherapy and KPS >70 were eligible for this IRB-approved trial. Individual lesions were randomized to 1 or 3mm uniform expansion of the gross tumor volume (GTV) defined on MRI. The resulting planning target volume (PTV) was treated to 24, 18 or 15Gy marginal dose for PTV diameters <2, 2-2.9 and 3-4.0cm, respectively, using a LINAC-based radiosurgery system with 3D image guidance. The primary endpoint was local recurrence (LR.) Secondary endpoints included neurocognition (mini-mental state exam, Trailmaking tests A/B), quality of life (QOL, FACT-Br), radionecrosis (RN), distant failure in the brain (DF) and overall survival (OS). RESULTS: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. Median age was 61 years and median KPS 90, with the predominant histologies non-small-cell lung cancer (25 patients) and melanoma (8). 55, 19 and 6 lesions were treated with 24, 18 and 15Gy, respectively. PTV/GTV ratio, V12Gy and minimum dose to GTV were significantly higher in the 3mm group (all p < 0.01), while GTV was similar (p = 0.76.) At a median follow-up of 32.2 months, 11 patients are alive with median OS 10.6 months. One-year post SRS, DF was 45.7%. LR was observed in 3 of 69 lesions with sufficient follow-up imaging, (2 in the 1mm group, p = 0.51) with a one-year post-SRS LR rate of 6.7%. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3mm group, p = 0.10). Three months post-SRS, no significant change in neurocognition or QOL was observed (p > 0.05 for all measures). CONCLUSION: SRS was well-tolerated with low rates of LR in both cohorts. Given the higher potential risk of RN, a 1mm margin appears more appropriate.
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Subjects: Medical Oncology ; Neurology
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