PURPOSE: We performed a dose escalation trial of hypofractionated stereotactic radiosurgery (SRS) to determine the maximum tolerated dose (MTD) of 3-fraction SRS for brain metastases resection cavities. METHODS AND MATERIALS: Following surgical resection of a brain metastasis, patients were enrolled by SRS treatment volume onto 2 arms: Arm 1=4.2-14.1 cm RESULTS: From 2009 to 2014, 48 evaluable patients were enrolled. One (2%) patient had acute G3 toxicity
dose escalation proceeded to 33 Gy. No MTD was reached. Overall, 14 (29%) of 48 patients had G1-4 late radiation necrosis
G1 in 4(8%), G2 in 6(13%), G3 in 2(4%), and G4 in 2(4%). At the 33 Gy dose level, any grade necrosis was 58% in all 12 patients, 83% in the 6 patients on the larger volume Arm 2
no G3-4 necrosis occurred in smaller Arm 1 targets. With a median overall survival of 24 months (95% Confidence Interval (CI) 18-35), the 1-year cumulative incidence rates were: 10% (95%CI 3.8-21) for local progression, 48% (95%CI 33-61) for distant intracranial progression, and 13% (95%CI 5-24) for radiation necrosis. Nodular meningeal disease occurred in 15% (7 of 48) of patients. CONCLUSIONS: Grade 3-4 toxicity was 8% and no MTD was reached with dose-escalation to 33 Gy in 3 fractions. However, with a 58% incidence of G1-4 radiation necrosis at the 33 Gy level and 33% G3-4 necrosis at 30 Gy on Arm 2, a 3-fraction dose of 27-30 Gy for targets 2 to 3 cm and 27 Gy for targets 3 to 4 cm may provide the optimal balance between toxicity and tumor control. A dose of 33 Gy is reserved for cavities less than 3 cm where tumor control may benefit from higher doses.