Volumetric Response of Brain Oligometastatic Disease to Focal Hypofractionated Radiation Therapy

Background: This study aimed to assess the volumetric response, morbidity and failure rates of hypofractionated radiation therapy (HFRT) for definitive focal management of brain oligometastatic disease. Methods: Patients managed with HFRT for unresected oligometastatic brain disease were entered into an ethics-approved database. HFRT was delivered using IMRT or VMAT with 30Gy or 25Gy in 5 fractions. Individual lesions had volumetric assessment performed at three timepoints. Primary endpoint was change of volume from baseline (GTV0) to one-month post-HFRT (GTV1); and to seven-months post-HFRT (GTV7). Secondary endpoints were local failure, survival, and rate of radiation necrosis. Results:One hundred and twenty-four patients with 233 lesions were managed with HFRT. Median follow-up was 23.5 months with thirty-two (25.8%) patients alive at censure. Median overall survival was 7.3 months, with 36.3% survival at 12 months, with superior survival predicted by GTV0 (p=0.003) and percentage volumetric response (p<0.001). Systemic therapy was delivered in 81.5% of cases. At one-month post-HFRT 206 metastases (88.4%) were available for assessment; at seven-months post-HFRT this had reduced to 118 metastases (50.6%). Median metastasis volume at GTV0 was 1.6cm3 (range: 0.1-19.1). At GTV1 and GTV7 this reduced to 0.7cm3 (p<0.001) and 0.3cm3 (p<0.001) respectively, correlating to percentage reductions of 54.9% and 83.3%. No significant predictors of volumetric response following HFRT were identified. Local failure was confirmed in 4.3% of lesions and radiation necrosis in 3.9%. Conclusion: HFRT is an effective method for oligometastatic disease in the brain to maximise initial volumetric response whilst minimising pseudoprogression and radiation necrosis.