Volumetric Response of Limited Brain Metastatic Disease to Focal Hypofractionated Radiation Therapy

Abstract

Background: This is a retrospective study aimed at assessing the volumetric response, morbidity and failure rates of hypofractionated radiation therapy (HFRT) for definitive focal management of limited brain metastasis. Methods: Patients managed with HFRT for unresected limited metastatic (≤10 lesions) brain disease were entered into an ethics-approved database. Included patients had been deemed unsuitable for surgical resection, and lesions managed with prior radiation therapy were excluded. HFRT was delivered using IMRT or VMAT with 25 Gy or 30 Gy in five fractions. Individual lesions had volumetric assessment performed at three timepoints. The primary endpoint was the 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 rates 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 32 (25.8%) patients alive at censure. Median overall survival was 7.3 months with 36.3% survival at 12 months. Superior survival was predicted by smaller GTV0 (p = 0.003) and increased percentage of volumetric response (p < 0.001). Systemic therapy was delivered to 81.5% of patients. At one month post-HFRT, 206 metastases (88.4%) were available for assessment and at seven months post-HFRT, 118 metastases (50.6%) were available. Median metastasis volume at GTV0 was 1.6 cm3 (range: 0.1-19.1). At GTV1 and GTV7, this reduced to 0.7 cm3 (p < 0.001) and 0.3 cm3 (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 identified in 4.3% of lesions and radiation necrosis in 3.9%. Conclusion: HFRT is an effective therapy for limited metastatic disease in the brain to maximise initial volumetric response whilst minimising toxicity.