The impact of different stereotactic radiation therapy regimens for brain metastases on local control and toxicity

Purpose Stereotactic radiation therapy (SRT) enables focused, short course, high dose per fraction radiation delivery to brain tumors that are less ideal for single fraction treatment because of size, shape, or close proximity to sensitive structures. We sought to identify optimal SRT treatment regimens for maximizing local control while minimizing morbidity. Methods and materials We performed a retrospective review of patients treated with SRT for solid brain metastases using variable dose schedules between 2001 and 2011 at 3 academic hospitals. Endpoints included (1) local control, (2) acute toxicity (Common Toxicity Criteria for Adverse Events v3.0), and (3) symptomatic radionecrosis. Kaplan-Meier and a competing risks methodology were used to estimate the actuarial rate of local failure and assess the association of clinical and treatment covariates with time to local failure. Results A total of 156 patients was identified. Common tumor histologies included breast (21%), non-small cell lung (32%), melanoma (22%), small cell lung (9%), and renal cell carcinoma (6%). The majority of lesions were supratentorial (57%). Median target volume was 3.99 mL (range, 0.04-58.42). Median total SRT dose was 25 Gy (range, 12-36), median fractional dose was 5 Gy (range, 2.5-11), and median number of fractions was 5 (range, 2-10). Cumulative incidence of local progression at 3, 6, 12, 18, and 24 months was 11%, 22%, 29%, 34%, and 36%. Total prescription dose was the only factor significantly associated with time to local progression on univariate (P = .02) and multivariable analysis (P = .01, adjusted hazards ratio, 0.87). Five patients experienced seizures within 10 days of SRT and 5 patients developed radionecrosis. All patients with documented radionecrosis received prior radiation to the index lesion. Conclusions Our series of SRT for brain metastases found total prescription dose to be the only factor associated with local control. Both acute and long-term toxicity events from SRT were modest.