A Pilot/Phase II Study of Stereotactic Radiosurgery for Brain Metastases Using Rational Dose Selection

Abstract

The selection of radiosurgical dose for brain metastases is not well defined by clinical trials. Therefore, we performed a prospective phase 2 study to determine the efficacy of a dose algorithm that modified RTOG 90-05 recommendations to take into account lesion volume, number of metastases, radiosensitive vs. radioresistant histology, and prior whole brain radiotherapy (WBRT). A total of 39 patients were enrolled on a phase II study (NCT02005614) between April 3, 2014 and November 21, 2016. Inclusion criteria required Karnofsky Performance Status ≥ 70. Prescription dose was selected based on tumor volume, whether the patient had prior WBRT and the relative radioresistance of the tumor. All treatments were delivered at our institution. Lesion response was recorded and patient-level response was evaluated by RECIST criteria. The median age of enrolled patients was 64 years (range, 34-88). Median overall survival (OS) was 11.4 months (95% CI 4.9-15.7). Age was the only significant variable associated with OS. When analyzing by patient, overall best response was stable disease (SD) in 20%, partial response (PR) for 45%, and complete response (CR) for 32%. 7 patients eventually developed progressive disease at a median of 6.5 months (range 3.4 –12.6 months). 6 (15%) patients developed symptomatic radiation necrosis requiring steroids or surgery, also with median time to occurrence of 6.5 months. Altogether, 174 metastases were treated. The median marginal dose was 18 Gy (range, 15-22 Gy) and the median total volume (i.e. the total volume of all treated metastases for each patient) was 0.51 cc (0.06-23.1 cc). Analyzing by lesion, a CR was seen in 24% of lesions at 3 months, 61% at 6 months, 67% at 9 months and 76% at 12 months. Eight lesions progressed, corresponding to a lesional control rate of 95%. Stereotactic Radiosurgery using our dose algorithm results in excellent local control. Radiation necrosis remains a significant problem after radiosurgical treatment using the doses selected in this study.