Outcomes and the Role of Primary Histology Following LINAC-based Stereotactic Radiosurgery (SRS) and Fractionated Stereotactic Radiotherapy (FSRT) for Sarcoma Brain Metastases

Abstract

The brain is a relatively rare site of metastasis for sarcoma. Sarcoma is also known to be radioresistant, making standard WBRT less appealing. SRS/FSRT may provide better local control but effectiveness data are limited. In this single institution retrospective analysis, we evaluated our experience with LINAC-based SRS and FSRT for sarcoma brain metastases. Time to event analysis was performed with Kaplan-Meier estimates. Univariable (UVA) and multivariable (MVA) Cox regression analyses were performed to assess the impact of patient and disease characteristics on outcomes. Between 2003 and 2018, 24 patients were treated with 34 courses of SRS/FSRT to 58 discrete lesions. Median age at first treatment was 57 years (range 25-87). Systemic therapy was given in 22 patients (19 with cytotoxic, 8 with tyrosine kinase inhibition, and 5 with immunotherapy). The most common primary histologies were spindle cell sarcoma (n=15; 25%) and leiomyosarcoma (n=12; 21%). All patients also had concurrent extracranial metastases (most commonly in the lung, n=21; 88%) and median interval from initial diagnosis to diagnosis of brain metastases was 18.8 months (range 0-172.7). Sixteen patients presented with symptoms (most commonly headache, n=11). Forty-three lesions were treated with SRS to a median dose of 19 Gy (range 15-24) and 17 were treated with FSRT in 3 or 5 fractions to a median dose of 25 Gy (range 25-35). Median follow-up after brain metastases diagnosis was 7.3 months (range 0.2-53.9) for all treated lesions. Six and 12 month local control rates were 89% following stereotactic radiation. Four lesions failed: 2 in post-operative FSRT, 1 in intact FSRT, and 1 in intact SRS. All lesions that failed were of primary spindle cell histology (p<0.001). Distant brain control at 6 and 12 months was 59% and 34%, respectively. Following distant failure, 7 patients were retreated with additional SRS/FSRT and 1 was treated with WBRT. On UVA spindle cell histology had worse distant control (HR 25.8, 95% CI 3.1-536.4; p=0.003). Median overall survival following brain metastasis diagnosis was 6.1 months with 6 and 12 month OS rates of 50% and 38%, respectively. Factors predicting worse OS from brain metastases diagnosis on MVA included spindle cell histology (7.0, 95% CI 2.0-25.4; p=0.003) and KPS <90 (3.4, 95% CI 1.2-10.7; p=0.02). One patient experienced treatment-related symptoms (right sided weakness), which resolved with a steroid taper. In this largest series of sarcoma patients treated with stereotactic radiation, we find SRS/FSRT can provide good local control with minimal symptoms, despite a reputation for radioresistance. Further study is needed to determine the impact of primary histology on control rates and survival following brain metastases diagnosis.