An International, Multi-Institutional Analysis of Clinical Outcomes Following Stereotactic Radiosurgery for the Treatment of Brain Metastases from Sarcoma Primaries

Summary: There is a paucity of data on treatment outcomes following stereotactic radiosurgery (SRS) for brain metastases from sarcoma primaries. This is further exacerbated by clinical heterogeneity among sarcoma histologies. The International Radiosurgery Research Foundation member-sites were queried for patients with brain metastases from sarcoma primaries treated with definitive or post-operative stereotactic radiosurgery (SRS) with ≥1 post-treatment follow up evaluation. Overall survival (OS) was calculated from end of treatment (EOT) to death or last follow-up, and local control (LC) was calculated from EOT to local recurrence, or death, or last follow-up via Kaplan-Meier analysis. Initial univariate analyses (UVA) examined prognostic factors associated with LC and OS via log-rank t-tests, with subsequent multivariate analyses (MVA) performed via a Cox proportional hazards model. From 18 participating sites, 146 patients with 309 brain metastases were identified. Median patient age was 47 years (range: 3-92). Median KPS was 80% (range: 40-100%). The most common histologies were leiomyosarcoma (53 metastases), pleomorphic sarcoma (51 metastases), undifferentiated/unclassified sarcoma (48 lesions), and Ewing sarcoma (26 metastases). Two-hundred-thirty lesions were treated with single fraction SRS (SF-SRS) with a median dose of 20 Gy (15-24 Gy). Ninety-five patients had extra-cranial metastases, including 75 oligometastatic patients. Following SRS, median OS was 11.2 months (95% CI: 7.8-16.1 months). One- and 2-year OS and LC rates were 47.7% and 37.3%, and 78.3% and 62.2%, respectively. On UVA, superior 1-year OS was noted among leiomyosarcomas (69.7% vs. 42.6%; p=0.02) with poorer outcomes among pleomorphic histologies (10.5% vs. 50.7%; p=0.002). Pleomorphic histologies were associated with poorer OS on MVA (HR = 3.13, p = 0.006). On MVA, LC was inferior among patients of age ≥ 45 years (HR = 3.78, p< 0.001) and superior among leiomyosarcomas (HR = 0.31, p=0.03). We prognosticated OS based on a point system for non-leiomyosarcoma histology and progressive extracranial metastases. One-year OS for patients with 0, 1, and 2 points were 78.6%, 47.9%, and 38.8%, respectively. LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age < 45 years. OS was driven by non-leiomyosarcoma histology and the presence of progressive extracranial disease. Prospective trials or registries are warranted to further elucidate optimal treatment approaches and guide clinical decision making, with aggressive local ablative therapies particularly meriting consideration for those < 45 years, patients with non-progressive extra-cranial metastases, and those with either leiomyosarcomas or non-pleomorphic histologies. John G.. Roubil, MD (Presenting Author) - Massey Comprehensive Cancer Center at VCU Health; Joshua D.. Palmer, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center; Jason P.. Sheehan, MD PhD (Co-Author) - Department of Neurological Surgery, University of Virginia Health System; Raj Singh, MD (Co-Author) - Department of Radiation Oncology, The James Cancer Hospital and Solove Research Institute at The Ohio State University Wexner Medical Center