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Summary: Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM’s.

Background Cerebral venous thrombosis usually presents as dural sinus thrombosis. More rarely, it occurs in an isolated form (isolated cortical vein thrombosis; ICoVT). ICoVT is poorly recognized and underdiagnosed, and noninvasive imaging remains nebulous. The digital subtraction angiographic (DSA) patterns of ICoVT are neither well known nor documented. We present clinical and imaging details of the largest series of ICoVT, with all cases demonstrating both noninvasive imaging findings, along with angiographic confirmation. We propose a preliminary compilation of the DSA patterns of ICoVT. Methods We identified all patients with cerebral venous thrombosis at our institution between January 2013 and June 2019. Only patients in whom ICoVT was diagnosed and/or suspected with computed tomographic venography and/or magnetic resonance imaging/MR venogram with subsequent DSA confirmation were included. DSA imaging was reviewed for direct and indirect signs. Clinical data, outcomes, and follow‐up imaging were analyzed. Results We identified 109 patients with cerebral venous thrombosis; in 21 patients ICoVT was suspected on noninvasive imaging and eventually had DSA confirmation. Headache and focal neurological deficit were the most common presentations (each 67%). Ten patients (47%) presented with parenchymal changes due to ICoVT and 15 patients (71%) presented with subarachnoid hemorrhage. We identified 5 DSA patterns of ICoVT (3 direct; 2 indirect). Filling defects in cortical veins and the regional absence of cortical veins and decreased subcortical opacification were the most common patterns (52% and 90%, respectively). Sixteen patients (76%) were anticoagulated. Eighteen patients were discharged without disability or minor disability (84%). No deaths occurred. Conclusions Catheter angiography/venography may be important in diagnosing ICoVT, especially when magnetic resonance imaging/MR venogram is unclear. The angiographic patterns of ICoVT are presented.

Abstract Background Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1–4 brain metastases. Methods This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1–4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. Discussion Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival. Trial registration Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).