CLRM-01 DETERMINANTS OF SYMPTOMATIC INTRACRANIAL PROGRESSION FOLLOWING AN INITIAL STEREOTACTIC RADIOSURGERY COURSE

To determine the prognostic significance of neurologic symptoms at progression for patients with brain metastases (BM) undergoing stereotactic radiosurgery (SRS), all patients completing an initial course of SRS between 1/2015 and 12/2020 were identified across two institutions. Intracranial progression (ICP) was recorded, with symptomatic ICP (SICP) defined as new/worsening neurologic symptoms without another etiology. Overall survival (OS), freedom from ICP (FFICP), and freedom from symptomatic ICP (FFSICP) were assessed via Kaplan-Meier method. For FFSICP, patients were censored at time of death or asymptomatic ICP. Logistic regression models tested parameter association to neurologic symptoms. Cox proportional hazard models tested parameters impacting FFICP and FFSICP. Among 1383 patients, median age was 63.4 years, 54.8% were female, and 45.6% had KPS ≥90. Common primary sites were non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 foci), and 53.4% had >1 BM. 26.1% patients had prior surgical resection, and 10.3% had WBRT. With a median follow up of 8.7 months, 504 (36%) and 194 (14%) experienced asymptomatic and symptomatic ICP respectively. OS was worse for patients experiencing SICP (median 10.2 vs 17.9 months, p<0.001). Among patients with ICP, SICP was associated with total treated tumor volume (per-ml, OR 1.01, 95% CI 1.00-1.02), while those with more recent MRI imaging and post-SRS systemic therapy was associated with asymptomatic ICP. Patients who received post-SRS chemotherapy (HR 0.64, 95% CI 0.45-0.90), immunotherapy (HR 0.49, 95% CI 0.34-0.71), or targeted therapy (HR 0.49, 95% CI 0.33-0.73) had better FFSCIP. Worse FFSCIP was associated with melanoma (HR 2.56, 95% CI 1.49-4.38), and greater than 2 BMs (HR 2.24, 95% CI 1.56-3.22). SICP is prognostic for OS, and is associated with melanoma, no systemic therapy post-SRS, and greater number of BMs. These data further support the use of SICP as a meaningful clinical endpoint.