Clinical Parameters Associated With Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-institutional Brain Metastases Cohort.

Purpose: Following initial stereotactic radiosurgery (SRS), risk factors for high-burden intracranial progression (ICP) necessitating whole brain radiation remain poorly characterized. We hypothesize that specific clinical parameters at initial SRS are associated with high-burden ICP-defined as either ≥5 brain metastases (BMs) (ICP5) or ≥11 BMs (ICP11).

Materials And Methods: Across 2 institutions, we retrospectively identified all patients completing an initial SRS course from January 2015 to December 2020. ICP was defined as any radiographic concern for distant and/or in-field progression. Overall survival (OS) and freedom from ICP were estimated via the Kaplan-Meier method. Cox models assessed the association between clinical parameters and freedom from ICP5 and ICP11.

Results: We identified 1383 patients completing SRS. Post-SRS ICP was identified for 555 (40.1%) patients: 72.6% had 1 to 4 progressive BMs, 11.5% had 5 to 10 BMs, and 15.9% had ≥11 new BMs. Among these groups, 12-month OS was 56.8% (95% CI: 52.1%-61.9%), 46.0% (95% CI: 35.1%-60.1%), and 38.7% (95% CI: 29.4%-50.9%), respectively ( < .001). Neurologic symptoms at ICP were observed in 21.1%, 28.1%, and 50.0% of cases, respectively ( .001). Oligometastatic disease at the time of SRS [ICP5: hazard ratio (HR) 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97], no pre-SRS immunotherapy (ICP11: HR 1.74, 95% CI: 1.03-2.97), receipt of post-SRS immunotherapy (ICP5: HR 0.60, 95% CI: 0.402-0.906; ICP11: HR 0.57, 95% CI: 0.332-0.988), and a single BM at initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84) were negative predictive factors of high-burden ICP.

Conclusions: High-burden ICP was associated with decreased OS and neurologic decline. Patients who had oligometastatic disease, who received post-SRS immunotherapy, who did not receive pre-SRS immunotherapy, and who had a single BM had improved freedom from high-burden ICP. These findings may justify consideration of upfront whole brain radiation for those at risk for high-burden ICP and prospective analysis of short-interval post-SRS surveillance in this population.