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 (P < .001). Neurologic symptoms at ICP were observed in 21.1%, 28.1%, and 50.0% of cases, respectively (P < .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.

Duke Scholars

Author John P. Kirkpatrick Radiation Oncology

Author Joseph Kamel Salama Radiation Oncology

Author Zachary James Reitman Radiation Oncology

Author Trey Carlton Mullikin Radiation Oncology

Author Scott Richard Floyd Radiation Oncology