Michael J. Moravan, Scott Floyd, Trey C. Mullikin, Jamiluddin Qazi, Joseph K. Salama, Jim Leng, Muzamil Arshad, Zachary J. Reitman, Eugene J. Vaios, Steven J. Chmura, Christina Huang, Brahma Natarajan, John P. Kirkpatrick, Julian C. Hong, David Carpenter
Purpose/Objective(s) Following initial stereotactic radiosurgery (SRS), risk factors for high-burden intracranial progression (ICP) necessitating whole brain radiation (WBRT) 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/Methods Across two institutions, we retrospectively identified all patients completing an initial SRS course from 1/2015—12/2020. 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 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 1-4 progressive BMs, 11.5% had 5-10 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<0.001). Neurologic symptoms at ICP were observed in 21.1%, 28.1%, and 50.0% of cases, respectively (p<0.001). Oligometastatic disease at time of SRS (ICP5: 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. Conclusion High-burden ICP was associated with decreased OS and neurologic decline. Patients who had oligometastatic disease, received post-SRS immunotherapy, did not receive pre-SRS immunotherapy, and had a single BM had improved freedom from high burden ICP. These findings may justify consideration of upfront WBRT for those at risk for high-burden ICP and prospective analysis of short-interval post-SRS surveillance in this population.