Abstract 4675: Radiation therapy utilization and outcomes in primary and secondary central nervous system lymphoma

Abstract Background: Radiotherapy (RT) is an established consolidation strategy for primary CNS lymphoma (PCNSL). However, the role of RT in secondary CNSL (SCNSL) is unclear. Here, we describe RT doses, disease failure patterns, and survival outcomes in an RT-treated CNSL cohort. Methods: Patients treated with CNS-directed RT for CNSL at UCSD were identified by ICD-10 codes, RT course description, or radiation oncologist. Site of CNS disease failure was local (involving initial site) or distant (outside of initial site). Overall survival (OS) and CNS progression-free survival (CNS PFS) were evaluated from time of RT start using Kaplan-Meier. Outcomes were stratified by PCNSL vs SCNSL. Results: 30 patients (13 [43%] PCNSL, 17 [57%] SCNSL) and 39 total CNS-RT courses were included. Most received RT for relapsed/refractory disease (23, 77%) as opposed to definitive (6, 20%) or consolidative (1, 3%) intent. At the time of RT, 1 (3%) patient had CSF, 13 (43%) had ocular, and 12 (40%) had extracranial disease (6 progressive, 6 stable). Median RT dose was higher for PCNSL (40.5 Gy vs 30 Gy for SCNSL, p=.031). First course RT targets were whole-brain RT (WBRT; 17, 57%; 6 included orbits [3 electively]), orbits alone (10, 33%), focal (2, 7%), and spine (1, 3%). 17 patients relapsed, most only distantly (9 [53%] vs 5 [29%] locally). Only SCNSL patients had synchronous local and distant failures (3, 18%). 2 patients received focal RT to dura and did not progress. Of the 4 (36%) who relapsed after WBRT, 2 were local-only SCNSL failures, and 2 were distant-only PCNSL failures. Of the 4 (67%) who relapsed after WBRT + orbits, 3 failed in the parenchyma. Most of the 8 who relapsed after orbits RT alone had distant (5, 63%) failures, most (3, 60%) parenchymal. Those with ocular involvement received WBRT + orbits or orbital RT alone, most relapsing in the parenchyma (8, 62%). No ocular failures occurred in those without ocular disease at RT start. Median OS was longer for PCNSL vs SCNSL (18.6 months [95%CI 0.0-42.4] vs 6 months [95%CI 3.0-8.9]), respectively; log-rank p=.058). Median CNS PFS was similar between PCNSL vs SCNSL (2.83 months [95%CI 0.0-19.8] vs 4.41 months [95%CI 1.4-7.4], respectively; log-rank p=.256). 3 patients had systemic relapse preceding CNS relapse. Conclusions: Different disease failure patterns were seen in mostly relapsed/refractory SCNSL vs PCNSL receiving CNS-RT. Only SCNSL patients failed both distantly and locally, suggesting the inclusion of more comprehensive treatments alongside RT (e.g., systemic or intrathecal). As SCNSL received a lower RT dose and most patients suffering local failure were SCNSL, further dose optimization should be considered. Future studies will examine MRI predictors of disease failure patterns. Citation Format: Brianna Hostler, Jona A. Hattangadi-Gluth, Parag Sanghvi, Kathryn R. Tringale. Radiation therapy utilization and outcomes in primary and secondary central nervous system lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4675.