Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma

Background Primary central nervous system lymphoma (PCNSL) is rare, with a treatment backbone that typically includes high-dose methotrexate-based chemotherapy, with radiation often reserved for persistent or progressive disease. In this study, we report the outcomes of stereotactic radiosurgery (SRS) in patients with PCNSL to potentially defer whole brain radiotherapy (WBRT) or as salvage after WBRT. Methodology We performed a single-institution, retrospective review of 20 patients with PCNSL who received single-fraction or fractionated SRS to 32 lesions between September 1992 and July 2019. Results The median age at SRS was 67 years (interquartile range (IQR) = 56-74 years). The median Karnofsky Performance Status (KPS) at SRS was 80 (IQR = 50-80). In total, 18 (90%) patients received methotrexate-based chemotherapy prior to SRS, with a median of eight cycles (IQR = 5-10). A total of 10 patients received SRS for recurrent disease after chemotherapy and/or WBRT, nine patients received SRS for the persistent disease after chemotherapy alone, and one patient received up-front SRS. Overall, five patients received SRS following WBRT. The median SRS dose was 16 Gy (IQR = 14-22.5 Gy) in one fraction (IQR = 1-5 fractions). Eight patients (40%) were treated with consolidative pomalidomide or lenalidomide following SRS. The local control rate was 100% (32/32 lesions at a median follow-up of 15 months). In total, 13 of 16 (81%) patients with available follow-up experienced distant brain recurrence. The median time to distant failure following SRS was 10 months (IQR = 1-16 months). Three patients received salvage SRS, and three patients received salvage WBRT. The median overall survival from diagnosis was 39 months (95% confidence interval = 24-54 months). KPS at the time of SRS was significantly correlated with time to progression (p = 0.002). The use of lenalidomide or pomalidomide after SRS was associated with improved overall survival after SRS (three vs. 14 months, p = 0.035). Consolidative etoposide and cytarabine after initial methotrexate-based chemotherapy was also associated with improved survival following SRS (eight vs. 47 months, p = 0.028). Conclusions SRS offers effective local tumor control for patients with PCNSL; however, the majority of patients experience distant progression. SRS may have a role in the salvage setting for patients with recurrence after WBRT, or allow deferral of WBRT in select patients, although systemic therapy appears to strongly influence outcomes in this cohort.