Long-term outcomes with reduced-dose whole-brain radiotherapy and a stereotactic radiosurgery boost for primary central nervous system lymphoma

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized that reduced dose-WBRT (rd-WBRT) followed by a stereotactic radiosurgery (SRS) boost could provide durable disease control without significant adverse effects. METHODS: We retrospectively reviewed PCNSL patients treated with rd-WBRT plus an SRS boost at Duke University between 2008 and 2021. Progression-free survival and overall survival (OS) were estimated using competing risk and Kaplan–Meier methods. RESULTS: We identified 23 patients with pathologically confirmed PCNSL. Median age at diagnosis was 69 years (Q1Q3: 52–74) and median Karnofsky Performance Scale (KPS) was 80 (Q1Q3: 70–80). Median follow-up was 21 months. Median doses for rd-WBRT and SRS were 23.4 Gy (Q1Q3: 23.4–23.4) and 12 Gy (Q1Q3: 12–12.5), respectively. The cumulative incidence of intracranial progression at 2 years was 23% (95% CI: 8–42). Six patients (26%) developed distant radiographic progression while 2 patients (9%) developed both distant and local progression. Ten patients (44%) were alive without progression at last follow-up. By Kaplan–Meier estimate, the 2-year OS was 69% (95% CI: 46–84). There were no reported grade 3 + radiation-induced toxicities. CONCLUSIONS: The combination of rd-WBRT with an SRS boost appears well-tolerated with durable intracranial control. This approach may represent a treatment option for select patients, such as those with progressive or refractory disease. Further prospective studies are needed to validate these findings and determine whether this approach could be incorporated into consolidation strategies.