2813 - Clinical Outcomes of Whole Brain Radiotherapy for Methotrexate-Refractory Primary CNS Lymphoma
Presenter(s)
S. Murray1, G. Cederquist2, K. R. Tringale3, Z. R. Moore1, A. Deshane2, B. Fregonese1, M. Scordo4, L. Schaff5, C. Grommes5, J. Yahalom2, and B. S. Imber1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 3Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, 4Department of Medicine, Bone Marrow Transplant Division, Memorial Sloan Kettering Cancer Center, New York, NY, 5Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s): Primary CNS lymphoma (PCNSL) is a rare and aggressive subtype of non-Hodgkin lymphoma. While whole-brain radiotherapy (WBRT) is guideline-supported for consolidation, contemporary WBRT outcomes as salvage therapy after high-dose methotrexate (HD-MTX) failure are poorly characterized. Given the marked radiosensitivity of PCNSL, we hypothesized that WBRT can provide durable disease control in the salvage setting.
Materials/Methods: We performed a single-institution cohort study of adults with PCNSL treated with WBRT for radiographically persistent or progressive parenchymal disease after an HD-MTX–containing regimen. Overall survival (OS) was calculated from WBRT initiation using Kaplan–Meier (KM) with 95% confidence intervals. Planned subgroup analysis evaluated age (=50 vs. >50 years). For patients with available magnetic resonance imaging (MRI) post WBRT, cumulative incidence of CNS relapse following WBRT was calculated with death as a competing risk, and subgroup analysis based on WBRT dose was performed (<40 Gy BED10 vs. =40 Gy BED10). Best radiographic response was determined by review of post-treatment MRI reports. Relapse patterns and post-radiation systemic therapies were descriptively analyzed.
Results: 52 patients treated between 2007-2024 met inclusion criteria. Median age at WBRT was 59 years (range, 23–76), and median Karnofsky Performance Status at diagnosis was 80 (range, 40–100). Common dose-fractionation regimens included 45 Gy in 25 fractions (19%), 36 Gy in 20 fractions (17%), and 30 Gy in 10 fractions (10%); 27% received <40 Gy BED10. For the entire cohort, median follow-up among survivors was 42.8 months. Median OS was 17.5 months (95% CI, 9–51). Younger patients (=50 years) demonstrated improved OS compared to patients > 50 years (2-year OS 70% vs 37%, p=0.006).
Among 38 MRI-evaluable patients, radiographic response following WBRT included 25 complete responses, 7 partial responses, 2 stable disease, and 4 progressive disease. The risk of CNS relapse at 24 months was 49% (95% CI, 32–64), and there was no difference when comparing WBRT dose (p = 0.5). Durable disease control beyond 24 months was observed in 17 patients (45%), 15 of whom achieved a complete response. 10 of these patients received additional systemic therapy after WBRT, while 7 achieved durable control without further systemic therapy.Conclusion: Salvage WBRT produces high complete response rates and can achieve durable disease control in MTX-refractory PCNSL, with potential for meaningful survival particularly among younger patients. The absence of a clear dose–response relationship suggests opportunities to optimize dose-fractionation and explore pragmatic integration of lower dose WBRT with modern systemic therapies in prospective studies.