3345 - Patterns of Intracranial Response and Relapse after Radiotherapy for Patients with Chemorefractory or Progressive Secondary CNS Lymphoma

G. Cederquist¹, K. R. Tringale², C. Hajj², Z. R. Moore³, H. G. Hubbeling⁴, A. Dreyfuss², B. Fregonese¹, L. Falchi³, M. Scordo⁵, C. Grommes⁶, J. Yahalom¹, and B. S. Imber²; ¹Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ³Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, ⁵Department of Medicine, Bone Marrow Transplant Division, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s):

Progressive secondary CNS lymphoma (SCNSL) after failure of CNS-directed systemic therapy is a challenging clinical entity with limited treatment options. Radiotherapy (RT) may be an effective salvage agent, but its role is not well defined. We sought to understand the response rates and patterns of intracranial failure after CNS RT for progressive SCNSL. Materials/

Methods:

We identified diffuse large B cell lymphoma (DLBCL) patients with SCNSL who received brain RT for progression after at least 1 line of SCNSL-directed therapy, defined as systemic therapy for active SCNSL as opposed to prophylaxis. Overall survival (OS) was calculated by Kaplan-Meier from RT start. RT response was evaluated with contrast MRI or CT using IPCG or RANO radiographic criteria for parenchymal or leptomeningeal disease (LMD), respectively. Risk of intracranial failure was calculated with death as a competing risk. Patterns of disease were defined as parenchymal-only versus diffuse (periventricular (PV) or radiographic LMD). Local failure was defined as disease progression at pre-RT lesion(s) only. Failure patterns were compared by fisher’s exact test.
Results:

Between 1999-2023, 55 patients received RT for progressive SCNSL. Median follow up was 3.5 months (m) (IQR, 1.5 – 8.8). 85% of patients had neurologic symptoms, 45% had extracranial disease. Patients received a median 2 lines of prior SCNSL-directed therapy (IQR, 1 - 3); 91% received a methotrexate (MTX)-based regimen with median 21 days (d) (IQR, 10 – 67) between last MTX and RT. Median RT dose was 30 Gy in 10 fractions delivered to whole brain (n = 44, 80%), partial brain (n = 9, 16%), or craniospinal axis (n = 2, 4%). Median OS was 3.5 m. 38 patients were evaluable for response. Overall response rate was 79%, complete response rate was 24%, and median time to best response 60 d (IQR, 30 – 145). 58% of patients were successfully bridged to subsequent therapy by a median 34 d post RT (IQR, 20 - 57). The 12 m risk of intracranial failure was 37% (95% CI, 19 – 57%) among patients who were bridged, and was 64% (95% CI, 30 – 85) among patients who were not bridged (p = 0.053). 19 patients had parenchymal-only disease (10 unifocal, 9 multifocal) with median largest lesion diameter 4.1 cm (range, 1.7 – 7.4). 19 patients had a diffuse pattern (12 PV, 7 LMD). 7 patients with parenchymal-only disease experienced intracranial failure, 5 of which were local. 8 patients with diffuse disease experienced intracranial failure, 1 of which was local (p = 0.035).
Conclusion:

SCNSL patients referred for RT were characterized by high-risk, symptomatic, treatment-resistant disease. CNS response rates to RT were high, though duration was limited. Most patients who were bridged to subsequent therapy maintained intracranial control at 12 m, suggesting that RT is best used as a bridging strategy or as palliation. Patients with parenchymal-only disease were enriched for local failure, suggesting the potential suitability of involved site partial brain RT, though further validation is needed.