Outcomes and Failure Patterns for >500 Patients Treated for Primary CNS Lymphoma: Exploring Modern Roles for Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Given concerns for neurotoxicity of standard dose (SD) whole brain radiotherapy (WBRT) after high-dose methotrexate (MTX), consolidation for primary CNS lymphoma (PCNSL) has evolved to either autologous stem-cell transplant (ASCT) or reduced dose (RD; <24Gy) WBRT. We analyzed outcomes and failure patterns by consolidation strategy in the largest cohort of contemporarily treated patients. <h3>Materials/Methods</h3> PCNSL patients treated from 1983-2020 were analyzed. Initial T1 post-contrast-enhancing disease was characterized by site. Patients were stratified by response (complete [CR], partial [PR], stable, progression) to induction and consolidation (ASCT, RD vs SD WBRT, cytarabine, other). Site of initial progression was characterized as local (involving/adjacent to initial site) vs distant intraparenchymal, leptomeningeal (CSF and/or MRI), or other. Progression-free survival (PFS) was assessed from diagnosis using Kaplan Meier and proportional hazards. Logistic regression was used to evaluate associations with local failure. <h3>Results</h3> Of 645 patients, 564 were eligible (diffuse large B-cell, sufficient data, ≥1 MRI response assessment). Median follow-up was 2.7 years (IQR 1.2-5.6). Median age was 63 (range 19-90), and most (57%) were recursive partitioning analysis (RPA) class 2 (age≥50, KPS≥70). Most had supratentorial (423, 81%), multifocal (276, 54%), bilateral (225, 43%), and deep structure involvement (310, 56%). Most received MTX-based induction (536, 95%); common regimens were rituximab, MTX, procarbazine, vincristine (R-MVP; 253, 45%) and MVP (144, 26%). Most (412, 73%) responded to induction (225 CR, 187 PR). 385 patients were consolidated: 116 (30%) WBRT, of which 55 (47%) had RD; 81 (21%) ASCT; 175 (45%) cytarabine; 13 (3%) other. Consolidation approach changed over time (SD WBRT earlier vs RD WBRT and ASCT recently). RPA differed by consolidation (93% of ASCT vs 75% of RD WBRT had RPA 1-2; chi square p=0.02). Of those consolidated, 344 (89%) achieved CR, of whom 141 (41%) later relapsed, mostly non-locally (132, 94%) without maintaining laterality or focality. Early progression on induction or consolidation was more likely local compared to later relapses (OR 12.9 95%CI 6.4-25.9; p<0.001). Median PFS among those with CR was 4.9 years (95%CI 3.6-6.0) and differed by consolidation (log-rank p<0.001): ASCT 9.8 years (95%CI 7.5-NR); RD WBRT 7.6 years (95%CI 4.4-13.2); SD WBRT 4.2 years (95%CI 2.7-7.4); cytarabine 2.8 years (95%CI 2.2-3.7). Among those with RPA 1-2, there was no PFS difference between ASCT and RD WBRT (HR 0.74 95%CI 0.38-1.43). <h3>Conclusion</h3> In a large PCNSL cohort, modern consolidation (ASCT, RD WBRT) had similarly improved PFS vs SD WBRT or no RT. Performance status and age influenced consolidation strategy and outcomes, suggesting a role for further personalization. Early progression patterns may reveal a role for focal RT for residual disease. Future analyses will focus on the relationship between consolidation strategy and failure patterns.