Patterns of Treatment Failure in Primary Central Nervous System Lymphoma

Objectives: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement. Methods: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure. Results: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P=0.02), KPS (HR: 0.10, P=0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P<0.01), and use of intrathecal chemotherapy (HR: 0.03, P<0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P=0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT (P=0.37), Rituximab (P=0.12), or attempted gross total resection (P=0.72). Conclusions: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.