Radiotherapy in primary central nervous system lymphoma: Evolution of its role and current position in combined...

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal lymphoma. Whole-brain radiotherapy (WBRT) historically served as the therapeutic backbone, but its use has declined because of substantial delayed neurocognitive toxicity. The treatment paradigm shifted with the adoption of high-dose methotrexate (HD-MTX)-based chemotherapy as first-line therapy, and high-dose chemotherapy followed by autologous stem-cell transplantation (HDC-ASCT) has since emerged as an effective consolidation strategy that can achieve disease control comparable to WBRT while reducing the risk of long-term neurotoxicity. This review traces the evolution of radiotherapy in PCNSL from primary monotherapy to a precision modality within modern multimodal strategies. We critically appraise key issues, including the timing of radiotherapy, reduced-dose WBRT (rd-WBRT), involved-field approaches, hippocampal avoidance, controversies surrounding orbital irradiation, and the use of advanced radiotherapy techniques to optimize tumor control while minimizing late sequelae. We also examine radiotherapy combined with novel systemic agents, highlighting mechanistic rationale and emerging clinical experience supporting its use as a bridging and consolidative modality alongside chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory disease. In addition, we compare disease characteristics and initial management across distinct lesion locations and summarize recent advances in radiomics and their translational potential in PCNSL. Collectively, this review positions radiotherapy as an indispensable yet increasingly selective, context-dependent component of contemporary PCNSL management.