Clinical Predictors and Recurrence Characteristics Following Radiotherapy for Primary Central Nervous System Lymphoma: A Retrospective Cohort Study

<b>Background/Objectives</b>: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive tumor, primarily affecting elderly patients. Radiotherapy (RT) remains an important treatment option, particularly for patients who are ineligible for systemic chemotherapy. This study aims to identify prognostic factors and evaluate recurrence patterns in a real-world cohort of PCNSL patients treated with RT. <b>Methods</b>: We retrospectively analyzed 64 PCNSL patients treated with radiotherapy at our institution between 2000 and 2022. Clinical characteristics, treatment details, and outcomes were collected by chart review. Overall survival (OS) was analyzed using Kaplan-Meier and Cox regression methods. Recurrence patterns were assessed based on available post-treatment imaging. <b>Results</b>: Median patient age was 71 years (range: 31-83); 53.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Radiotherapy was used as first-line treatment in 62.5% of cases, primarily due to contraindications to chemotherapy. Median OS was 10 months from diagnosis. Age, poor performance status, seizures at presentation, absence of systemic therapy, incomplete radiotherapy, and <80% applied dose of planned radiotherapy were associated with inferior OS in our univariable analysis. Multivariable analysis confirmed age, systemic therapy, seizures, and radiotherapy dose <80% as independent predictors. Among twenty-nine patients with imaging follow-up, eight recurrences after RT were documented: six of those within, and two outside of the initially affected areas. All recurrences occurred within previously irradiated areas. <b>Conclusions</b>: This study confirms known negative prognostic factors in PCNSL and underscores the importance of systemic chemotherapy for curatively intended treatments aiming for prolonged survival. The recurrence patterns observed question the added benefit of whole-brain irradiation in preventing distant relapses. These findings support the need for prospective trials to optimize radiotherapy strategies while balancing efficacy and neurotoxicity.