AB080. High-dose methotrexate with and without intra-thecal methotrexate and whole-brain radiotherapy for primary central nervous system lymphoma: a systematic review.

Background: Primary central nervous system lymphoma (PCNSL) requires effective & well-tolerated treatment strategies. The use of high-dose methotrexate (HD-MT) with or without intra-thecal methotrexate (IT-MT) and whole-brain radiotherapy (WBRT) has emerged as a prominent approach for PCNSL. This systematic review aims to assess the efficacy and safety of these treatment modalities.

Methods: A comprehensive search strategy identified relevant studies from PubMed, EMBASE, and Cochrane Library. The following search terms were used: "high-dose methotrexate", "primary central nervous system lymphoma", "intra-thecal methotrexate", and "whole-brain radiotherapy". We included randomized controlled trials (RCTs), cohort studies & case-controlled studies evaluating the use of HD-MT with or without IT-MT and whole-brain radiotherapy in the treatment of confirmed PCNSL. Data extraction & quality assessment was conducted by two independent reviewers. Primary outcomes include overall survival (OS), progression-free survival (PFS) & treatment-related adverse events (TRAEs). Secondary outcomes were neurological function and quality of life (QOL) assessments. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Newcastle-Ottawa Scale for observational studies.

Results: We identified 5 studies, consisting of 1 RCT, 3 cohort studies, and 1 case-controlled study. Pooled analysis revealed that HD-MT with or without IT-MT and whole-brain radiotherapy significantly improved both OS and PFS compared to other treatment modalities but we found no significant difference between patients who received HD-MT with or without IT-MT. Combination therapy was generally well-tolerated, with manageable TRAE. Subgroup analyses stratified by age, disease stage, and other relevant factors demonstrated consistent efficacy and safety profiles across different patient populations. The risk of bias assessment indicated that the majority of the included studies had low-moderate risk of bias.

Conclusions: There was no significant difference between patients who received HD-MT with or without IT-MT plus radiotherapy, emphasizing the comparable efficacy of these treatment modalities. Combination therapy was generally well-tolerated, with manageable TRAE. This highlights the favourable safety profile of HD-MT with fewer side effects compared with the combination of IT-MT.