Table 2 Study weaknesses and strategies for clinical implementation of cfDNA analysis in CNS lymphoma

High rate of CSF samples with insufficient cfDNA level (≈ 30%)

Increase CSF collection volume to at least 20 mL to enhance the success rate of ctDNA analysis and overall sensitivity.

Restricted plasma utility for CNS lymphoma diagnostics

Prioritize CSF as the preferred source for ctDNA analysis in routine setting, providing higher diagnostic accuracy.

Lack of longitudinal sampling for CSF-ctDNA monitoring

Implement ultra-sensitive methodologies in prospective studies to improve early CNS relapse detection and assess clinical utility.

Small cohort size limiting correlation with clinical outcomes

Conduct larger multi-center studies to validate the prognostic and predictive value of cfDNA analysis in CNS lymphoma.