Rapid Diagnosis and Treatment Response Monitoring of Primary CNS Lymphoma Using CSF ctDNA Liquid Biopsy

The incidence of primary central nervous system lymphoma (PCNSL) has increased steadily, and the disease often progresses rapidly, with many patients presenting in critical condition. Timely biopsy and rapid pathological diagnosis are therefore essential for emergency management. However, biopsy is invasive and limited by bleeding risk, surgical contraindications, restricted tissue availability, and the effects of corticosteroid exposure or sampling location on pathological assessment. Moreover, delays inherent in imaging-based evaluation hinder the detection of very early relapse and may adversely affect patient outcomes.

The investigators have focused on precision diagnosis and treatment of PCNSL, established an emergency-to-pathology rapid-response system and provided preliminary evidence from a small cohort that cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) has distinctive value for diagnosis and treatment-response assessment. A key biomarker-based panel achieved 100% specificity and 85% sensitivity.

This project aims to establish a large, multicenter, disease-specific PCNSL database and characterize ctDNA alterations across more than 100 genes using ultra-deep sequencing. This project will integrate longitudinal CSF ctDNA profiles collected across disease stages with matched tissue-sequencing data. This approach will delineate the dynamic evolution of ctDNA molecular features and their spatiotemporal relationship with intratumoral heterogeneity. By developing multimodal AI models, the project aims to enable rapid early diagnosis, treatment-response prediction, and longitudinal disease monitoring, while elucidating mechanisms of therapeutic resistance and ultimately improving patient outcomes.