Clinical applications of circulating tumor DNA in central nervous system lymphoma

Detection and characterization of circulating tumor DNA (ctDNA) in body fluids have the potential to revolutionize management of patients with lymphoma. Minimal access to malignant DNA through a simple blood draw or lumbar puncture is particularly appealing for CNS lymphomas (CNSL), which cannot be easily or repeatedly sampled without invasive surgeries. Profiling of ctDNA provides a real-time snapshot of the genetic composition in patients with CNSL and enables ultrasensitive quantification of lymphoma burden at any given time point during the course of the disease. Here, we broadly review technical challenges of ctDNA identification in CNSL, recent advances of innovative liquid biopsy technologies, potential clinical applications of ctDNA and how it may improve CNSL risk stratification, outcome prediction, and monitoring of measurable residual disease. Finally, we discuss clinical trials and scenarios in which ctDNA could be implemented to guide risk-adapted and personalized treatment decisions.