Applications of ctDNA in lymphoma. Schematic illustrates the potential applications of liquid biopsy assessment, as used for the identification of clinically actionable adverse-risk features in lymphomas at different disease milestones. A lymphoid tumor (left of vessel) is imagined as being accessible through blood plasma by analysis of ctDNA fragments. ctDNA is represented by purple double-stranded DNA molecules, and yellow double strands represent non–tumor-derived cell-free DNA molecules. The patient is evaluated by ctDNA profiling during various disease milestones over time (diagnosis, treatment, and relapse).488 During this temporal sequence, ctDNA can inform risk at diagnosis, during therapy, immediately after induction therapy, in surveillance of disease, and at progression or disease transformation,424 as illustrated in the panels associated with each milestone. At diagnosis, profiling of tumor DNA obtained from either tissue biopsies or noninvasively through genotyping of plasma (depicted as blood collection tubes),24 allows for the identification of patients with high tumor burden,246,421 histological subtypes,489 and prediction of outcomes.422 Assessment of ctDNA during and after lymphoma treatment facilitates the detection of both emerging resistance mutations and MRD before progression,419 with potential for noninvasive prediction of relapse and transformation.490 Tumor evolution in an anecdotal patient with DLBCL is illustrated, showing tumor response and clonal evolution over the course of the disease (detectable subclones at diagnosis are shown in blue/yellow; an emergent subclone after therapy is shown in red). EMR, early molecular response; MMR, major molecular response; TMTV, total metabolic tumor volume.
