Potential of Circulating Tumor DNA for the Management of Patients With Lymphoma

The characterization of circulating tumor-derived DNA (ctDNA) has recently emerged in the field of oncology as a powerful method to identify tumor-specific genetic aberrations using peripheral blood testing. Several technical precautions are needed at the pre-analytic stage (given the short half-life of free nucleic acids in plasma), and numerous techniques-with different sensitivities-are available to identify these molecular aberrations, ranging from the detection of single point mutations to extended genetic screening panels. Although a "liquid biopsy" cannot be substituted for the pathological examination of tissue specimens for diagnostic purposes, it can sometimes complement pathology results or serve as a proxy approach for particular lymphoma presentations where biopsies are sometimes difficult to perform. Moreover, ctDNA testing can characterize, at diagnosis or during treatment, mutations that may contribute to the choice of an optimal targeted therapy (such as Bruton tyrosine kinase or EZH2 inhibitors) or detect the emergence of resistance to those therapies. High levels of ctDNA before treatment appear to be correlated with advanced disease stages and prognosis in diffuse large B-cell and follicular lymphomas. Real-time follow-up of ctDNA levels during therapy in several lymphoma subtypes (diffuse large B-cell and Hodgkin lymphomas) has been explored: preliminary studies have demonstrated that this monitoring technique can predict clinical outcomes (end of treatment response and risk of progression after treatment completion) and that this approach may complement the information provided by metabolic imaging assessments. Technical standardization and careful prospective evaluation of the role of ctDNA monitoring in clinical studies represent current important challenges to allowing its application in routine practice.