title: Circulating Tumor DNA to Monitor Therapy for Aggressive B-Cell Lymphomas.
abstract: The goal of therapy for aggressive B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) is to achieve cure. Combination chemotherapy with rituximab cures most patients, but those with recurrent disease have a poor prognosis. Medical imaging scans such as computed tomography (CT) and positron emission tomography (PET) are the principal methods to assess response and monitor for disease relapse after therapy but are fundamentally limited by risks of radiation, cost, and a lack of tumor specificity. Novel sequencing-based DNA monitoring methods are capable of quantifying small amounts of circulating tumor DNA (ctDNA) before, during, and after therapy for mature B-cell lymphomas. Detection of ctDNA encoding clonal rearranged variable-diversity-joining (VDJ) receptor gene sequences has demonstrated improved analytical sensitivity and enhanced tumor specificity compared to imaging scans in DLBCL, offering broad clinical applicability across a range of aggressive B-cell lymphomas. Molecular monitoring of ctDNA has vaulted into the spotlight as a promising non-invasive tool with immediate clinical impact on monitoring for recurrence after therapy prior to clinical symptoms. As these clinical observations are validated, ctDNA monitoring needs to be investigated as a tool for response-adapted therapy and as a marker of minimal residual disease upon completion of therapy in aggressive B-cell lymphomas. Molecular monitoring of ctDNA holds tremendous promise that may ultimately transform our ability to monitor disease in aggressive B-cell lymphomas.
authors.affiliation: Hematology-Oncology Department, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 4954 N. Palmer Road, Bethesda, MD, 20889, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Kwok
authors.affiliation: Internal Medicine Department, Perlmutter Cancer Center, New York University Langone Medical Center, 560 E 34th Street, New York, NY, 10016, USA.
authors.forename: S Peter
authors.initials: SP
authors.lastname: Wu
authors.affiliation: Hematology-Oncology Department, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 4954 N. Palmer Road, Bethesda, MD, 20889, USA.
authors.forename: Clifton
authors.initials: C
authors.lastname: Mo
authors.affiliation: Pathology Department, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20895, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Summers
authors.affiliation: Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bldg 10, Room 4N/115, Bethesda, MD, 20892, USA. mark.roschewski@nih.gov.
authors.forename: Mark
authors.initials: M
authors.lastname: Roschewski
mesh_terms: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D003952:Diagnostic Imaging; D018450:Disease Progression; D005820:Genetic Testing / Q000379:methods / Q000592:standards; D023281:Genomics / Q000379:methods / Q000592:standards; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Circulating tumor DNA; Diffuse large B-cell lymphoma; Liquid biopsy; MRD; Minimal residual disease; Next-generation sequencing; Response-adapted; Surveillance imaging; VDJ