학술논문

Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas.
Document Type
Article
Source
Cancers. Jan2024, Vol. 16 Issue 2, p321. 17p.
Subject
*NUCLEIC acid analysis
*DNA analysis
*BIOMARKERS
*HODGKIN'S disease
*RESEARCH funding
*LACTATE dehydrogenase
*DESCRIPTIVE statistics
*EXTRACELLULAR space
*CELL lines
*DATA analysis software
*T-cell lymphoma
*NUCLEIC acids
*NON-Hodgkin's lymphoma
*BLOOD
BODY fluid examination
Language
ISSN
2072-6694
Abstract
Simple Summary: A liquid biopsy is a minimally invasive strategy that provides useful information for the management of cancer patients. Cell-free DNA (cfDNA) extraction and quantification could be easily integrated into standard care protocols. This study analyzes cfDNA concentration as a biomarker in 256 lymphoma cases, including unexplored subtypes. The findings reveal that all lymphoma subtypes release higher cfDNA levels than controls, and these levels correlate with subtype, aggressiveness, and prognostic markers like the International Prognostic Index (IPI) and Ann Arbor Stage. Additionally, the study includes 49 large B-cell lymphomas (LBCL) cases, in which pre- and post-treatment levels of cfDNA were assessed, demonstrating that cfDNA dynamics correlate with treatment response and can, in some cases, improve PET-based response assessment. The study also includes NGS genetic characterization in tissue and cfDNA in a subgroup of LBCL. Overall, the study highlights cfDNA's potential as a biomarker for lymphoma management, enabling its integration in the near future into routine clinical practice. Background: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. Methods: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. Results: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. Conclusions: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients. [ABSTRACT FROM AUTHOR]