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http://hdl.handle.net/2445/208092
Title: | Mutational Landscape and tumor burden assessed by cell-free DNA in Diffuse Large B-Cell Lymphoma in a population-based study |
Author: | Rivas Delgado, Alfredo Nadeu, Ferran Enjuanes, Anna Casanueva Eliceiry, Sebastián Mozas, Pablo Magnano, Laura Castrejón de Anta, Natalia Rovira, Jordina Dlouhy, I. Martín, Silvia Osuna, Miguel Rodríguez, Sonia Simó, Marc Pinyol, Magda Baumann, Tycho Beà Bobet, Sílvia M. Balagué Ponz, Olga Delgado, Julio (Delgado González) Villamor i Casas, Neus Setoain Perego, Xavier Campo Güerri, Elias Giné Soca, Eva López Guillermo, Armando |
Keywords: | Limfomes Càncer ADN Genètica mèdica Pronòstic mèdic Cèl·lules B Lymphomas Cancer DNA Medical genetics Prognosis B cells |
Issue Date: | 15-Jan-2021 |
Publisher: | American Association for Cancer Research |
Abstract: | Purpose: We analyzed the utility of cell-free DNA (cfDNA) in a prospective population-based cohort to determine the mutational profile, assess tumor burden, and estimate its impact in response rate and outcome in patients with diffuse large B-cell lymphoma (DLBCL). Experimental design: A total of 100 patients were diagnosed with DLBCL during the study period. Mutational status of 112 genes was studied in cfDNA by targeted next-generation sequencing. Paired formalin-fixed, paraffin-embedded samples and volumetric PET/CT were assessed when available. Results: Appropriate cfDNA to perform the analyses was obtained in 79 of 100 cases. At least one mutation could be detected in 69 of 79 cases (87%). The sensitivity of cfDNA to detect the mutations was 68% (95% confidence interval, 56.2-78.7). The mutational landscape found in cfDNA samples was highly consistent with that shown in the tissue and allowed genetic classification in 43% of the cases. A higher amount of circulating tumor DNA (ctDNA) significantly correlated with clinical parameters related to tumor burden (elevated lactate dehydrogenase and β2-microglobulin serum levels, advanced stage, and high-risk International Prognostic Index) and total metabolic tumor volume assessed by PET/CT. In patients treated with curative intent, high ctDNA levels (>2.5 log hGE/mL) were associated with lower complete response (65% vs. 96%; P < 0.004), shorter progression-free survival (65% vs. 85%; P = 0.038), and overall survival (73% vs. 100%; P = 0.007) at 2 years, although it did not maintain prognostic value in multivariate analyses. Conclusions: In a population-based prospective DLBCL series, cfDNA resulted as an alternative source to estimate tumor burden and to determine the tumor mutational profile and genetic classification, which have prognostic implications and may contribute to a future tailored treatment. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1158/1078-0432.ccr-20-2558 |
It is part of: | Clinical Cancer Research, 2021, vol. 27, num.2, p. 513-521 |
URI: | http://hdl.handle.net/2445/208092 |
Related resource: | https://doi.org/10.1158/1078-0432.ccr-20-2558 |
ISSN: | 1078-0432 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Fonaments Clínics) |
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