American Association for Cancer Research
10780432ccr202558-sup-246337_3_supp_6654320_qrrzrd.docx (7.14 MB)

Supplemental Material from Mutational Landscape and Tumor Burden Assessed by Cell-free DNA in Diffuse Large B-Cell Lymphoma in a Population-Based Study

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journal contribution
posted on 2023-03-31, 22:21 authored by Alfredo Rivas-Delgado, Ferran Nadeu, Anna Enjuanes, Sebastián Casanueva-Eliceiry, Pablo Mozas, Laura Magnano, Natalia Castrejón de Anta, Jordina Rovira, Ivan Dlouhy, Silvia Martín, Miguel Osuna, Sonia Rodríguez, Marc Simó, Magda Pinyol, Tycho Baumann, Silvia Beà, Olga Balagué, Julio Delgado, Neus Villamor, Xavier Setoain, Elías Campo, Eva Giné, Armando López-Guillermo

Suppplementary Methods and Figures


Ministerio de Ciencia e Innovación

European Regional Development Fund


Generalitat de Catalunya

Canadian Institutes of Health Research



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). 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. 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. 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.