Post-surgery sequelae unrelated to disease progression and chemotherapy revealed in follow-up of patients with stage III colon cancer.

BACKGROUND

We studied the poorly-known dynamics of circulating DNA (cir-nDNA), as monitored prospectively over an extended post-surgery period, in patients with cancer.

METHODS

On patients with stage III colon cancer (N = 120), using personalised molecular tags we carried out the prospective, multicenter, blinded cohort study of the post-surgery serial analysis of cir-nDNA concentration. 74 patients were included and 357 plasma samples tested.

FINDINGS

During post-operative follow-up, the patients' median cir-nDNA concentration was greater (P < 0.0001 in the [43-364 days range]) than both the median value in healthy individuals and the pre-surgery value. These cir-nDNA levels were highly associated with NETs markers (P-value associating MPO and cir-nDNA, and NE and cir-nDNA are 6.6 x 10

INTERPRETATION

(1), Given the inter-patient heterogeneity, the post-surgery cir-nDNA level cannot be considered a reliable value, and caution must be exercised when determining mutation allele frequency or the mutation status; and (2), specific studies must be undertaken to investigate the possible clinical impact of the persistent, low-grade inflammation resulting from elevated NETs levels, such as observed in these post-surgery patients, given that such levels are known to potentially induce adverse cardiovascular or thrombotic events.

FUNDING

This work was supported by the H2020 European ERA-NET grant on Translational Cancer Research (TRANSCAN-2).

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of interests TM has received personal fees from AMGEN, PIERRE FABRE, MSD, GALAPAGOS, SERVIER, MERCK SERONO and SANOFI, and TM declare participation on DSMB of the ongoing study PRODIGE 70 from FFCD, outside the submitted work. CICM has received personal fees from Instituto de Salud Carlos III/ISCIII and the Asociación Española Contra el Cancer/AECC, outside the submitted work. PXFC and CSV had received personal fees from Merck, Merck KGaA and Amgen, outside the submitted work. RSS is an advisor for GSK, Sanofi Genzyme and an expert testimonyEsteve, Laboratorios Servier, also has received personal fees from SACE Medhealth and WNT Pharma, outside the submitted work. AbB has received personal fees from Neophore, AstraZeneca Guardant Health, Kither Biotech and he is an advisor for Neophore, Roche/Genentech Global CRC, outside the submitted work. FdN has received personal fees from Illumina and Pierre Fabre, outside the submitted work. EF has received personal fees from Amgen and Pierre Fabre and Merck, outside the submitted work. MDM reports grants from GlaxoSmithKline, Exelixis, Roche, BeiGene, Novartis, Merck Sharp & Dohme, Pfizer; and he has received personal fees from Amgen, Merck, Ipsen, Viatris, Janssen, Astellas, AstraZeneca, Boehringer Ingelheim, Roche, Novartis, Servier, outside the submitted work. CM has received personal fees from Menarini, Roche, Veracyte, Illumina, Bayer and Daiichi Sakyo, outside the submitted work. AV reports grants from AVINCYTE, ROCHE and is an advisor for INCYTE, ROCHE, and BAYER, outside the submitted work. EE has received personal fees from Amgen, Bayer, Cure Teq, AG Hoffmann-La Roche, BMS, Boehringer Ingelheim, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Sanofi, Seagen, Servier and Takeda, outside the submitted work. NSG has received personal fees from AMGEN, MERCK, outside the submitted work, outside the submitted work. ART reports grants from SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553 and Société Française des Acides Nucléiques Circulants (SFAC), outside the submitted work. This does not alter our adherence to journal policies on sharing data and materials. All authors critically reviewed and approved the manuscript.