A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study.

LARC circulating tumor DNA (ctDNA) liquid biopsy next-generation sequencing rectal cancer (RC) watch and wait approach

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2022
Historique:
received: 21 03 2022
accepted: 23 05 2022
entrez: 15 7 2022
pubmed: 16 7 2022
medline: 16 7 2022
Statut: epublish

Résumé

Circulating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management. Twenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T We found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the T ctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.

Identifiants

pubmed: 35837093
doi: 10.3389/fonc.2022.900945
pmc: PMC9274270
doi:

Types de publication

Journal Article

Langues

eng

Pagination

900945

Informations de copyright

Copyright © 2022 Roesel, Epistolio, Molinari, Saletti, De Dosso, Valli, Franzetti-Pellanda, Deantonio, Biggiogero, Spina, Popeskou, Cristaudi, Mongelli, Mazzucchelli, Stefanini, Frattini and Christoforidis.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Oncol Rep. 2014 Mar;31(3):1466-72
pubmed: 24378613
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16368-73
pubmed: 16258065
Front Oncol. 2013 Oct 07;3:262
pubmed: 24109590
Clin Chem. 2015 Mar;61(3):514-22
pubmed: 25605683
Front Oncol. 2020 Jul 24;10:1028
pubmed: 32793464
J Clin Oncol. 2011 Dec 10;29(35):4633-40
pubmed: 22067400
J Gastrointest Surg. 2020 Aug;24(8):1880-1888
pubmed: 32314234
Ann Oncol. 2018 Mar 1;29(3):610-615
pubmed: 29253083
Clin Cancer Res. 2021 Jan 1;27(1):301-310
pubmed: 33046514
Sci Transl Med. 2020 Jun 17;12(548):
pubmed: 32554709
Arch Pathol Lab Med. 2017 Jun;141(6):751-758
pubmed: 28557599
JAMA Oncol. 2019 Aug 01;5(8):1124-1131
pubmed: 31070691
PLoS Med. 2021 Aug 31;18(8):e1003741
pubmed: 34464382
Hum Genomics. 2019 Aug 1;13(1):34
pubmed: 31370908
J Clin Oncol. 2014 Feb 20;32(6):579-86
pubmed: 24449238
Nat Rev Clin Oncol. 2020 Dec;17(12):757-770
pubmed: 32632268
Oncotarget. 2014 Oct 30;5(20):9641-9
pubmed: 25275295
Oncogene. 2016 May 5;35(18):2407-12
pubmed: 26257060
Gut. 2019 Apr;68(4):663-671
pubmed: 29420226
Lancet Oncol. 2016 Feb;17(2):174-183
pubmed: 26705854
Br J Cancer. 2020 Sep;123(5):803-810
pubmed: 32565539
Ann Surg. 2004 Oct;240(4):711-7; discussion 717-8
pubmed: 15383798
Lancet Oncol. 2010 Sep;11(9):835-44
pubmed: 20692872
Clin Transl Oncol. 2019 Jul;21(7):874-880
pubmed: 30506526
Haematologica. 2016 Jul;101(7):830-8
pubmed: 27102501
N Engl J Med. 2018 Nov 01;379(18):1754-1765
pubmed: 30380390
Colorectal Dis. 2012 May;14(5):567-71
pubmed: 21831177
Sci Transl Med. 2014 Feb 19;6(224):224ra24
pubmed: 24553385
CA Cancer J Clin. 2021 Mar;71(2):176-190
pubmed: 33165928
Immunotherapy. 2018 Sep;10(12):1023-1025
pubmed: 30185140
Acta Oncol. 2010 Apr;49(3):378-81
pubmed: 20151936
Lung Cancer. 2019 Nov;137:1-6
pubmed: 31518912
JAMA Oncol. 2019 Aug 1;5(8):1230-1231
pubmed: 31246247
Int J Mol Sci. 2019 Nov 28;20(23):
pubmed: 31795192
Oncotarget. 2015 Nov 10;6(35):38360-71
pubmed: 26451609
Lancet Oncol. 2015 Aug;16(8):919-27
pubmed: 26156652
Nat Med. 2008 Sep;14(9):985-90
pubmed: 18670422
JAMA Oncol. 2019 Apr 01;5(4):e185896
pubmed: 30629084
Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40
pubmed: 28881920
Cancer. 1994 Jun 1;73(11):2680-6
pubmed: 8194005
Clin Cancer Res. 1996 Oct;2(10):1665-71
pubmed: 9816114
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
PLoS One. 2014 Jan 30;9(1):e87966
pubmed: 24498230

Auteurs

Raffaello Roesel (R)

Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Samantha Epistolio (S)

Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.

Francesca Molinari (F)

Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.

Piercarlo Saletti (P)

Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland.
Medical Oncology Clinic, Clinica Luganese Moncucco, Lugano, Switzerland.
Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.

Sara De Dosso (S)

Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.
Istituto Oncologico della Svizzera Italiana, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

Mariacarla Valli (M)

Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

Alessandra Franzetti-Pellanda (A)

Service of Radiotherapy, Clinica Luganese Moncucco, Lugano, Switzerland.

Letizia Deantonio (L)

Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.
Radiation Oncology Clinic, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

Maira Biggiogero (M)

Clinical Research Unit, Clinica Luganese Moncucco, Lugano, Switzerland.

Paolo Spina (P)

Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.
Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.

Sotirios Georgios Popeskou (SG)

Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Alessandra Cristaudi (A)

Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Francesco Mongelli (F)

Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Luca Mazzucchelli (L)

Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.
Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.

Federico Mattia Stefanini (FM)

Faculty of Science and Technology-ESP, University of Milan, Milano, Italy.

Milo Frattini (M)

Istituto Cantonale di Patologia, Ente Ospedaliero Cantonale, Locarno, Switzerland.

Dimitri Christoforidis (D)

Department of Visceral Surgery, Regional Hospital of Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland.
Faculty of Biomedical Sciences, University of Southern Switzerland, Lugano, Switzerland.
Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland.

Classifications MeSH