Liquid Biopsy in Early Colorectal Lesions

Official title

Biobank for Validating Liquid Biopsy in Predicting the Prognosis of Superficial Colonic Lesions

Overview

Early colorectal cancer screening increasingly detects small superficial colonic lesions, but current diagnostic tools still struggle to distinguish benign from malignant lesions and to assess lymph node risk. As histology after resection has limited accuracy, many patients undergo unnecessary surgery. Liquid biopsy, analyzing circulating biomarkers such as tumor DNA, extracellular vesicles, and nucleosomes, offers a non-invasive way to better classify these lesions. Emerging evidence suggests it may outperform current criteria for predicting lymph node involvement in T1 colorectal cancer. This study will establish a biobank of 1,000 patients to identify blood-based signatures that predict tumor stage and lymph node status. The hypothesis of the study is that circulating biomarkers can accurately differentiate benign from malignant lesions and identify patients with or without lymph node metastasis.

Detailed description

Introduction :

Early colorectal cancer screening increasingly identifies superficial colonic lesions, but current diagnostic tools often fail to accurately distinguish benign from malignant lesions or to predict lymph node involvement. As histological criteria have limited predictive value, many patients with T1 tumors undergo unnecessary surgery. Liquid biopsy, based on circulating blood biomarkers, offers a promising non-invasive alternative that may improve diagnostic precision.

Aim :

The study aims to build a biobank of 1,000 patients with superficial colonic tumors to identify and validate circulating biomarker signatures capable of predicting tumor malignancy and lymph node status. The hypothesis is that liquid biopsy markers can reliably differentiate benign from malignant lesions and identify patients at risk of lymph node metastasis.

Methods :

This is a multicenter prospective cohort study embedded in the FECCo cohort. Blood samples will be collected at the time of endoscopic resection and, for pT1 lesions, again 2-6 weeks later. Clinical data will be retrieved annually from the FECCo database. Diagnostic performance of circulating biomarkers will be assessed using ROC curves, logistic regression (Lasso), and bootstrap validation to identify signatures associated with malignancy and lymph node involvement.

Interventions

• Other Venous blood sampling
  Five 6-7 ml EDTA tubes of venous blood will be collected at two points during the care pathway: * Immediately before the endoscopic procedure, at the time of catheter insertion for general anesthesia. This is to study the signal intensity at a baseline stage. * Between 2 and 6 weeks after submucosal dissection (only in cases of pT1 adenocarcinoma) and before any further surgery for pT1 cancer. This is to study the presence or absence of a residual signal after local resection.

Primary outcome measures

• Extracellular vesicles (EVs) [Time frame: Morning of endoscopic resection (Day 0), 2 and 6 weeks after Day 0 (only for pT1 tumor)]

Secondary outcome measures (3)

• Circulating nucleosomes [Time frame: Morning of endoscopic resection (Day 0), 2 and 6 weeks after Day 0 (only for pT1 tumor)]
• Circulating tumor DNA (ctDNA) [Time frame: Morning of endoscopic resection (Day 0), 2 and 6 weeks after Day 0 (only for pT1 tumor)]
• Circulating proteomic profile via O-link technology [Time frame: Morning of endoscopic resection (Day 0), 2 and 6 weeks after Day 0 (only for pT1 tumor)]

Eligibility criteria

Inclusion criteria

• Patient of legal age (≥ 18 years)
• Patient with a superficial colonic tumor refered for submucosal dissection
• Patient included in the FECCo cohort (patients will be included concomitantly in FECCO-Biobank)
• Patient wishing to participate in the FECCO-BioBank biological collection

Exclusion criteria

• Person with significant comorbidities preventing blood sampling
• Patients with a distant metastasis detected by imaging
• Person unable to read and write French
• Person who have expressed their opposition to participating in this research after being informed by an investigator and having read the information sheet
• Person not benefiting from a national health insurance scheme
• Person under legal protection, guardianship or curatorship
• Person participating in other study with an ongoing exclusion period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 12 centers

• University Hospital of Amiens — Amiens
• University Hospital of Bordeaux — Bordeaux
• University Hospital of Brest — Brest
• University Hospital of Dijon — Dijon
• University Hospital of Limoges — Limoges
• Civil Hospices of Lyon — Lyon
• Jean Mermoy Private Hospital — Lyon
• University Hospital of Montpellier — Montpellier
• … and 4 more centers

Publications

• Lecomte T, Tougeron D, Chautard R, Bressand D, Bibeau F, Blanc B, Cohen R, Jacques J, Lagasse JP, Laurent-Puig P, Lepage C, Lucidarme O, Martin-Babau J, Panis Y, Portales F, Taieb J, Aparicio T, Bouche O; Thesaurus National de Cancerologie Digestive (TNCD); Societe Nationale Francaise de Gastroenterologie (SNFGE); Federation Francophone de Cancerologie Digestive (FFCD); Groupe Cooperateur multidis PMID 38383162
• Zwager LW, Bastiaansen BAJ, Montazeri NSM, Hompes R, Barresi V, Ichimasa K, Kawachi H, Machado I, Masaki T, Sheng W, Tanaka S, Togashi K, Yasue C, Fockens P, Moons LMG, Dekker E. Deep Submucosal Invasion Is Not an Independent Risk Factor for Lymph Node Metastasis in T1 Colorectal Cancer: A Meta-Analysis. Gastroenterology. 2022 Jul;163(1):174-189. doi: 10.1053/j.gastro.2022.04.010. Epub 2022 Apr 15 PMID 35436498
• Alix-Panabieres C, Pantel K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov. 2021 Apr;11(4):858-873. doi: 10.1158/2159-8290.CD-20-1311. PMID 33811121
• Chung DC, Gray DM 2nd, Singh H, Issaka RB, Raymond VM, Eagle C, Hu S, Chudova DI, Talasaz A, Greenson JK, Sinicrope FA, Gupta S, Grady WM. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714. PMID 38477985
• Wada Y, Shimada M, Murano T, Takamaru H, Morine Y, Ikemoto T, Saito Y, Balaguer F, Bujanda L, Pellise M, Kato K, Saito Y, Ikematsu H, Goel A. A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer. Gastroenterology. 2021 Jul;161(1):151-162.e1. doi: 10.1053/j.gastro.2021.03.062. Epub 2021 Apr 2. PMID 33819484
• Miyazaki K, Wada Y, Okuno K, Murano T, Morine Y, Ikemoto T, Saito Y, Ikematsu H, Kinugasa Y, Shimada M, Goel A. An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer. Mol Cancer. 2023 Jan 6;22(1):2. doi: 10.1186/s12943-022-01685-8. PMID 36609320
• Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Flejou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H. The Vienna classification of gastroint PMID 10896917

Identifiers

NCT: NCT07319104 · RECHMPL25_0092 · 2025-A02328-41

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗