Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study

Abstract Survivors of early-onset colorectal cancer (EOCRC, i.e., diagnosed before age 50) are likely to experience recurrence after completing treatment. In this international, multi-centric, phase I-II-III EDRN biomarker study, we identified a panel of tumor-derived biomarkers of EOCRC recurrence....

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Main Authors: Alessandro Mannucci, Goretti Hernández, Hiroyuki Uetake, Yasuhide Yamada, Francesc Balaguer, Hideo Baba, Tianhui Chen, Jinfei Chen, C. Richard Boland, Giulia Martina Cavestro, Enrique Quintero, Ajay Goel
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00978-7
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author Alessandro Mannucci
Goretti Hernández
Hiroyuki Uetake
Yasuhide Yamada
Francesc Balaguer
Hideo Baba
Tianhui Chen
Jinfei Chen
C. Richard Boland
Giulia Martina Cavestro
Enrique Quintero
Ajay Goel
author_facet Alessandro Mannucci
Goretti Hernández
Hiroyuki Uetake
Yasuhide Yamada
Francesc Balaguer
Hideo Baba
Tianhui Chen
Jinfei Chen
C. Richard Boland
Giulia Martina Cavestro
Enrique Quintero
Ajay Goel
author_sort Alessandro Mannucci
collection DOAJ
description Abstract Survivors of early-onset colorectal cancer (EOCRC, i.e., diagnosed before age 50) are likely to experience recurrence after completing treatment. In this international, multi-centric, phase I-II-III EDRN biomarker study, we identified a panel of tumor-derived biomarkers of EOCRC recurrence. We then trained and independently validated a machine learning model (XGBoost) to predict 5-year recurrence-free and overall survival (RFS and OS) of patients with stage I-III EOCRC. Patients with “low-risk” EOCRC demonstrated statistically higher rates of 2-, 5-, and 10 year RFS in both the training cohort (51.0 vs. 92.4%; 34.4% vs. 92.4%; 25.8% vs. 92.4%, respectively; p < 0.0001) and the validation cohort (78.9% vs. 100.0%; 75.0% vs. 100.0%; 75.0% vs. 100.0%, respectively; p = 0.0019). We also report a significant reduction in both over-treatment and missed recurrences compared to current clinically available options. This tissue-based, machine learning-powered assay was prognostic of long-term RFS and OS outcomes after curative-intent treatment of EOCRC (ENCORE was first registered on ClinicalTrial.gov [ID: NCT06271980] on February 15th, 2024).
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spelling doaj-art-c939c9e012d44b77be0466f76fd20d452025-08-20T03:22:46ZengNature Portfolionpj Precision Oncology2397-768X2025-06-019111110.1038/s41698-025-00978-7Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre studyAlessandro Mannucci0Goretti Hernández1Hiroyuki Uetake2Yasuhide Yamada3Francesc Balaguer4Hideo Baba5Tianhui Chen6Jinfei Chen7C. Richard Boland8Giulia Martina Cavestro9Enrique Quintero10Ajay Goel11Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of HopeGastroenterology Department, Hospital Universitario de Canarias, Universidad de La LagunaDepartment of Specialized Surgeries, Graduate School, Tokyo Medical and Dental UniversityDepartment of Gastrointestinal Medical Oncology, National Cancer Center HospitalGastroenterology Department, Hospital Clinic of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Institut d’ Investigacions Biomediques August Pi i Sunyer (IDIBAPS)Department of Gastroenterological Surgery, Graduate School of Life Sciences; Kumamoto UniversityDepartment of Cancer Prevention, Zhejiang Cancer HospitalDepartment of Oncology, the First Affiliated Hospital of Wenzhou Medical UniversityDivision of Gastroenterology, School of Medicine, University of California San DiegoGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University; IRCCS San Raffaele HospitalGastroenterology Department, Hospital Universitario de Canarias, Universidad de La LagunaDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of HopeAbstract Survivors of early-onset colorectal cancer (EOCRC, i.e., diagnosed before age 50) are likely to experience recurrence after completing treatment. In this international, multi-centric, phase I-II-III EDRN biomarker study, we identified a panel of tumor-derived biomarkers of EOCRC recurrence. We then trained and independently validated a machine learning model (XGBoost) to predict 5-year recurrence-free and overall survival (RFS and OS) of patients with stage I-III EOCRC. Patients with “low-risk” EOCRC demonstrated statistically higher rates of 2-, 5-, and 10 year RFS in both the training cohort (51.0 vs. 92.4%; 34.4% vs. 92.4%; 25.8% vs. 92.4%, respectively; p < 0.0001) and the validation cohort (78.9% vs. 100.0%; 75.0% vs. 100.0%; 75.0% vs. 100.0%, respectively; p = 0.0019). We also report a significant reduction in both over-treatment and missed recurrences compared to current clinically available options. This tissue-based, machine learning-powered assay was prognostic of long-term RFS and OS outcomes after curative-intent treatment of EOCRC (ENCORE was first registered on ClinicalTrial.gov [ID: NCT06271980] on February 15th, 2024).https://doi.org/10.1038/s41698-025-00978-7
spellingShingle Alessandro Mannucci
Goretti Hernández
Hiroyuki Uetake
Yasuhide Yamada
Francesc Balaguer
Hideo Baba
Tianhui Chen
Jinfei Chen
C. Richard Boland
Giulia Martina Cavestro
Enrique Quintero
Ajay Goel
Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
npj Precision Oncology
title Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
title_full Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
title_fullStr Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
title_full_unstemmed Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
title_short Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study
title_sort prediction of long term recurrence free and overall survival in early onset colorectal cancer the encore multi centre study
url https://doi.org/10.1038/s41698-025-00978-7
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