Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database.


Journal

Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089

Informations de publication

Date de publication:
29 11 2021
Historique:
received: 28 12 2020
revised: 23 03 2021
accepted: 21 06 2021
pubmed: 19 8 2021
medline: 22 11 2022
entrez: 18 8 2021
Statut: ppublish

Résumé

Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers. Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

Sections du résumé

BACKGROUND
Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing.
METHODS
Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided.
RESULTS
Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers.
CONCLUSION
Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.

Identifiants

pubmed: 34405233
pii: 6353731
doi: 10.1093/jnci/djab123
pmc: PMC8634466
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1693-1704

Subventions

Organisme : NCI NIH HHS
ID : UG1 CA233290
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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Auteurs

Zhaohui Jin (Z)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Jesse G Dixon (JG)

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Jack M Fiskum (JM)

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Hiral D Parekh (HD)

Cancer Specialists of North Florida, Jacksonville, FL, USA.

Frank A Sinicrope (FA)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Greg Yothers (G)

Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.

Carmen J Allegra (CJ)

Department of Medicine, Shands Cancer Center, University of Florida, Gainesville, FL, USA.

Norman Wolmark (N)

University of Pittsburgh, Pittsburgh, PA, USA.

Daniel Haller (D)

Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Hans-Joachim Schmoll (HJ)

Department of Internal Medicine IV-Hematology-Oncology, University Clinic Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle, Germany.

Aimery de Gramont (A)

Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France.

Rachel Kerr (R)

University of Oxford, Oxford, UK.

Julien Taieb (J)

Sorbonne Paris Cité, Paris Descartes University Georges Pompidou European Hospital, Paris, France.

Eric Van Cutsem (E)

Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.

Christopher Tweleves (C)

University of Leeds and St. James's Institute of Oncology, Tom Connors Cancer Research Center, University of Bradford, Bradford, UK.

Michael O'Connell (M)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Leonard B Saltz (LB)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Sotaro Sadahiro (S)

Department of Surgery, Tokai University, Tokyo, Japan.

Charles D Blanke (CD)

Oregon Health and Science University, Portland, OR, USA.

Naohiro Tomita (N)

Cancer Treatment Center, Toyonaka Municipal Hospital, Toyonaka, Japan.

Jean-Francois Seitz (JF)

Hôpital La Timone, Marseille, France.

Charles Erlichman (C)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Takayuki Yoshino (T)

Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Takeharu Yamanaka (T)

Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan.

Silvia Marsoni (S)

FIRC Institute of Molecular Oncology, Milan, Italy.

Thierry Andre (T)

Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.

Amit Mahipal (A)

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Richard M Goldberg (RM)

West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center, Morgantown, WV, USA.

Thomas J George (TJ)

University of Florida, Health Cancer Center, Gainesville, FL, USA.

Qian Shi (Q)

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

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