Clinicopathological and molecular characteristics of early-onset stage III colon adenocarcinoma: An analysis of 25 studies with 35,713 patients in the Adjuvant Colon Cancer End Points (ACCENT) database.

Authors

null

Zhaohui Jin

Division of Medical Oncology, Mayo Clinic, Rochester, MN

Zhaohui Jin , Jesse G. Dixon , Hiral Parekh , Frank A. Sinicrope , Greg Yothers , Daniel G. Haller , Hans Schmoll , Aimery De Gramont , Rachel Kerr , Julien Taieb , Eric Van Cutsem , Chris Twelves , Leonard B. Saltz , Naohiro Tomita , Takayuki Yoshino , Thierry Andre , Amit Mahipal , Richard M. Goldberg , Thomas J. George , Qian Shi

Organizations

Division of Medical Oncology, Mayo Clinic, Rochester, MN, Department of Health Science Research, Mayo Clinic, Rochester, MN, Cancer Specialist of North Florida, Jacksonville, FL, Mayo Clinic, Rochester, MN, University of Pittsburgh Department of Biostatistics, and NRG Oncology Statistics and Data Management Center, Pittsburgh, PA, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, Martin Luther University, Halle, Germany, Franco-British Institute, Levallois-Perret, France, University of Oxford, Oxford, United Kingdom, Hôpital Européen Georges Pompidou, Paris, France, University Hospitals Gasthuisberg, Leuven and KU Leuven, Leuven, Belgium, St. James's Hospital and The University of Leeds, Leeds, United Kingdom, Department of Colorectal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan, National Cancer Center Hospital East, Kashiwa, Japan, Sorbonne Université and Hôpital-Saint Antoine, Paris, France, West Virginia University Cancer Institute, Morgantown, WV, University of Florida/UF Health Cancer Center, Gainesville, FL

Research Funding

No funding received
None

Background: Colon cancer (CC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (20-49 years) is increasing. There are limited data suggesting that, as a group, patients with early onset CRC (eoCC) may have different phenotypic characteristics compared to those with late onset CRC (loCC, age ≥ 50 years). Methods: Individual patient data on 35,713 subjects with stage III CC from 25 randomized studies (recruiting between 1987 and 2009) in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for gender, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness and molecular markers. Results: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III eoCC (n = 6246) had similar distributions according to gender, race, PS, risk group, tumor sidedness and T/N stage compared to those with loCC (n = 29467). Patients with eoCC were significantly less likely to be overweight (30.2% vs 36.2%) but more commonly had ≥ 12 lymph nodes resected (69.5% vs 58.7%). The eoCC 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 frequency of Lynch syndrome in eoCC. In univariate analysis, patients with stage III eoCC had significantly better OS, DFS, and SAR; the difference between 3-year DFS and RFR strongly suggests the OS/DFS difference between these the eoCC and loCC may be due to increased competing risks and comorbidities in patients with loCC. In multivariate analysis, age at onset lost its prognostic value when outcome was adjusted for molecular markers. The clear relation between age of onset and KRAS/BRAF status was confirmed in the interaction analysis. Conclusions: Tumor biology was an important determinant of prognosis regardless of patient age. In multivariate analysis age of onset was not a statistically significant determinant of outcome.


eoCC
loCC
Univariate Analysis
Multivariate analysis with molecular markers
Hazard Ratio
95% CI
Adjusted Hazard Ratio
95% CI
5-y OS,%
76.0
71.6
0.80
0.76-0.85**
0.92
0.80-1.05
3-y DFS, %
69.4
68.2
0.89
0.85-0.93**
0.94
0.83-1.06
3-y RFR, %
70.2
70.4
1.00
0.95-1.05
1.07
0.95-1.22
median SAR, months
20.4
17.5
0.85
0.80-0.90**
1.01
0.89-1.16

**p < 0.001.

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Colorectal and Anal

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer - Neo-Adjuvant/Adjuvant

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 3597)

DOI

10.1200/JCO.2021.39.15_suppl.3597

Abstract #

3597

Poster Bd #

Online Only

Abstract Disclosures

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