Zhaohui Jin1, Jesse G Dixon2, Jack M Fiskum2, Hiral D Parekh3, Frank A Sinicrope1, Greg Yothers4, Carmen J Allegra5, Norman Wolmark6, Daniel Haller7, Hans-Joachim Schmoll8, Aimery de Gramont9, Rachel Kerr10, Julien Taieb11, Eric Van Cutsem12, Christopher Tweleves13, Michael O'Connell1, Leonard B Saltz1, Sotaro Sadahiro14, Charles D Blanke15, Naohiro Tomita16, Jean-Francois Seitz17, Charles Erlichman1, Takayuki Yoshino18, Takeharu Yamanaka19, Silvia Marsoni20, Thierry Andre21, Amit Mahipal1, Richard M Goldberg22, Thomas J George23, Qian Shi2. 1. Department of Oncology, Mayo Clinic, Rochester, MN, USA. 2. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. 3. Cancer Specialists of North Florida, Jacksonville, FL, USA. 4. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. 5. Department of Medicine, Shands Cancer Center, University of Florida, Gainesville, FL, USA. 6. University of Pittsburgh, Pittsburgh, PA, USA. 7. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 8. Department of Internal Medicine IV-Hematology-Oncology, University Clinic Halle (Saale), Martin-Luther-University Halle-Wittenberg, Halle, Germany. 9. Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France. 10. University of Oxford, Oxford, UK. 11. Sorbonne Paris Cité, Paris Descartes University Georges Pompidou European Hospital, Paris, France. 12. Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. 13. University of Leeds and St. James's Institute of Oncology, Tom Connors Cancer Research Center, University of Bradford, Bradford, UK. 14. Department of Surgery, Tokai University, Tokyo, Japan. 15. Oregon Health and Science University, Portland, OR, USA. 16. Cancer Treatment Center, Toyonaka Municipal Hospital, Toyonaka, Japan. 17. Hôpital La Timone, Marseille, France. 18. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 19. Department of Biostatistics, Yokohama City University School of Medicine, Kanagawa, Japan. 20. FIRC Institute of Molecular Oncology, Milan, Italy. 21. Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. 22. West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center, Morgantown, WV, USA. 23. University of Florida, Health Cancer Center, Gainesville, FL, USA.
Abstract
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.
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.
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