Elisa Fontana1,2, Jeff Meyers3, Alberto Sobrero4, Timothy Iveson5, Anthony F Shields6, Julien Taieb7, Takayuki Yoshino8, Ioannis Souglakos9,10, Elizabeth C Smyth2,11, Florian Lordick2,12, Markus Moehler2,13, Anne Giraut14, Andrea Harkin15, Roberto Labianca16, Jeffrey Meyerhardt17, Thierry André18, Ioannis Boukovinas19, Sara Lonardi20, Mark Saunders21, Dewi Vernerey22,23, Eiji Oki24, Vassilis Georgoulias25, Irit Ben-Aharon2,26, Qian Shi3. 1. Sarah Cannon Research Institute UK, London, United Kingdom. 2. Gastrointestinal Tract Cancer Group, EORTC, Brussels, Belgium. 3. Department of Quantitative Health Science, Mayo Clinic, Rochester, MN. 4. Medical Oncology, Policlinico San Martino, Genova, Italy. 5. University of Southampton, Southampton, United Kingdom. 6. Karmanos Cancer Institute, Detroit, MI. 7. Université de Paris and Georges-Pompidou European Hospital, Paris, France. 8. National Cancer Center Hospital East, Chiba, Japan. 9. Laboratory of Translational Oncology, Faculty of Medicine, University of Crete, Crete, Greece. 10. Department of Medical Oncology, University Hospital of Heraklion, Iraklio, Greece. 11. Addenbrookes Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 12. Department of Medicine II, University Cancer Center Leipzig, Leipzig University Medical Center, Leipzig, Germany. 13. I. Department of Internal Medicine, University Medical Center Mainz, Mainz, Germany. 14. EORTC Headquarters, Brussels, Belgium. 15. CRUK Glasgow CTU, Institute of Cancer Sciences, University of Glasgow, United Kingdom. 16. Ospedale Papa Giovanni XXIII, Bergamo, Italy. 17. Dana-Farber Cancer Institute, Boston, MA. 18. Sorbonne Université and Hôpital Saint Antoine, Paris, France. 19. Bioclinic Thessaloniki, Thessaloniki, Greece. 20. Medical Oncology 3, Veneto Institute of Oncology IRCCS, Padua, Italy. 21. The Christie NHS Foundation Trust, Manchester, United Kingdom. 22. Methodology and Quality of Life Unit in Oncology, University Hospital of Besançon, Besançon, France. 23. INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University Bourgogne Franche-Comté, Besançon, France. 24. Kyushu University, Fukuoka, Japan. 25. Hellenic Oncology Research Group (HORG), Athens, Greece. 26. Division of Oncology, Rambam Health Care Center, Haifa, Israel.
Abstract
PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.
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