R Cohen1, Q Shi2, J Meyers2, Z Jin3, M Svrcek4, C Fuchs5, F Couture6, P Kuebler7, K K Ciombor8, J Bendell9, A De Jesus-Acosta10, P Kumar11, D Lewis12, B Tan13, M M Bertagnolli14, P Philip15, C Blanke16, E M O'Reilly17, A Shields15, J A Meyerhardt18. 1. Department of Health Science Research, Mayo Clinic, Rochester, USA; Sorbonne Université, Department of Medical Oncology, Saint-Antoine Hospital, Paris, France; Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France. Electronic address: romain.cohen@aphp.fr. 2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, USA. 3. Division of Oncology, Mayo Clinic and Mayo Comprehensive Cancer Center, Rochester, USA. 4. Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne Université, Department of Pathology, Saint-Antoine Hospital, Paris, France. 5. Genentech, South San Francisco, USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Yale School of Medicine, and Yale Cancer Center, New Haven, USA. 6. Hôtel-Dieu de Québec, Quebec, Canada. 7. Columbus NCI Community Clinical Oncology Research Program, Columbus, USA. 8. Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, USA. 9. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, USA. 10. Department of Medical Oncology, John Hopkins University, Baltimore, USA. 11. Illinois Cancercare, P.C., Peoria, USA. 12. Southeast Clinical Oncology Research, Cone Health Medical Group, Asheboro, USA. 13. Siteman Cancer Center, Washington University School of Medicine, St. Louis, USA. 14. Office of the Alliance Group Chair, Brigham and Women's Hospital, Boston, USA. 15. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, USA. 16. SWOG Cancer Research Network Group Chair's Office, Oregon Health and Science University Knight Cancer Institute, Portland, USA. 17. Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical Center, New York, USA. 18. Department of Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, USA.
Abstract
BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.
Authors: Axel Grothey; Alberto F Sobrero; Anthony F Shields; Takayuki Yoshino; James Paul; Julien Taieb; John Souglakos; Qian Shi; Rachel Kerr; Roberto Labianca; Jeffrey A Meyerhardt; Dewi Vernerey; Takeharu Yamanaka; Ioannis Boukovinas; Jeffrey P Meyers; Lindsay A Renfro; Donna Niedzwiecki; Toshiaki Watanabe; Valter Torri; Mark Saunders; Daniel J Sargent; Thierry Andre; Timothy Iveson Journal: N Engl J Med Date: 2018-03-29 Impact factor: 91.245
Authors: Nathalie Wong-Chong; Jill Motl; Grace Hwang; George J Nassif; Matthew R Albert; John R T Monson; Lawrence Lee Journal: Dis Colon Rectum Date: 2018-09 Impact factor: 4.585
Authors: M Bouquot; B Creavin; N Goasguen; N Chafai; E Tiret; T André; J-F Flejou; Y Parc; J H Lefevre; M Svrcek Journal: Colorectal Dis Date: 2018-06-30 Impact factor: 3.788
Authors: Jeffrey A Meyerhardt; Qian Shi; Charles S Fuchs; Jeffrey Meyer; Donna Niedzwiecki; Tyler Zemla; Priya Kumthekar; Katherine A Guthrie; Felix Couture; Philip Kuebler; Johanna C Bendell; Pankaj Kumar; Dequincy Lewis; Benjamin Tan; Monica Bertagnolli; Axel Grothey; Howard S Hochster; Richard M Goldberg; Alan Venook; Charles Blanke; Eileen M O'Reilly; Anthony F Shields Journal: JAMA Date: 2021-04-06 Impact factor: 56.272