Lindsay A Renfro1, Axel Grothey2, Yuan Xue2, Leonard B Saltz2, Thierry André2, Chris Twelves2, Roberto Labianca2, Carmen J Allegra2, Steven R Alberts2, Charles L Loprinzi2, Greg Yothers2, Daniel J Sargent2. 1. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN (LAR, DJS); Department of Oncology, Mayo Clinic, Rochester, MN (AMG, SRA, CLL); Department of Statistics, University of Virginia, Charlottesville, VA (YX); Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (LBS); Hôpital Saint Antoine, Paris, France; Pierre and Marie Curie University, Paris, France (TA); Leeds Institute of Cancer and Pathology, University of Leeds and St. James's University Hospital, Leeds Cancer Research UK Centre, UK (CT); Oncology Unit, Ospedale Giovanni XXIII, Bergamo, Italy (RL); Division of Hematology and Oncology, University of Florida, Gainesville, FL (CJA); National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Pittsburgh, PA (GY). renfro.lindsay@mayo.edu. 2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN (LAR, DJS); Department of Oncology, Mayo Clinic, Rochester, MN (AMG, SRA, CLL); Department of Statistics, University of Virginia, Charlottesville, VA (YX); Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY (LBS); Hôpital Saint Antoine, Paris, France; Pierre and Marie Curie University, Paris, France (TA); Leeds Institute of Cancer and Pathology, University of Leeds and St. James's University Hospital, Leeds Cancer Research UK Centre, UK (CT); Oncology Unit, Ospedale Giovanni XXIII, Bergamo, Italy (RL); Division of Hematology and Oncology, University of Florida, Gainesville, FL (CJA); National Surgical Adjuvant Breast and Bowel Project Biostatistical Center, Pittsburgh, PA (GY).
Abstract
BACKGROUND: Current prognostic tools in colon cancer use relatively few patient characteristics. We constructed and validated clinical calculators for overall survival (OS) and time to recurrence (TTR) for stage III colon cancer and compared their performance against an existing tool (Numeracy) and American Joint Committee on Cancer (AJCC) version 7 staging. METHODS: Data from 15936 stage III patients accrued to phase III clinical trials since 1989 were used to construct Cox models for TTR and OS. Variables included age, sex, race, body mass index, performance status, tumor grade, tumor stage, ratio of positive lymph nodes to nodes examined, number and location of primary tumors, and adjuvant treatment (fluoropyrimidine single agent or in combination). Missing data were imputed, and final models internally validated for optimism-corrected calibration and discrimination and compared with AJCC. External validation and comparisons against Numeracy were performed using stage III patients from NSABP trial C-08. All statistical tests were two-sided. RESULTS: All variables were statistically and clinically significant for OS prediction, while age and race did not predict TTR. No meaningful interactions existed. Models for OS and TTR were well calibrated and associated with C-indices of 0.66 and 0.65, respectively, compared with C-indices of 0.58 and 0.59 for AJCC. These tools, available online, better predicted patient outcomes than Numeracy, both overall and within patient subgroups, in external validation. CONCLUSIONS: The proposed ACCENT calculators are internally and externally valid, better discriminate patient risk than AJCC version 7 staging, and better predict patient outcomes than Numeracy. These tools have replaced Numeracy for online clinical use and will aid prognostication and patient/physician communication.
BACKGROUND: Current prognostic tools in colon cancer use relatively few patient characteristics. We constructed and validated clinical calculators for overall survival (OS) and time to recurrence (TTR) for stage III colon cancer and compared their performance against an existing tool (Numeracy) and American Joint Committee on Cancer (AJCC) version 7 staging. METHODS: Data from 15936 stage III patients accrued to phase III clinical trials since 1989 were used to construct Cox models for TTR and OS. Variables included age, sex, race, body mass index, performance status, tumor grade, tumor stage, ratio of positive lymph nodes to nodes examined, number and location of primary tumors, and adjuvant treatment (fluoropyrimidine single agent or in combination). Missing data were imputed, and final models internally validated for optimism-corrected calibration and discrimination and compared with AJCC. External validation and comparisons against Numeracy were performed using stage III patients from NSABP trial C-08. All statistical tests were two-sided. RESULTS: All variables were statistically and clinically significant for OS prediction, while age and race did not predict TTR. No meaningful interactions existed. Models for OS and TTR were well calibrated and associated with C-indices of 0.66 and 0.65, respectively, compared with C-indices of 0.58 and 0.59 for AJCC. These tools, available online, better predicted patient outcomes than Numeracy, both overall and within patient subgroups, in external validation. CONCLUSIONS: The proposed ACCENT calculators are internally and externally valid, better discriminate patient risk than AJCC version 7 staging, and better predict patient outcomes than Numeracy. These tools have replaced Numeracy for online clinical use and will aid prognostication and patient/physician communication.
Authors: Hans-Joachim Schmoll; Thomas Cartwright; Josep Tabernero; Marek P Nowacki; Arie Figer; Jean Maroun; Timothy Price; Robert Lim; Eric Van Cutsem; Young-Suk Park; Joseph McKendrick; Claire Topham; Gemma Soler-Gonzalez; Filipo de Braud; Mark Hill; Florin Sirzén; Daniel G Haller Journal: J Clin Oncol Date: 2007-01-01 Impact factor: 44.544
Authors: Sharlene Gill; Charles Loprinzi; Hagen Kennecke; Axel Grothey; Garth Nelson; Ryan Woods; Caroline Speers; Steven R Alberts; Aditya Bardia; Michael J O'Connell; Daniel J Sargent Journal: Cancer Date: 2011-03-01 Impact factor: 6.860
Authors: Aimery de Gramont; Eric Van Cutsem; Hans-Joachim Schmoll; Josep Tabernero; Stephen Clarke; Malcolm J Moore; David Cunningham; Thomas H Cartwright; J Randolph Hecht; Fernando Rivera; Seock-Ah Im; György Bodoky; Ramon Salazar; Frédérique Maindrault-Goebel; Einat Shacham-Shmueli; Emilio Bajetta; Martina Makrutzki; Aijing Shang; Thierry André; Paulo M Hoff Journal: Lancet Oncol Date: 2012-11-16 Impact factor: 41.316
Authors: D Sargent; Q Shi; G Yothers; E Van Cutsem; J Cassidy; L Saltz; N Wolmark; B Bot; A Grothey; M Buyse; A de Gramont Journal: Eur J Cancer Date: 2011-01-21 Impact factor: 9.162
Authors: Daniel J Sargent; Harry S Wieand; Daniel G Haller; Richard Gray; Jacqueline K Benedetti; Marc Buyse; Roberto Labianca; Jean Francois Seitz; Christopher J O'Callaghan; Guido Francini; Axel Grothey; Michael O'Connell; Paul J Catalano; Charles D Blanke; David Kerr; Erin Green; Norman Wolmark; Thierry Andre; Richard M Goldberg; Aimery De Gramont Journal: J Clin Oncol Date: 2005-10-31 Impact factor: 44.544
Authors: Sharlene Gill; Charles L Loprinzi; Daniel J Sargent; Stephan D Thomé; Steven R Alberts; Daniel G Haller; Jacqueline Benedetti; Guido Francini; Lois E Shepherd; Jean Francois Seitz; Roberto Labianca; Wei Chen; Stephen S Cha; Michael P Heldebrant; Richard M Goldberg Journal: J Clin Oncol Date: 2004-04-05 Impact factor: 44.544
Authors: En Cheng; Fang-Shu Ou; Chao Ma; Donna Spiegelman; Sui Zhang; Xin Zhou; Tiffany M Bainter; Leonard B Saltz; Donna Niedzwiecki; Robert J Mayer; Renaud Whittom; Alexander Hantel; Al Benson; Daniel Atienza; Michael Messino; Hedy Kindler; Edward L Giovannucci; Erin L Van Blarigan; Justin C Brown; Kimmie Ng; Cary P Gross; Jeffrey A Meyerhardt; Charles S Fuchs Journal: J Clin Oncol Date: 2022-01-07 Impact factor: 44.544
Authors: Demetris Papamichael; Lindsay A Renfro; Christiana Matthaiou; Greg Yothers; Leonard Saltz; Katherine A Guthrie; Eric Van Cutsem; Hans-Joachim Schmoll; Roberto Labianca; Thierry André; Michael O'Connell; Steven R Alberts; Daniel G Haller; Panteleimon Kountourakis; Daniel J Sargent Journal: J Geriatr Oncol Date: 2016-07-25 Impact factor: 3.599
Authors: Alyson L Mahar; Carolyn Compton; Susan Halabi; Kenneth R Hess; Martin R Weiser; Patti A Groome Journal: J Surg Oncol Date: 2017-08-02 Impact factor: 3.454
Authors: Martin R Weiser; Meier Hsu; Philip S Bauer; William C Chapman; Iván A González; Deyali Chatterjee; Deepak Lingam; Matthew G Mutch; Ajaratu Keshinro; Jinru Shia; Efsevia Vakiani; Tsuyoshi Konishi; Yoshifumi Shimada; Zsofia Stadler; Neil H Segal; Andrea Cercek; Leonard Saltz; Rona Yaeger; Anna Varghese; Maria Widmar; Iris H Wei; Emmanouil P Pappou; J Joshua Smith; Garrett Nash; Philip Paty; Julio Garcia-Aguilar; Mithat Gonen Journal: J Clin Oncol Date: 2021-01-13 Impact factor: 44.544