BACKGROUND: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood. METHODS: One-hundred ten consecutive patients with metastatic colorectal adenocarcinoma underwent testing for KRAS exon 2 mutations by polymerase chain reaction amplification and direct nucleotide sequencing. The clinical characteristics, treatments, and outcomes of these patients were then analyzed retrospectively, stratified according to whether patients presented with synchronous or metachronous metastasis and according to KRAS mutation status (WT or mutated). RESULTS: For the entire cohort, the median overall survival from the date of diagnosis of metastatic disease was 34.3 months (95% confidence interval, 28.3-49.4 months) for patients with WT KRAS (n = 70). The median overall survival for patients with mutated KRAS (n = 40) was 40.3 months (95% confidence interval, 27.9-51.1 months; log-rank P = .91). Kaplan-Meier survival analysis indicated that 3-year overall survival and 5-year overall survival were not statistically different. Within the subgroups of patients with synchronous and metachronous metastatic disease, no significant differences were observed in median overall survival, 3-year overall survival, or 5-year overall survival between the WT KRAS and mutated KRAS groups. CONCLUSIONS: In this study, KRAS mutation status did not influence overall survival in either synchronous or metachronous metastatic colorectal adenocarcinoma and, as such, had no prognostic role in this disease setting.
BACKGROUND: Mutations in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in approximately 30% to 40% of colorectal adenocarcinomas. Wild-type (WT) KRAS mutation status is predictive of tumor response with epidermal growth factor receptor-directed therapies, but the results from studies evaluating the prognostic value of KRAS status in localized disease have been contradictory. The prognostic value of KRAS in metastatic disease, specifically according to whether patients have synchronous or metachronous disease at presentation, is less understood. METHODS: One-hundred ten consecutive patients with metastatic colorectal adenocarcinoma underwent testing for KRAS exon 2 mutations by polymerase chain reaction amplification and direct nucleotide sequencing. The clinical characteristics, treatments, and outcomes of these patients were then analyzed retrospectively, stratified according to whether patients presented with synchronous or metachronous metastasis and according to KRAS mutation status (WT or mutated). RESULTS: For the entire cohort, the median overall survival from the date of diagnosis of metastatic disease was 34.3 months (95% confidence interval, 28.3-49.4 months) for patients with WT KRAS (n = 70). The median overall survival for patients with mutated KRAS (n = 40) was 40.3 months (95% confidence interval, 27.9-51.1 months; log-rank P = .91). Kaplan-Meier survival analysis indicated that 3-year overall survival and 5-year overall survival were not statistically different. Within the subgroups of patients with synchronous and metachronous metastatic disease, no significant differences were observed in median overall survival, 3-year overall survival, or 5-year overall survival between the WT KRAS and mutated KRAS groups. CONCLUSIONS: In this study, KRAS mutation status did not influence overall survival in either synchronous or metachronous metastatic colorectal adenocarcinoma and, as such, had no prognostic role in this disease setting.
Authors: Wendy De Roock; Derek J Jonker; Federica Di Nicolantonio; Andrea Sartore-Bianchi; Dongsheng Tu; Salvatore Siena; Simona Lamba; Sabrina Arena; Milo Frattini; Hubert Piessevaux; Eric Van Cutsem; Chris J O'Callaghan; Shirin Khambata-Ford; John R Zalcberg; John Simes; Christos S Karapetis; Alberto Bardelli; Sabine Tejpar Journal: JAMA Date: 2010-10-27 Impact factor: 56.272
Authors: Shuji Ogino; Katsuhiko Nosho; Gregory J Kirkner; Takako Kawasaki; Jeffrey A Meyerhardt; Massimo Loda; Edward L Giovannucci; Charles S Fuchs Journal: Gut Date: 2008-10-02 Impact factor: 23.059
Authors: Timothy J Price; Jennifer E Hardingham; Chee K Lee; Andrew Weickhardt; Amanda R Townsend; Joseph W Wrin; Ann Chua; Aravind Shivasami; Michelle M Cummins; Carmel Murone; Niall C Tebbutt Journal: J Clin Oncol Date: 2011-06-06 Impact factor: 44.544
Authors: Eric Van Cutsem; Claus-Henning Köhne; István Láng; Gunnar Folprecht; Marek P Nowacki; Stefano Cascinu; Igor Shchepotin; Joan Maurel; David Cunningham; Sabine Tejpar; Michael Schlichting; Angela Zubel; Ilhan Celik; Philippe Rougier; Fortunato Ciardiello Journal: J Clin Oncol Date: 2011-04-18 Impact factor: 44.544
Authors: Nicolas Moosmann; Ludwig Fischer von Weikersthal; Ursula Vehling-Kaiser; Martina Stauch; Holger G Hass; Herrmann Dietzfelbinger; Daniel Oruzio; Stefan Klein; Klaus Zellmann; Thomas Decker; Mathias Schulze; Wolfgang Abenhardt; Gerhard Puchtler; Herbert Kappauf; Johann Mittermüller; Christopher Haberl; Andreas Schalhorn; Andreas Jung; Sebastian Stintzing; Volker Heinemann Journal: J Clin Oncol Date: 2011-02-07 Impact factor: 44.544
Authors: Karin Fransén; Maria Klintenäs; Anna Osterström; Jan Dimberg; Hans-Jürg Monstein; Peter Söderkvist Journal: Carcinogenesis Date: 2003-12-19 Impact factor: 4.944
Authors: Arnaud D Roth; Sabine Tejpar; Mauro Delorenzi; Pu Yan; Roberto Fiocca; Dirk Klingbiel; Daniel Dietrich; Bart Biesmans; György Bodoky; Carlo Barone; Enrique Aranda; Bernard Nordlinger; Laura Cisar; Roberto Labianca; David Cunningham; Eric Van Cutsem; Fred Bosman Journal: J Clin Oncol Date: 2009-12-14 Impact factor: 44.544
Authors: Shuji Ogino; Jeffrey A Meyerhardt; Natsumi Irahara; Donna Niedzwiecki; Donna Hollis; Leonard B Saltz; Robert J Mayer; Paul Schaefer; Renaud Whittom; Alexander Hantel; Al B Benson; Richard M Goldberg; Monica M Bertagnolli; Charles S Fuchs Journal: Clin Cancer Res Date: 2009-11-24 Impact factor: 12.531
Authors: Jolien Tol; Miriam Koopman; Annemieke Cats; Cees J Rodenburg; Geert J M Creemers; Jolanda G Schrama; Frans L G Erdkamp; Allert H Vos; Cees J van Groeningen; Harm A M Sinnige; Dirk J Richel; Emile E Voest; Jeroen R Dijkstra; Marianne E Vink-Börger; Ninja F Antonini; Linda Mol; Johan H J M van Krieken; Otilia Dalesio; Cornelis J A Punt Journal: N Engl J Med Date: 2009-02-05 Impact factor: 91.245
Authors: Adriana Rico; Lori A Pollack; Trevor D Thompson; Mei-Chin Hsieh; Xiao-Cheng Wu; Jordan J Karlitz; Dee W West; John M Rainey; Vivien W Chen Journal: J Cancer Res Ther (Manch) Date: 2017-01-30
Authors: Enikő Orosz; István Ember; Katalin Gombos; László Tóth; Ádám Tarpay; Ákos Pap; Szabolcs Ottó Journal: Pathol Oncol Res Date: 2013-07-19 Impact factor: 3.201
Authors: Katharina Ilm; Wolfgang Kemmner; Marc Osterland; Susen Burock; Gudrun Koch; Pia Herrmann; Peter M Schlag; Ulrike Stein Journal: Mol Cancer Date: 2015-02-14 Impact factor: 27.401
Authors: Mariana Petaccia de Macedo; Fernanda Machado de Melo; Júlia da Silva Ribeiro; Celso Abdon Lopes de Mello; Maria Dirlei Ferreira de Souza Begnami; Fernando Augusto Soares; Dirce Maria Carraro; Isabela Werneck da Cunha Journal: Oncoscience Date: 2015-02-09
Authors: Kyu-Pyo Kim; Jeong-Eun Kim; Yong Sang Hong; Sung-Min Ahn; Sung Min Chun; Seung-Mo Hong; Se Jin Jang; Chang Sik Yu; Jin Cheon Kim; Tae Won Kim Journal: Cancer Res Treat Date: 2016-07-04 Impact factor: 4.679