Lily V Saadat1, Thomas Boerner2, Debra A Goldman3, Mithat Gonen3, Timothy L Frankel4, Efsevia Vakiani5, T Peter Kingham2, William R Jarnagin2, Alice C Wei2, Kevin C Soares2, David B Solit6,7, Michael I D'Angelica2. 1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. saadatl@mskcc.org. 2. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Surgery, University of Michigan, Ann Arbor, MI, USA. 5. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7. Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract
BACKGROUND: RAS mutations are prognostic for patients with metastatic colorectal cancer (mCRC). We investigated clinical, pathologic, and survival differences based on RAS exon for patients with colorectal liver metastases (CRLM). METHODS: This retrospective, single-center study included patients with R0/R1 resection of CRLM from 1992 to 2016. Patients with unresected extrahepatic disease or liver-first resection were excluded. Overall survival (OS) and recurrence-free survival were assessed and stratified by mutation status and location. Fisher's exact test, Wilcoxon rank-sum test, and log-rank test were used, where appropriate. RESULTS: A total of 938 mCRC patients were identified with median age of 57 (range 19-91). Of the 445 patients with KRAS mutations, 407 (91%) had a mutation in exon 2, 14 (3%) exon 3, and 24 (5%) exon 4. Median OS was 71.4 months (95% confidence interval [CI] 66.1-76.5). Patients with KRAS mutations had worse OS compared with KRAS wild-type patients (median 55.5 vs. 91.3 months, p < 0.001). While there was no significant difference in OS based on the exon mutated (p = 0.12), 5-year OS was higher for patients with exon 4 mutations [68.8% (95% CI 0.45-0.84)] compared with those with mutations in exon 2 [45.7% (95% CI 0.40-0.51)] or exon 3 [39.1% (95% CI: 0.11-0.68)]. Patients with NRAS mutant tumors also had worse OS compared with NRAS wild-type patients (median 50.9 vs. 73.3 months, p = 0.03). CONCLUSIONS: NRAS and KRAS exon 3/4 mutations are present in a minority of mCRC patients. Patients with exon 4 mutant tumors may have a more favorable prognosis, although the difference in oncologic outcomes based on mutated exon appears to be smaller than previously reported.
BACKGROUND: RAS mutations are prognostic for patients with metastatic colorectal cancer (mCRC). We investigated clinical, pathologic, and survival differences based on RAS exon for patients with colorectal liver metastases (CRLM). METHODS: This retrospective, single-center study included patients with R0/R1 resection of CRLM from 1992 to 2016. Patients with unresected extrahepatic disease or liver-first resection were excluded. Overall survival (OS) and recurrence-free survival were assessed and stratified by mutation status and location. Fisher's exact test, Wilcoxon rank-sum test, and log-rank test were used, where appropriate. RESULTS: A total of 938 mCRC patients were identified with median age of 57 (range 19-91). Of the 445 patients with KRAS mutations, 407 (91%) had a mutation in exon 2, 14 (3%) exon 3, and 24 (5%) exon 4. Median OS was 71.4 months (95% confidence interval [CI] 66.1-76.5). Patients with KRAS mutations had worse OS compared with KRAS wild-type patients (median 55.5 vs. 91.3 months, p < 0.001). While there was no significant difference in OS based on the exon mutated (p = 0.12), 5-year OS was higher for patients with exon 4 mutations [68.8% (95% CI 0.45-0.84)] compared with those with mutations in exon 2 [45.7% (95% CI 0.40-0.51)] or exon 3 [39.1% (95% CI: 0.11-0.68)]. Patients with NRAS mutant tumors also had worse OS compared with NRAS wild-type patients (median 50.9 vs. 73.3 months, p = 0.03). CONCLUSIONS: NRAS and KRAS exon 3/4 mutations are present in a minority of mCRC patients. Patients with exon 4 mutant tumors may have a more favorable prognosis, although the difference in oncologic outcomes based on mutated exon appears to be smaller than previously reported.
Authors: Efsevia Vakiani; Manickam Janakiraman; Ronglai Shen; Rileen Sinha; Zhaoshi Zeng; Jinru Shia; Andrea Cercek; Nancy Kemeny; Michael D'Angelica; Agnes Viale; Adriana Heguy; Philip Paty; Timothy A Chan; Leonard B Saltz; Martin Weiser; David B Solit Journal: J Clin Oncol Date: 2012-06-04 Impact factor: 44.544
Authors: Andrea Cercek; Maria Ignez Braghiroli; Joanne F Chou; Jaclyn F Hechtman; Nancy Kemeny; Leonard Saltz; Marinela Capanu; Rona Yaeger Journal: Clin Cancer Res Date: 2017-04-26 Impact factor: 12.531
Authors: Timothy L Frankel; Efsevia Vakiani; Hari Nathan; Ronald P DeMatteo; T Peter Kingham; Peter J Allen; William R Jarnagin; Nancy E Kemeny; David B Solit; Michael I D'Angelica Journal: Cancer Date: 2016-10-13 Impact factor: 6.860
Authors: Yufang Wang; Sérgia Velho; Efsevia Vakiani; Shouyong Peng; Adam J Bass; Gerald C Chu; Jessica Gierut; James M Bugni; Channing J Der; Mark Philips; David B Solit; Kevin M Haigis Journal: Cancer Discov Date: 2012-12-28 Impact factor: 39.397
Authors: Claire B Pollock; Senji Shirasawa; Takehiko Sasazuki; Walter Kolch; Amardeep S Dhillon Journal: Cancer Res Date: 2005-02-15 Impact factor: 12.701
Authors: Jashodeep Datta; J Joshua Smith; Walid K Chatila; John C McAuliffe; Cyriac Kandoth; Efsevia Vakiani; Timothy L Frankel; Karuna Ganesh; Isaac Wasserman; Marla Lipsyc-Sharf; Jose Guillem; Garrett M Nash; Philip B Paty; Martin R Weiser; Leonard B Saltz; Michael F Berger; William R Jarnagin; Vinod Balachandran; T Peter Kingham; Nancy E Kemeny; Andrea Cercek; Julio Garcia-Aguilar; Barry S Taylor; Agnes Viale; Rona Yaeger; David B Solit; Nikolaus Schultz; Michael I D'Angelica Journal: Clin Cancer Res Date: 2019-11-12 Impact factor: 12.531
Authors: Timothy S Maughan; Richard A Adams; Christopher G Smith; Angela M Meade; Matthew T Seymour; Richard H Wilson; Shelley Idziaszczyk; Rebecca Harris; David Fisher; Sarah L Kenny; Edward Kay; Jenna K Mitchell; Ayman Madi; Bharat Jasani; Michelle D James; John Bridgewater; M John Kennedy; Bart Claes; Diether Lambrechts; Richard Kaplan; Jeremy P Cheadle Journal: Lancet Date: 2011-06-05 Impact factor: 79.321
Authors: Ahmet Zehir; Ryma Benayed; Ronak H Shah; Aijazuddin Syed; Sumit Middha; Hyunjae R Kim; Preethi Srinivasan; Jianjiong Gao; Debyani Chakravarty; Sean M Devlin; Matthew D Hellmann; David A Barron; Alison M Schram; Meera Hameed; Snjezana Dogan; Dara S Ross; Jaclyn F Hechtman; Deborah F DeLair; JinJuan Yao; Diana L Mandelker; Donavan T Cheng; Raghu Chandramohan; Abhinita S Mohanty; Ryan N Ptashkin; Gowtham Jayakumaran; Meera Prasad; Mustafa H Syed; Anoop Balakrishnan Rema; Zhen Y Liu; Khedoudja Nafa; Laetitia Borsu; Justyna Sadowska; Jacklyn Casanova; Ruben Bacares; Iwona J Kiecka; Anna Razumova; Julie B Son; Lisa Stewart; Tessara Baldi; Kerry A Mullaney; Hikmat Al-Ahmadie; Efsevia Vakiani; Adam A Abeshouse; Alexander V Penson; Philip Jonsson; Niedzica Camacho; Matthew T Chang; Helen H Won; Benjamin E Gross; Ritika Kundra; Zachary J Heins; Hsiao-Wei Chen; Sarah Phillips; Hongxin Zhang; Jiaojiao Wang; Angelica Ochoa; Jonathan Wills; Michael Eubank; Stacy B Thomas; Stuart M Gardos; Dalicia N Reales; Jesse Galle; Robert Durany; Roy Cambria; Wassim Abida; Andrea Cercek; Darren R Feldman; Mrinal M Gounder; A Ari Hakimi; James J Harding; Gopa Iyer; Yelena Y Janjigian; Emmet J Jordan; Ciara M Kelly; Maeve A Lowery; Luc G T Morris; Antonio M Omuro; Nitya Raj; Pedram Razavi; Alexander N Shoushtari; Neerav Shukla; Tara E Soumerai; Anna M Varghese; Rona Yaeger; Jonathan Coleman; Bernard Bochner; Gregory J Riely; Leonard B Saltz; Howard I Scher; Paul J Sabbatini; Mark E Robson; David S Klimstra; Barry S Taylor; Jose Baselga; Nikolaus Schultz; David M Hyman; Maria E Arcila; David B Solit; Marc Ladanyi; Michael F Berger Journal: Nat Med Date: 2017-05-08 Impact factor: 53.440
Authors: Pim B Olthof; Stefan Buettner; Nikolaos Andreatos; Jane Wang; Inger Marie Løes; Doris Wagner; Kazunari Sasaki; Andrea Macher-Beer; Carsten Kamphues; Ioannis Pozios; Hendrik Seeliger; Daisuke Morioka; Katsunori Imai; Klaus Kaczirek; Timothy M Pawlik; George Poultsides; Richard Burkhart; Itaru Endo; Hideo Baba; Peter Kornprat; Federico N Aucejo; Per Eystein Lønning; Katharina Beyer; Matthew J Weiss; Christopher L Wolfgang; Martin E Kreis; Georgios A Margonis Journal: Br J Surg Date: 2022-08-16 Impact factor: 11.122