Katsumi Amikura1, Kiwamu Akagi2, Toshiro Ogura3, Amane Takahashi1, Hirohiko Sakamoto1. 1. Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan. 2. Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan. 3. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
INTRODUCTION: We investigated the impact of mutations in KRAS exons 3-4 and NRAS exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients with colorectal liver metastasis (CLM) undergoing hepatic resection. METHODS: We analyzed 421 samples from CLM patients for their all-RAS mutation status to compare the overall survival rate (OS), recurrence-free survival rate (RFS), and the pattern of recurrence between the patients with and without RAS mutations. RESULTS: RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding 79 patients who received anti-EGFR antibody therapy, 168 were classified as all-RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors associated with OS and RFS identified the RAS status as an independent factor (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024). Recurrence with lung metastasis was observed significantly more frequent in patients with RAS mutations than in patients with RAS wild-type (P = 0.0005). CONCLUSIONS: Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy.
INTRODUCTION: We investigated the impact of mutations in KRAS exons 3-4 and NRAS exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients with colorectal liver metastasis (CLM) undergoing hepatic resection. METHODS: We analyzed 421 samples from CLM patients for their all-RAS mutation status to compare the overall survival rate (OS), recurrence-free survival rate (RFS), and the pattern of recurrence between the patients with and without RAS mutations. RESULTS: RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding 79 patients who received anti-EGFR antibody therapy, 168 were classified as all-RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors associated with OS and RFS identified the RAS status as an independent factor (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024). Recurrence with lung metastasis was observed significantly more frequent in patients with RAS mutations than in patients with RAS wild-type (P = 0.0005). CONCLUSIONS: Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy.
Authors: Cristian D Valenzuela; Omeed Moaven; Rohin Gawdi; John A Stauffer; Nico R Del Piccolo; Tan To Cheung; Carlos U Corvera; Andrew D Wisneski; Charles Cha; Christopher W Mangieri; Nima P Zarandi; Justin Dourado; Kathleen C Perry; Gregory Russell; Perry Shen Journal: HPB (Oxford) Date: 2022-02-28 Impact factor: 3.842
Authors: Yoshikuni Kawaguchi; Timothy E Newhook; Hop S Tran Cao; Ching-Wei D Tzeng; Yun Shin Chun; Thomas A Aloia; Arvind Dasari; Scott Kopetz; Jean-Nicolas Vauthey Journal: J Gastrointest Surg Date: 2020-11-17 Impact factor: 3.452