TY - JOUR
T1 - RAS/TP53 Co-mutation is Associated with Worse Survival after Concurrent Resection of Colorectal Liver Metastases and Extrahepatic Disease
AU - Lillemoe, Heather A.
AU - Passot, Guillaume
AU - Kawaguchi, Yoshikuni
AU - Debellis, Mario
AU - Glehen, Olivier
AU - Chun, Yun Shin
AU - Tzeng, Ching Wei D.
AU - Aloia, Thomas A
AU - Lopez, Jonathan
AU - Vauthey, Jean Nicolas
N1 - Funding Information:
Dr. Heather Lillemoe was supported by the National Institutes of Health grant T32CA009599 and the MD Anderson Cancer Center support grant (P30CA016672).
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Objective: To determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD). Summary Background Data: The prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported. Methods: Patients undergoing concurrent resection of CLM and EHD from 2007 to 2017 were identified from 2 academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytore-ductive surgery with hyperthermic intraperitoneal chemotherapy. The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed. Results: One hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (interquartile range, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/ TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months (P = 0.02). On multivariable analysis, lung EHD [hazard ratio (HR), 0.7; 95% confidence intervals (CI), 0.3-1.4], peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS. Conclusions: RAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.
AB - Objective: To determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD). Summary Background Data: The prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported. Methods: Patients undergoing concurrent resection of CLM and EHD from 2007 to 2017 were identified from 2 academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytore-ductive surgery with hyperthermic intraperitoneal chemotherapy. The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed. Results: One hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (interquartile range, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/ TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months (P = 0.02). On multivariable analysis, lung EHD [hazard ratio (HR), 0.7; 95% confidence intervals (CI), 0.3-1.4], peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS. Conclusions: RAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.
KW - cancer surgery
KW - colorectal liver metastases
KW - extrahepatic disease
KW - genetic sequencing
UR - http://www.scopus.com/inward/record.url?scp=85134383764&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134383764&partnerID=8YFLogxK
U2 - 10.1097/SLA.0000000000004672
DO - 10.1097/SLA.0000000000004672
M3 - Article
C2 - 33351476
AN - SCOPUS:85134383764
SN - 0003-4932
VL - 276
SP - 357
EP - 362
JO - Annals of surgery
JF - Annals of surgery
IS - 2
ER -