Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases

Georgios A. Margonis, Stefan Buettner, Nikolaos Andreatos, Kazunari Sasaki, Jan N.M. Ijzermans, Jeroen L.A. van Vugt, Timothy M. Pawlik, Michael A. Choti, John L. Cameron, Jin He, Christopher L. Wolfgang, Matthew J. Weiss

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE:: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. BACKGROUND:: KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. METHODS:: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS:: In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27–0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. CONCLUSIONS:: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

Original languageEnglish (US)
JournalAnnals of Surgery
DOIs
StateAccepted/In press - Jun 27 2017

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Disease-Free Survival
Neoplasm Metastasis
Liver
Hepatectomy
Neoplasms
Proportional Hazards Models
Confidence Intervals
Mutation
Survival

ASJC Scopus subject areas

  • Surgery

Cite this

Margonis, G. A., Buettner, S., Andreatos, N., Sasaki, K., Ijzermans, J. N. M., van Vugt, J. L. A., ... Weiss, M. J. (Accepted/In press). Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases. Annals of Surgery. https://doi.org/10.1097/SLA.0000000000002367

Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases. / Margonis, Georgios A.; Buettner, Stefan; Andreatos, Nikolaos; Sasaki, Kazunari; Ijzermans, Jan N.M.; van Vugt, Jeroen L.A.; Pawlik, Timothy M.; Choti, Michael A.; Cameron, John L.; He, Jin; Wolfgang, Christopher L.; Weiss, Matthew J.

In: Annals of Surgery, 27.06.2017.

Research output: Contribution to journalArticle

Margonis, GA, Buettner, S, Andreatos, N, Sasaki, K, Ijzermans, JNM, van Vugt, JLA, Pawlik, TM, Choti, MA, Cameron, JL, He, J, Wolfgang, CL & Weiss, MJ 2017, 'Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases', Annals of Surgery. https://doi.org/10.1097/SLA.0000000000002367
Margonis, Georgios A. ; Buettner, Stefan ; Andreatos, Nikolaos ; Sasaki, Kazunari ; Ijzermans, Jan N.M. ; van Vugt, Jeroen L.A. ; Pawlik, Timothy M. ; Choti, Michael A. ; Cameron, John L. ; He, Jin ; Wolfgang, Christopher L. ; Weiss, Matthew J. / Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases. In: Annals of Surgery. 2017.
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title = "Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases",
abstract = "OBJECTIVE:: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. BACKGROUND:: KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. METHODS:: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS:: In this study, 165 patients (42.4{\%}) underwent nonanatomical resections and 140 (36.0{\%}) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3{\%}, 34.9{\%}, and 31.5{\%} respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4{\%} in the nonanatomically resected group, versus 46.4{\%} in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95{\%} confidence interval: 0.27–0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. CONCLUSIONS:: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.",
author = "Margonis, {Georgios A.} and Stefan Buettner and Nikolaos Andreatos and Kazunari Sasaki and Ijzermans, {Jan N.M.} and {van Vugt}, {Jeroen L.A.} and Pawlik, {Timothy M.} and Choti, {Michael A.} and Cameron, {John L.} and Jin He and Wolfgang, {Christopher L.} and Weiss, {Matthew J.}",
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T1 - Anatomical Resections Improve Disease-Free Survival in Patients With KRAS-mutated Colorectal Liver Metastases

AU - Margonis, Georgios A.

AU - Buettner, Stefan

AU - Andreatos, Nikolaos

AU - Sasaki, Kazunari

AU - Ijzermans, Jan N.M.

AU - van Vugt, Jeroen L.A.

AU - Pawlik, Timothy M.

AU - Choti, Michael A.

AU - Cameron, John L.

AU - He, Jin

AU - Wolfgang, Christopher L.

AU - Weiss, Matthew J.

PY - 2017/6/27

Y1 - 2017/6/27

N2 - OBJECTIVE:: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. BACKGROUND:: KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. METHODS:: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS:: In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27–0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. CONCLUSIONS:: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

AB - OBJECTIVE:: To investigate the potential clinical advantage of anatomical resection versus nonanatomical resection for colorectal liver metastases, according to KRAS mutational status. BACKGROUND:: KRAS-mutated colorectal liver metastases (CRLM) are known to be more aggressive than KRAS wild-type tumors. Although nonanatomical liver resections have been demonstrated as a viable approach for CRLM patients with similar oncologic outcomes to anatomical resections, this may not be the case for the subset of KRAS-mutated CRLM. METHODS:: 389 patients who underwent hepatic resection of CRLM with known KRAS mutational status were identified. Survival estimates were calculated using the Kaplan-Meier method, and multivariable analysis was conducted using the Cox proportional hazards regression model. RESULTS:: In this study, 165 patients (42.4%) underwent nonanatomical resections and 140 (36.0%) presented with KRAS-mutated CRLM. Median disease-free survival (DFS) in the entire cohort was 21.3 months, whereas 1-, 3-, and 5-year DFS was 67.3%, 34.9%, and 31.5% respectively. Although there was no difference in DFS between anatomical and nonanatomical resections in patients with KRAS wild-type tumors (P = 0.142), a significant difference in favor of anatomical resection was observed in patients with a KRAS mutation (10.5 vs. 33.8 months; P < 0.001). Five-year DFS was only 14.4% in the nonanatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis (hazard ratio: 0.45; 95% confidence interval: 0.27–0.74; P = 0.002), when corrected for number of tumors, bilobar disease, and intraoperative ablations. CONCLUSIONS:: Nonanatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Because of the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

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