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Anatomical Resections Improve Disease Free Survival in Patients with KRAS-Mutated Colorectal Liver Metastases
Georgios Antonios Margonis1, Stefan Buettner1, Kazunari Sasaki1, Nikolaos Andreatos1, Jan N.M. IJzermans2, Jeroen L.A. van Vugt2, John L. Cameron1, Jin He*1, Christopher L. Wolfgang1, Matthew Weiss*1
1Johns Hopkins Hospital, Baltimore, MD;2Erasmus MC, Rotterdam, Netherlands

Objective: KRAS-mutated colorectal liver metastases(CRLM) are known to be more aggressive than KRAS wild-type tumors. Although non-anatomical 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 Cox Proportional Hazards.
Results: 165 patients(42.6%) underwent anatomical resections and 141(36.2%) presented with KRAS-mutated CRLM. Median disease free survival(DFS) in the entire cohort was 21.3 months, while 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 non-anatomical resections in patients with KRAS wild-type tumors(p=0.116), 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)(Figure). Five-year DFS was only 15.5% in the non-anatomically resected group, versus 46.4% in the anatomically resected group. This observation persisted in multivariable analysis(HR:0.53; 95%CI: 0.32-0.88;p=0.015), when corrected for disease-free interval, lymph-node status, tumor size and number, perioperative chemotherapy, and margin status.
Conclusion: Non-anatomical tissue-sparing hepatectomies are associated with worse DFS in patients with KRAS-mutated tumors. Due to the aggressive nature of KRAS-mutated CRLM, more extensive anatomical hepatectomies may be warranted.

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