Abstract

BackgroundIn patients with advanced CRC, KRAS mutations predicts response to treatment with EGFR inhibitor. The Liver metastases selection criteria include anatomic and biological variables. Recent evidence support the prognostic value of KRAS (molecular criteria) in pts with resectable hepatic metastases irrespective of systemic treatment. PURPOSE: To investigate the prognostic value of KRAS in patients undergoing liver resection for colorectal liver metastases (CRLM). Tumour sidedness and tumour burden was also evaluated. MethodsPubmed, Emabase and Cochrane Library databases were searched systematically. Data from published full-text articles reporting KRAS-stratified survival outcomes, recurrence free survival (RFS) and/or overall survival (OS) after resection of CRLM cancer. METHEPAR results, a local multi-institutional CRLM database, was also included. Hazard ratios (HR) and 95% CI from analyses were pooled in meta-analysis, and a random-effects model was used to calculate overall results. ResultsThe search returned 69 articles, of which 20, including METHEPAR, met the inclusion criteria. A total of 3819 patients were included. The mutation rate was 33.5% (IQR: 26.3-38.5). Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.55; 95% CI: 1.38-1.75) and OS (HR: 1.85; 95% CI: 1.57-2.19) in patients who underwent surgical resection of CRLM. In a subgroup analysis regarding sideness, studies involving more proportion of ptes with right sided tumours, had similar OS compare to those with proportion (HR:1.74; 95% CI 1.40; 2.16) p=0.19. Liver-only mets had a similar OS compare to those with more disseminated diseasés burden (HR:1.76;95% CI1.46; 2.12). ConclusionsThis meta-analysis confirm, as in previous one that KRAS mutations is a poor prognostic biomarker, associated with worse survival outcomes, in patients undergoing hepatic resection of CRLM, regardless of tumor sidedness and disease burden. KRAS mutation should be considered in the evaluation of pts. having liver metastasis for surgical resection. Legal entity responsible for the studyAlexander Fleming Institute. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

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