Effect of KRAS Mutation on Long-Term Outcomes of Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

Margonis, Georgios Antonios; Spolverato, Gaya; Kim, Yuhree; Karagkounis, Georgios; Choti, Michael A.; Pawlik, Timothy M.

doi:10.1245/s10434-015-4587-z

Cited by 89 publications

(52 citation statements)

References 33 publications

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“…7,10 Others noted a correlation between mt-KRAS and only RFS or OS, while yet other reports have failed to find any association between KRAS status and long-term outcomes. 8,9,[11][12][13] Given the findings of the current study, the discrepant results from previous reports might be related to the lack of accounting for primary tumor location. As such, future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site and distinguish between RS and LS tumors.…”

Section: Discussioncontrasting

confidence: 86%

“…[4][5][6] In particular, Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation has been proposed as a potential prognostic factor that may provide both prognostic and therapeutic information for patients undergoing hepatectomy for CRLM. [7][8][9][10] The correlation between Kazunari Sasaki and Georgios A. Margonis have contributed equally to this article, and both should be considered first author.…”

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confidence: 99%

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Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location

et al. 2016

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Section: Discussioncontrasting

confidence: 86%

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confidence: 99%

Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location

et al. 2016

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“…The association of KRAS status on biological pattern of recurrence remains equivocal, however, as other studies have not found an association. Specifically, in a study by Margonis et al, while the prognostic impact of KRAS mutation was validated for OS ( KRAS mutation was associated with worse OS, HR = 1.65; p = 0.02), there was no difference in recurrence pattern among patients undergoing hepatectomy with curative intent for mCRC who had KRAS mutated versus wt KRAS tumors (liver recurrence: 39% v 52.1%, respectively; lung recurrence: 55.6% v 64.3%, respectively; both p > 0.05) [32]. …”

Section: Molecular Markersmentioning

confidence: 99%

Molecular markers of prognosis and therapeutic targets in metastatic colorectal cancer

2016

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Metastatic disease ultimately occurs in approximately 50–70% of patients presenting with colorectal cancer. In patients with advanced disease, there is significant variability in individual patient outcomes. To improve understanding of tumor behavior, markers such as KRAS and BRAF mutation status are increasingly utilized. Additionally, newer surrogates of tumor biology, such as telomerase activity and the prevalence of circulating tumor cells and circulating tumor DNA, have generated increasing interest due to clinical potential. While the extent to which these newer markers can predict outcome and guide therapy is yet to be determined, KRAS mutation status is currently used to guide systemic therapy in selected patients. Furthermore, advances in our understanding of various tumorigenic pathways (such as the mitogen activated protein kinase pathway) have enabled newer targeted agents, including BRAF inhibitors. Interestingly, although inhibition of BRAF in patients has not translated into improved outcomes, characterization of BRAF mutations led to an association with microsatellite instability. A unique histologic characteristic of certain tumors in patients with microsatellite instability is the infiltration by lymphocytes at the tumor-stromal interface. This feature highlights the biology of the tumor in its microenvironment and underlies the efficacy of the programmed-death inhibitor, pembrolizumab, in patients with microsatellite unstable metastatic colorectal cancer. With an increasing number of prognostic markers and therapeutic options in metastatic colorectal cancer, the multidisciplinary approach becomes critical for appropriate treatment decisions.

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“…(10-12) Clinical parameters initially reported as prognostic factors after CLM resection, including CLM size, number of CLM, and carcinoembryonic antigen level, have limited clinical value in the era of modern chemotherapy. (13) Clinicopathological score (3) and pathological response (14, 15) have been reported to be major prognostic factors but can only be evaluated postoperatively following examination of the resected surgical specimen.…”

Section: Introductionmentioning

confidence: 99%

Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases

Passot

Chun

Kopetz

et al. 2016

Journal of the American College of Surgeons

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Background In patients with bilateral colorectal liver metastases (CLM) not resectable in one operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy. Study Design The study included all 109 patients for whom two-stage hepatectomy for CLM was planned during 2003-2014. RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis. Results Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after first stage were disease progression (n=12), insufficient liver growth (n=5), and complications after first stage or portal vein embolization (n=3). More than six cycles of preoperative chemotherapy were associated with failure to proceed to second stage (p=0.009). Rates of major complications (26% vs. 6%; p<0.001) and 90-day mortality (7% vs. 0%; p=0.006) were higher after second stage. The cumulative rate of major complications was 15% (n=29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than one lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs. 6%; p<0.001) and 5-year overall survival rates (49% vs. 0%; p<0.001) were better after two-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p=0.044), more than five CLM (p=0.043), need for chemotherapy after first stage (p=0.046), and RAS mutation (p<0.001). Conclusions RAS mutation independently predicts the oncologic efficacy of two-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy.

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Effect of KRAS Mutation on Long-Term Outcomes of Patients Undergoing Hepatic Resection for Colorectal Liver Metastases

Cited by 89 publications

References 33 publications

Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location

Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location

Molecular markers of prognosis and therapeutic targets in metastatic colorectal cancer

Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases

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