Impact and clinical usefulness of genetic data in the surgical management of colorectal cancer liver metastasis

Importance In patients who undergo surgery for colorectal cancer liver metastases (CRLM), a number of somatic mutations have been associated with worse overall (OS) and recurrence-free survival (RFS). Although useful, an association with prognosis does not necessarily equate to an impact on surgical management. Objective The aim of this review was to investigate whether the best-studied somatic mutations impact surgical management of CRLM by informing: (I) post-hepatectomy surveillance; (II) selection of surgical technique; (III) selection of optimal margin width; and (IV) selection of patients for surgery. Lastly, we discuss the refinement of genetic data from overall mutation status to specific variants, as well as lesser studied somatic mutations. Evidence Review We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to genetic data and CRLM. Findings Genetic data may impact surgical management of CRLM in three ways. Firstly, KRAS mutations can predict lung recurrences. Secondly, KRAS mutations may help tailor margin width. Thirdly, KRAS mutations may help tailor surgical technique. Conclusions Although genetic data may impact post-hepatectomy surveillance, selection of surgical technique and optimal margin width, their use to guide surgical selection remains elusive, as the data cannot support denying surgery to patients according to their somatic mutation profile.

[1]  J. Spicer,et al.  Anatomical Resections Improve Survival Following Lung Metastasectomy of Colorectal Cancer Harboring KRAS Mutations. , 2019, Annals of surgery.

[2]  R. Adam,et al.  Multidisciplinary approach of liver metastases from colorectal cancer , 2019, Annals of gastroenterological surgery.

[3]  I. Endo,et al.  Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis , 2018, Annals of Surgical Oncology.

[4]  Yuhree Kim,et al.  Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases , 2018, The British journal of surgery.

[5]  P. Lønning,et al.  Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer , 2018, JAMA surgery.

[6]  elliot k fishman,et al.  Reply to: "Precision Surgery" for Colorectal Liver Metastases: is the Time Ripe?" , 2019, Annals of surgery.

[7]  J. Vauthey,et al.  SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. , 2018, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[8]  J. Vauthey,et al.  Biomarkers in colorectal liver metastases , 2018, The British journal of surgery.

[9]  Amal Paul,et al.  Devil is in the detail , 2018, BMJ Case Reports.

[10]  J. Cameron,et al.  Microsatellite instability in resectable colorectal liver metastasis: An international multi-institutional analysis. , 2018 .

[11]  J. Vauthey,et al.  Ablation of colorectal liver metastasis: Interaction of ablation margins and RAS mutation profiling on local tumour progression-free survival , 2018, European Radiology.

[12]  P. Lønning,et al.  Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients. , 2018, Annals of surgery.

[13]  K. Haigis KRAS Alleles: The Devil Is in the Detail. , 2017, Trends in cancer.

[14]  M. Choti,et al.  Anatomical Resections Improve Disease-free Survival in Patients With KRAS-mutated Colorectal Liver Metastases , 2017, Annals of surgery.

[15]  J. Vauthey,et al.  Surgery: KRAS mutations and hepatic recurrence after treatment of colorectal liver metastases , 2017, Nature Reviews Gastroenterology & Hepatology.

[16]  O. Lichtarge,et al.  Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in Colorectal Liver Metastases , 2017, Annals of surgery.

[17]  Jonathan H. Chen,et al.  Machine Learning and Prediction in Medicine - Beyond the Peak of Inflated Expectations. , 2017, The New England journal of medicine.

[18]  J. Shindoh,et al.  RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases , 2017, Annals of surgery.

[19]  M. Kendrick,et al.  Impact of Metastasectomy in the Multimodality Approach for BRAF V600E Metastatic Colorectal Cancer: The Mayo Clinic Experience. , 2017, The oncologist.

[20]  Jesse S. Voss,et al.  Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  K. Ahrar,et al.  Local tumour progression after percutaneous ablation of colorectal liver metastases according to RAS mutation status , 2017, The British journal of surgery.

[22]  J. Vauthey,et al.  APC and PIK3CA Mutational Cooperativity Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colorectal Liver Metastases , 2017, Annals of surgery.

[23]  J. Emond,et al.  Recurrence After Liver Transplantation for Hepatocellular Carcinoma: A New MORAL to the Story , 2017, Annals of surgery.

[24]  M. Schaeffer,et al.  KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer , 2016, Oncotarget.

[25]  Yuhree Kim,et al.  Codon 13 KRAS mutation predicts patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases , 2016, Cancer.

[26]  Yuhree Kim,et al.  Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases , 2016, Journal of Gastrointestinal Surgery.

[27]  M. Schaeffer,et al.  Specific KRAS amino acid substitutions and EGFR mutations predict site-specific recurrence and metastasis following non-small-cell lung cancer surgery , 2016, British Journal of Cancer.

[28]  J. Vauthey,et al.  RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases , 2016, Annals of Surgical Oncology.

[29]  A. Russo,et al.  Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis. , 2016, Critical reviews in oncology/hematology.

[30]  M. Chenard,et al.  Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases , 2015, British Journal of Cancer.

[31]  J. Vauthey,et al.  Meta‐analysis of KRAS mutations and survival after resection of colorectal liver metastases , 2015, The British journal of surgery.

[32]  M. Choti,et al.  Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis. , 2015, JAMA surgery.

[33]  G. Fontanini,et al.  BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[34]  M. Choti,et al.  Effect of KRAS Mutation on Long-Term Outcomes of Patients Undergoing Hepatic Resection for Colorectal Liver Metastases , 2015, Annals of Surgical Oncology.

[35]  L. Borsu,et al.  RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer , 2015, Cancer.

[36]  M. D'Angelica,et al.  KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases , 2014, Cancer.

[37]  M. Washington,et al.  PIK3CA and APC mutations are synergistic in the development of intestinal cancers , 2014, Oncogene.

[38]  M. Choti,et al.  Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases , 2013, Cancer.

[39]  Steven A. Curley,et al.  RAS Mutation Status Predicts Survival and Patterns of Recurrence in Patients Undergoing Hepatectomy for Colorectal Liver Metastases , 2013, Annals of surgery.

[40]  John V Heymach,et al.  Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. , 2012, Journal of the National Cancer Institute.

[41]  G. Wahl,et al.  Regulating the p53 pathway: in vitro hypotheses, in vivo veritas , 2006, Nature Reviews Cancer.

[42]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.

[43]  M. Gönen,et al.  Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases?: A Multi-institutional Analysis of 1497 Patients. , 2018, Annals of surgery.

[44]  M. Schaeffer,et al.  Impact of EGFR mutations and KRAS amino acid substitution on the response to radiotherapy for brain metastasis of non-small-cell lung cancer. , 2016, Future oncology.

[45]  Yuhree Kim,et al.  KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases , 2016, Annals of Surgical Oncology.

[46]  M Broggini,et al.  Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.