Dataset Information

Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases.

ABSTRACT: PURPOSE:Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection. EXPERIMENTAL DESIGN:We identified patients who underwent initial CLM resection during 2007-2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models. RESULTS:Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P = 0.858 and 0.729, respectively). CONCLUSIONS:RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.

SUBMITTER: Kawaguchi Y

PROVIDER: S-EPMC6774854 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Mutation Status of <i>RAS, TP53</i>, and <i>SMAD4</i> is Superior to Mutation Status of <i>RAS</i> Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases.

Kawaguchi Yoshikuni Y Kopetz Scott S Newhook Timothy E TE De Bellis Mario M Chun Yun Shin YS Tzeng Ching-Wei D CD Aloia Thomas A TA Vauthey Jean-Nicolas JN

Clinical cancer research : an official journal of the American Association for Cancer Research 20190620 19

<h4>Purpose</h4>Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection.<h4>Experimental design</h4>We identified patients who underwent initial CLM resection during 2007-2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were dete ...[more]

PMID: 31221662

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Project description:BackgroundMost current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables.MethodsA prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort.ResultsA total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases.ConclusionThe contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.

Dataset Information

Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases.

Publications

Mutation Status of <i>RAS, TP53</i>, and <i>SMAD4</i> is Superior to Mutation Status of <i>RAS</i> Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases.

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