Dataset Information

COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study.

ABSTRACT: Background/Aim:To construct quantitative prognostic models for colorectal cancer (CRC) based on COX-2/C-MET/KRAS expression status in clinical practice. Patients and Methods:Clinical factors and COX-2/C-MET/KRAS expression status of 578 eligible patients from two Chinese hospitals were included. The patients were randomly allocated into training and validation datasets. We created several models using Cox proportional hazard models: SignatureC contained clinical factors, SignatureG contained COX-2/C-MET/KRAS expression status, and SignatureCG contained both. After comparing their accuracy, nomograms for progression-free survival (PFS) and overall survival (OS) were built for the best signatures, with their concordance index and calibration tested. Further, patients were subgrouped by the median of the best signatures, and survival differences between the subgroups were compared. Results:For PFS, among the three signatures, SignaturePFS-CG had the best area under the curve (AUC), with the 1-, 2- and 3-year AUCs being 0.70, 0.73 and 0.89 in the training dataset, respectively and 0.67, 0.73 and 0.87 in the validation dataset, respectively. For OS, the AUCs of SignatureOS-CG for 1-, 2- and 3-years were 0.63, 0.71 and 0.81 in the training dataset, respectively and 0.68, 0.71 and 0.76 in validation dataset, respectively. The nomograms based on SignaturePFS-CG and SignatureOS-CG had good calibrations. Subsequent stratification analysis demonstrated that the subgroups were significantly different for both PFS (training:P < 0.001; validation:P< 0.001) and OS (training:P < 0.001; validation:P < 0.001). Conclusions:Combining clinical factors and COX-2/C-MET/KRAS expression status, our models provided accurate prognostic information in CRC. They can be used to aid treatment decisions in clinical practice.

SUBMITTER: Liu J

PROVIDER: S-EPMC6784436 | biostudies-literature | 2019 Sep-Oct

REPOSITORIES: biostudies-literature

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COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study.

Liu Jianhua J Huang Chengzhi C Wang Junjiang J Huang Ling L Chen Shaojie S

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20190901 5

<h4>Background/aim</h4>To construct quantitative prognostic models for colorectal cancer (CRC) based on COX-2/C-MET/KRAS expression status in clinical practice.<h4>Patients and methods</h4>Clinical factors and COX-2/C-MET/KRAS expression status of 578 eligible patients from two Chinese hospitals were included. The patients were randomly allocated into training and validation datasets. We created several models using Cox proportional hazard models: Signature<sup>C</sup> contained clinical factors ...[more]

PMID: 30720004

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Project description:BackgroundKRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC.Materials and methodsWe retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations.ResultsAmong 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04-1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01-2.00; p = .044).ConclusionWe demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.Implications for practiceAmong patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08-2.01; p = .015) and OS (HR, 1.50; 95% CI, 1.08-2.08; p = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.

Dataset Information

COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study.

Publications

COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study.

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