scholarly journals The prognostic value of KRAS mutations in patients with colorectal cancer

2012 ◽  
Vol 28 (5) ◽  
pp. 1579-1584 ◽  
Author(s):  
YASUHIRO INOUE ◽  
SUSUMU SAIGUSA ◽  
TAKASHI IWATA ◽  
YOSHINAGA OKUGAWA ◽  
YUJI TOIYAMA ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Kras Mutations

BRAF and KRAS mutations as additional risk factors in the context of clinical parameters of patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3522-3522
Author(s):  
Vlad Calin Popovici ◽  
Eva Budinska ◽  
Arnaud Roth ◽  
Fred Bosman ◽  
Sabine Tejpar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Tumor Site ◽  
Kras Mutations ◽  
P Values ◽  
Significance Level ◽  
Survival After Relapse

3522 Background: The BRAF and KRAS mutations have been proposed as prognostic markers in colorectal cancer (CRC). Of them, only the BRAF V600E mutation has been validated as prognostic for overall survival and survival after relapse, while the value of KRAS mutation is still unclear. Methods: In a cohort of 1423 stage II-III patients from the PETACC-3 clinical trial, the prognostic value of the BRAF and KRAS mutations was retrospectively assessed in all possible stratifications defined by the 5 factors (T and N stage, tumor site and grade, and microsatellite instability status), by log rank test for overall survival (OS), relapse-free survival (RFS), and survival after relapse (SAR). The presence of interactions was tested by Wald test. The significance level was set to 0.01 for Bonferroni-adjusted p-values (P*), and a second level for a trend towards statistical significance was set at 0.05 for unadjusted p-values (P). Results: BRAF mutation was a marker of poor OS only in microsatellite stable (MSS) and left-sided tumors, with no prognostic value in microsatellite instable (MSI-H) or right-sided tumors. In MSS/left-sided tumors, BRAF mutation represents a marker of higher risk than previously reported: OS HR=6.4 [95% CI: 3.6-11.5], P* < 0.0001. For SAR, BRAF was prognostic in more stratifications, with higher risk in MSS/left-sided tumors (HR=3.9 [95% CI: 2.1-7.2], P* = 0.0002) than in MSS/right-sided (HR=2.3 [95% CI: 1.2-4.4], P=0.01). A novel observation was that BRAF mutation was prognostic also for RFS, but only in MSS/left-sided tumors (HR=3.6 [95% CI:2-6.3], P*=0.0005]). Additionally, heterogeneity in OS and RFS among BRAF mutants was observed. In general, KRAS mutation did not reach the significance level required, but showed a trend to become a prognostic marker for RFS in MSS tumors with early lymph node involvement (N1) (HR=1.6 [95% CI:1.1-2.2], P=0.01). Conclusions: The prognostic utility of the BRAF and KRAS mutations has to be interpreted in the context of other factors. For the BRAF mutation, a clear interaction with MSI status and tumor site was observed, with BRAF mutation indicating a much higher risk in MSS/left-sided tumors than previously considered.

scholarly journals Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

BMC Cancer ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Vlad Popovici ◽  
Eva Budinska ◽  
Fred T Bosman ◽  
Sabine Tejpar ◽  
Arnaud D Roth ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Kras Mutations ◽  
Context Dependent

scholarly journals Prognostic Value of Autophagy, Microsatellite Instability, and KRAS Mutations in Colorectal Cancer

2021 ◽  
Vol 12 (12) ◽  
pp. 3515-3528
Author(s):  
Yuanyuan Wang ◽  
Zhi Zhao ◽  
Jing Zhuang ◽  
Xinxin Wu ◽  
Zhizhong Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Value ◽  
Kras Mutations

Age-dependent prognostic value of KRAS mutation in metastatic colorectal cancer

2021 ◽  
Author(s):  
Muhammet Ozer ◽  
Suleyman Yasin Goksu ◽  
Nina Niu Sanford ◽  
Chul Ahn ◽  
Muhammad Shaalan Beg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Age Groups ◽  
Prognostic Impact ◽  
Kras Gene ◽  
Kras Mutations ◽  
Kras Status ◽  
Age Dependent

Background: The age-dependent prognostic impact of KRAS status in metastatic colorectal cancer (mCRC) is unknown. Materials & Methods: We used the National Cancer Database to evaluate the survival by KRAS status for age-groups <50, 50–69 and ≥70, adjusting for relevant patient and tumor characteristics. Results: mCRC patients (n = 26,095; 33.5%) had KRAS status reported, and 11,338 of these patients (43.4%) had mutations in the KRAS gene. Patients with KRAS mutations had worse overall survival than wild-type KRAS patients. In age-groups <50 years (23 vs 29 months; p < 0.001) and 50–69 (21 vs 23.4 months; p < 0.001), KRAS mutations were significantly associated with worse survival, whereas in the ≥70-year age-group, there was no significant association (14 vs 14 months; p = 0.34). Conclusion: We conclude that the age of patients influences the prognostic value of KRAS mutation in metastatic colorectal cancer.

scholarly journals Prognostic Value of BRAF and KRAS Mutations in Colorectal Cancer Patients

2012 ◽  
Vol 23 ◽  
pp. ix216
Author(s):  
E.P. Murata ◽  
A. Stradella ◽  
D. Páez ◽  
M. Tobeña Puyal ◽  
A. Sebio Garcia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Kras Mutations ◽  
Colorectal Cancer Patients

scholarly journals Study of Ras Mutations’ Prognostic Value in Metastatic Colorectal Cancer: STORIA Analysis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1919
Author(s):  
Alessandro Ottaiano ◽  
Nicola Normanno ◽  
Sergio Facchini ◽  
Antonino Cassata ◽  
Anna Nappi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Survival ◽  
Prognostic Value ◽  
Primary Tumour ◽  
Eastern Cooperative Oncology Group ◽  
Rank Test ◽  
Wild Type ◽  
Kras Mutations ◽  
Thermo Fisher Scientific ◽  
Fisher Scientific

Background: Colorectal cancer (CRC) is the second most common cause of cancer-specific death in both sexes in Western countries. KRAS mutations occur in about 50% of metastatic CRCs (mCRCs). The prognostic value of specific KRAS mutations still remains unexplored and unclear. Methods: Two hundred and forty KRAS wild-type and 206 KRAS/NRAS mutant consecutive unresectable mCRC patients with PS Eastern Cooperative Oncology Group (ECOG) 0 or 1, aged < 80 years, and with a life expectancy >3 months entered into this study. DNA was extracted from paraffin-embedded formalin-fixed tumour tissues, and it was sequenced with the Oncomine Solid Tumour DNA kit (Thermo Fisher Scientific, Waltham, MA, USA). Data were analysed using the Torrent Suite Software v5.0 (Thermo Fisher Scientific). The primary outcome was the analysis of the prognostic role of different KRAS mutations in terms of overall survival (OS). Results: There were no significant differences among the most prevalent mutations (p.G12D, p.G12V, p.G13D, p.G12A, p.G12C, and p.G12S) in terms of age (<65 vs. ≥65 years), gender (male vs. female), grading (G1/G2 vs. G3), side of primary tumour (left vs. right), pT, and pN. At the median follow-up of 25.6 months, there were 77 deaths in KRAS-mutated patients and 94 in wild-type patients. Three homogeneous prognostic groups were identified: wild-type patients (group A, median survival: 27.5 months), p.G13D/p.G12A/p.G12V/p.G12D mutants (group B, median survival: 17.3 months), and p.G12C/p.G12S mutants (group C, median survival: 5.0 months, p < 0.0001 according to Log Rank test). Upon multivariate analysis, metastatic involvement and p.G12C/p.G12S KRAS mutation group C (vs. other mutations) emerged as independent prognostic variables for survival. Conclusions: We show that mutant KRAS is a negative prognostic factor and that p.G12C/p.G12S variants present the worst clinical courses. This information suggests a clear difference among KRAS mutations, and it will be useful to test potentiated and/or innovative therapeutic strategies in p.G12C/p.G12S metastatic CRC patients.

KRASMutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab

2008 ◽  
Vol 26 (3) ◽  
pp. 374-379 ◽  
Author(s):  
Astrid Lièvre ◽  
Jean-Baptiste Bachet ◽  
Valérie Boige ◽  
Anne Cayre ◽  
Delphine Le Corre ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Kras Mutation ◽  
Prognostic Value ◽  
Advanced Colorectal Cancer ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Independent Prognostic Factor ◽  
Allelic Discrimination ◽  
Kras Mutations

PurposeCetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival.Patients and MethodsEighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed.ResultsA KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.ConclusionThese results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.

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