scholarly journals A Nomogram for the Prediction of Kras Mutation in Colorectal Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 34s-34s
Author(s):  
W. Xiang ◽  
G. Cai
Keyword(s):  
Colorectal Cancer ◽  
Logistic Regression ◽  
Kras Mutation ◽  
Predictive Accuracy ◽  
Multivariate Logistic Regression Model ◽  
Cancer Center ◽  
Multivariate Logistic Regression ◽  
Kras Mutations ◽  
Mutation Status ◽  
Kras Mutation Status

Background: KRAS mutation status is crucial in treatment decisions regarding the use of EGFR tyrosine kinase inhibitors in colorectal cancer (CRC). However, genetic testing is not available for some patients, either because tissue is limited and/or tests are not routinely offered. Aim: We aimed to build a nomogram based on clinical factors for the prediction of KRAS mutations in CRC. Methods: Colorectal cancer patients who had their tumors genotyped for KRAS mutation at Fudan University Shanghai Cancer Center (FUSCC) were retrospectively analyzed. Variables of interest were integrated in a multivariate logistic regression model. Results: A total of 759 hospitalized patients were extracted from FUSCC database. KRAS mutation presented in 40.1% (309/759) cases. Multivariate logistic regression suggested that female (OR 1.47, 95% CI 1.06-2.04), mucinous histology (OR 2.04, 95% CI 1.28-3.25), right-sided tumor (OR 1.65, 95% CI 1.13-2.39) and high levels of preoperative CEA (OR 1.45, 95% CI 1.03-2.03), CA19-9 (OR 3.87, 95% CI 2.70-5.53) and albumin/globular protein (OR 2.02, 95% CI 1.33-3.06) were significantly correlated with KRAS mutation status. A nomogram was established and showed considerable discriminating accuracy (AUC 0.744, 95% CI 0.709-0.779) in this cohort. Patients with the highest score had 88.6% chance to bear a KRAS-mutant tumor. Subgroup analysis based on metastasis status revealed a sound applicability of the established nomogram both in metastatic (AUC 0.723, 95% CI 0.666-0.781) and nonmetastatic (AUC 0.753, 95% CI 0.707-0.798) CRC. Conclusion: Six simple and easy-to-collect characteristics defined a useful nomogram to predict KRAS status both in metastatic and nonmetastatic CRC with great predictive accuracy.

scholarly journals The value of haematological parameters and serum tumour markers for predicting KRAS mutations in 784 Chinese colorectal cancer patients: a retrospective analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yinghao Cao ◽  
Junnan Gu ◽  
Lizhao Yan ◽  
Shenghe Deng ◽  
Fuwei Mao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Logistic Regression ◽  
Predictive Value ◽  
Gene Mutations ◽  
Haematological Parameters ◽  
Multivariate Logistic Regression ◽  
Kras Gene ◽  
Kras Mutations ◽  
Mutation Status ◽  
Serum Tumour

Abstract Background Identifying the mutation status of KRAS is important for optimizing treatment in patients with colorectal cancer (CRC). The aim of this study was to investigate the predictive value of haematological parameters and serum tumour markers (STMs) for KRAS gene mutations. Methods The clinical data of patients with colorectal cancer from January 2014 to December 2018 were retrospectively collected, and the associations between KRAS mutations and other indicators were analysed. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. Univariate and multivariate logistic regression models were applied to identify predictors of KRAS mutations by calculating the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Results KRAS mutations were identified in 276 patients (35.2%). ROC analysis revealed that age, CA12–5, AFP, SCC, CA72–4, CA15–3, FERR, CYFRA21-1, MCHC, and tumor location could not predict KRAS mutations (P = 0.154, 0.177, 0.277, 0.350, 0.864, 0.941, 0.066, 0.279, 0.293, and 0.053 respectively), although CEA, CA19–9, NSE and haematological parameter values showed significant predictive value (P = 0.001, < 0.001, 0.043 and P = 0.003, < 0.001, 0.001, 0.031, 0.030, 0.016, 0.015, 0.019, and 0.006, respectively) but without large areas under the curve. Multivariate logistic regression analysis showed that CA19–9 was significantly associated with KRAS mutations and was the only independent predictor of KRAS positivity (P = 0.016). Conclusions Haematological parameters and STMs were related to KRAS mutation status, and CA19–9 was an independent predictive factor for KRAS gene mutations. The combination of these clinical factors can improve the ability to identify KRAS mutations in CRC patients.

KRAS mutation as a prognostic factor in patients undergoing hepatic resection for metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 444-444
Author(s):  
Justin John Baker ◽  
Rachel Aufforth ◽  
James Todd Auman ◽  
Robert Eil ◽  
Howard L. McLeod ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Tumor Biology ◽  
Disease Free Survival ◽  
Kras Mutations ◽  
Mutation Status ◽  
Cetuximab Therapy ◽  
Kras Mutation Status

444 Background: It is well known that KRAS mutations limit the efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer (mCRC). However the role of KRAS mutations in patients who undergo a curative liver resection for mCRC is less clear. The purpose of our study was to evaluate the relationship between KRAS mutation status and survival in this patient population. Methods: We examined an IRB approved tissue repository and retrospective database of 129 patients from 1998-2010 who underwent curative liver resection for mCRC. Tumors were sequenced for KRAS codons 12, 13, and 61 mutations using pyrosequencing. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression method. Results: The median follow-up for our cohort was 20.4mo (0.4-112). Mean age was 61.4±12.3. Prior to surgical resection 55 (43%) patients received chemotherapy. 35 (27%) tumors were KRAS mutant (mt), 83 (64%) were wild-type (wt), and 11 (9%) were not characterized. Median OS for KRAS wt patients was 40.3mo vs. 27.1mo for KRAS mt patients (p=0.046). Median DFS for KRAS wt was 13.6mo vs. 7.7mo for KRAS mt patients (p=0.037). 8 patients received cetuximab post–operatively. Cetuximab status was unknown in 50 patients. When we excluded those treated with cetuximab, the median OS was 40mo for KRAS wt vs. 25mo for KRAS mt patients (p=0.007). There were no differences in OS or DFS in patients who received cetuximab (p=0.7). In a multivariable model with pre-operative chemotherapy (p=0.2), extent of resection (p=0.053), and cetuximab therapy (p=0.7), the presence of KRAS mutation was independently associated with poor prognosis (HR=2.7 [1.3-5.5]). Conclusions: In patients undergoing curative liver resection for mCRC, KRAS mutation status is independently predictive of a worse outcome regardless of cetuximab therapy. KRAS status may be associated with more aggressive tumor biology. Our data supports the critical need to define KRAS mutation status and to develop therapies against KRAS and its downstream effectors.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

scholarly journals Ανίχνευση μεταλλάξεων του EGFR και KRAS σε ασθενείς με μη-μικροκυτταρικό καρκίνο του πνεύμονα και διερεύνηση της αξίας τους ως προβλεπτικών παραγόντων ανταπόκρισης στη θεραπεία

2013 ◽  
Author(s):  
Αριστέα Καλυκάκη
Keyword(s):  
Kras Mutation ◽  
Smoking History ◽  
Egfr Mutations ◽  
Front Line ◽  
Kras Mutations ◽  
Primary Tumors ◽  
Mutation Status ◽  
Kras Mutation Status ◽  
Line Chemotherapy ◽  
Exon 19

The purpose of this study was to investigate whether the EGFR and KRASmutation status are predictive factors for Greeks patients with NSCLC. Initially, wecalculated the rate and the pattern of EGFR and KRAS mutations in 639 patients withNSCLC and then we correlated the mutations status with clinicopathologicalcharacteristics, the response to 1st line chemotherapy and patients’ overall survival.We also investigated the association of EGFR mutations with the EGFR geneamplification. Finally, in a group of 25 patients the mutation status of these genes inthe primary tumors and the corresponding metastasis was evaluated.The genetic analysis performed in FFPE tissue samples of primary tumor ormetastasis. DNA was extracted using universal techniques. For mutation analysis exons18, 19, 20 and 21 of the EGFR and exon 2 of KRAS genes were sequentially amplified bypolymerase chain reaction (PCR) and subjected to direct sequencing. Finally, EGFRamplification was determined by quantitative real time PCR.Analysis of EGFR mutations was successful performed in 634 patients andmutations were detected in 100 (15.8%) of them. Activating mutations were detected in 8.4%. The most common mutations were deletions of 4-5 codons in exon 19 (del 19,71.7%, 38/53) and the missense mutation at position 858 (L858R) in exon 21 (22.6%,12/53). Also in 47 (7.4%) patients other mutations were detected in four exons ofEGFR, which have been reported previously or are new. We found that the incidenceof EGFR mutations was statistically significant in women with no smoking history andwith adenocarcinoma histology.The mutation analysis of the KRAS gene was successfully performed on 399patients and mutations detected in 20.8% of them (83/399). Especially, 92.8% of themutations were found at codon 12 and 7.2% at codon 13. KRAS mutations weresignificantly associated with smoking history with higher incidence in smokers thannonsmokers. There was also a significant association between KRAS mutations andadenocarcinoma histology.The predictive value of EGFR and KRAS mutations was examined in a subgroupof patients (n=162) with NSCLC who received chemotherapy as 1st line therapy.Patients with classical EGFR mutations had a higher probability of response (55.6%) to front-line chemotherapy as compared to those with wild type EGFR (21.8%) (p =0.023). Multivariate analysis revealed the 'classical' activating EGFR mutations as anindependent predictive factor for response to 1st line chemotherapy. There was nosignificant correlation between the EGFR or KRAS mutation status and the time totumor progression. The presence of activating EGFR but not of KRAS mutations wasassociated with a significantly higher overall survival compared to patients withoutmutations treated with platinum-based front-line chemotherapy.Epidermal growth factor receptor and KRAS mutation status was differentbetween primary tumors and corresponding metastases in 7 (28%) and 6 (24%) of the25 patients, respectively. This discrepancy was not statistically significant with theMcNemar’s test.EGFR amplification was found in 7.2% (6/83) of primary tumors. Among thepatients with EGFR gene amplification none carried KRAS mutations while 2 had EGFR exon 19 deletion.

scholarly journals Cigarette Smoking and Colorectal Cancer Risk by KRAS Mutation Status Among Older Women

2012 ◽  
Vol 107 (5) ◽  
pp. 782-789 ◽  
Author(s):  
N J Samadder ◽  
Robert A Vierkant ◽  
Lori S Tillmans ◽  
Alice H Wang ◽  
Charles F Lynch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Cigarette Smoking ◽  
Older Women ◽  
Kras Mutation ◽  
Colorectal Cancer Risk ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals KRAS mutation status, comorbidity, and mortality in patients with metastatic colorectal cancer in Denmark

2018 ◽  
Vol 57 (12) ◽  
pp. 1727-1729
Author(s):  
Anne Gulbech Ording ◽  
Buket Öztürk ◽  
Karen-Lise Garm Spindler ◽  
Henrik Toft Sørensen ◽  
Margaret McCusker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals SUVmax and metabolic tumor volume: surrogate image biomarkers of KRAS mutation status in colorectal cancer

2019 ◽  
Vol Volume 12 ◽  
pp. 2115-2121 ◽  
Author(s):  
Ying Lv ◽  
Xin Wang ◽  
Lerong Liang ◽  
Lei Wang ◽  
Jie Lu
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals Relationships between KRAS mutation status and baseline radiographic distribution of disease in patients with stage IV colorectal cancer

2014 ◽  
Vol 39 (6) ◽  
pp. 1261-1266 ◽  
Author(s):  
Michael H. Rosenthal ◽  
Kyung Won Kim ◽  
Charles S. Fuchs ◽  
Jeffrey A. Meyerhardt ◽  
Nikhil H. Ramaiya
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Stage Iv ◽  
Mutation Status ◽  
Stage Iv Colorectal Cancer ◽  
Kras Mutation Status
Sign in / Sign up

Export Citation Format

Share Document