Association of KRAS mutation with worse recurrence-free survival and site of metastatic progression after resection of hepatic colorectal metastases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3609-3609 ◽  
Author(s):  
Nancy E. Kemeny ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Alexandra N. Gewirtz ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Liver Metastases ◽  
Cumulative Incidence ◽  
Kras Mutation ◽  
Colorectal Metastases ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Number Of Patients ◽  
Kras Mutation Status

3609 Background: There are conflicting results regarding the influence of KRAS mutation status and outcome in patients (pts) with colorectal cancer. A recent report suggested worse outcome in KRAS mutated (MUT) pts who underwent resection of hepatic metastases (Karagkounis et al, ASCO 2012). Methods: Recurrence patterns and survival were evaluated in 169 patients who had undergone resection of liver metastases, then received adjuvant hepatic arterial infusion and systemic chemotherapy, and for whom KRAS data were available. Kaplan-Meier methods were used to estimate recurrence free survival (RFS) and overall survival (OS). Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adjuvant therapy to bone, brain, lung and liver metastases separately. Mutations in KRAS (codons 12, 13) were detected using the iPLEX assay (Sequenom, Inc). Results: Median follow-up for the entire cohort was 38.8 months. 118 were KRAS wildtype (WT), and 51 were KRAS MUT (45 G12, 5 G13, 1 K117N). The 3 year RFS was 48% [95%CI: 37-58%] for KRAS WT pts and 30% [15-44%] for MUT pts (p<0.01). OS at 3 years was 96% [88-98%] for KRAS WT and 80% [61-90%] for MUT pts (p=0.08). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in Table 1. The cumulative incidence of metastases to bone at 2 years was 0% and 13.7% in KRAS WT versus MUT pts (p<0.01), to brain 0% versus 4.6% for KRAS WT versus MUT (p=0.05), and to lung 27% versus 47.5% in KRAS WT versus MUT pts (p<0.01). Conclusions: In pts who have had liver resection followed by adjuvant therapy, those with KRAS MUT have a worse RFS and seemingly worse OS than those who are KRAS WT. Also, patients with KRAS MUT appear more likely to develop bone, brain, and lung metastases. Further investigation of a larger number of patients is warranted. [Table: see text]

Prognostic impact of K-RAS mutational status and primary tumor location in patients undergoing resection for colorectal cancer liver metastases: an update

2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Mutation Status

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

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.

The ALPPS Approach for Colorectal Liver Metastases: Impact of KRAS Mutation Status in Survival

2017 ◽  
Vol 35 (4) ◽  
pp. 303-310 ◽  
Author(s):  
Matteo Serenari ◽  
Fernando Andres Alvarez ◽  
Victoria Ardiles ◽  
Martin de Santibañes ◽  
Juan Pekolj ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Kras Mutation ◽  
Colorectal Liver Metastases ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals The ALPPS approach for colorectal liver metastases: impact of KRAS mutation status in survival

HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S654-S655
Author(s):  
M. Serenari ◽  
F. Alvarez ◽  
V. Ardiles ◽  
M. De Santibanes ◽  
J. Pekolj ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Kras Mutation ◽  
Colorectal Liver Metastases ◽  
Mutation Status ◽  
Kras Mutation Status

KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

2016 ◽  
Vol 24 (1) ◽  
pp. 264-271 ◽  
Author(s):  
Georgios A. Margonis ◽  
Kazunari Sasaki ◽  
Nikolaos Andreatos ◽  
Yuhree Kim ◽  
Katiuscha Merath ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Kras Mutation ◽  
Colorectal Liver Metastases ◽  
Surgical Margin ◽  
Mutation Status ◽  
Margin Width ◽  
Kras Mutation Status

scholarly journals The ALPPS approach for colorectal liver metastases: impact of KRAS mutation status in survival

HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S841
Author(s):  
M. Serenari ◽  
F. Alvarez ◽  
V. Ardiles ◽  
M. De Santibanes ◽  
J. Pekolj ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Kras Mutation ◽  
Colorectal Liver Metastases ◽  
Mutation Status ◽  
Kras Mutation Status

Retrospective cohort study on the safety and efficacy of bevacizumab for metastatic colorectal cancer patients: The HGCSG0801 study—Efficacy of KRAS mutational status.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 680-680 ◽  
Author(s):  
Susumu Sogabe ◽  
Satoshi Yuki ◽  
Hideyuki Hayashi ◽  
Hirohito Naruse ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Mutational Status ◽  
Kras Mutation Status

680 Background: Mutations of the KRAS gene were identified as a prognostic marker in metastatic colorectal cancer(mCRC). Previously reported data suggests that the longer overall survival (OS) observed with bevacizumab(BV) treatment in mCRC is independent of alterations in the KRAS mutation status. So we analyzed efficacy of bevacizumab combined chemotherapy in mCRC relative to KRAS mutation status. Methods: In the retrospective analysis(n=212) of patients treated with BV(HGCSG0801), additional statistical analyses were done with data from KRAS mutation analyses. The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine Progression-free survival(PFS) and OS. Log-rank test was used to compare with mutant or wild-type KRAS in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status was assessed in 88 patients (41.5%). Response rate was 58.9% with wild-type and 62.5% with mutant KRAS, that was not significant(p=0.823). The median Progression-free survival was 11.5 months with wild-type and 11.5 months with mutant KRAS, that was not significant(p=0.222). And median OS was 31.8 months with wild-type and 27.5 months with mutant KRAS, that was not significant(p=0.760) as well. Similar results were seen among patients with first-line therapy. Conclusions: Bevacizumab provides clinical benefit in patients with mCRC expressing either mutant or wild-type KRAS.

Influence of KRAS mutation on recurrence patterns in patients undergoing hepatic resection of colorectal metastases.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 398-398
Author(s):  
Nancy E. Kemeny ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Alexandra N. Gewirtz ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Liver Resection ◽  
Brain Metastases ◽  
Liver Metastases ◽  
Cumulative Incidence ◽  
Kras Mutation ◽  
Small Sample ◽  
Colorectal Metastases ◽  
Clinical Factors ◽  
Significant Difference ◽  
Recurrence Patterns

398 Background: There have been conflicting results about whether KRAS mutation influences outcome in patients (pts) with colorectal cancer. In pts who underwent liver resection, Karagkounis reported a worse recurrence and survival in KRAS mutated (MUT) patients (ASCO 2012, abs 3616). Methods: In 105 pts who underwent liver resection and received adjuvant (adj) hepatic arterial infusion and systemic chemotherapy and in whom KRAS data was available, we evaluated recurrence patterns and survival. Correlation between KRAS and clinical factors such as prior chemotherapy, post operative CEA, clinical risk score, and stage at diagnosis was evaluated using Fisher’s exact test and the Wilcoxon rank sum test. Kaplan-Meier methods were used to estimate median overall recurrence free survival (RFS) and overall survival (OS) at 4 years. Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adj therapy to bone, brain, lung and liver metastases separately. Results: Of 105 patients, 76 were KRAS wildtype (WT), and 29 were KRAS MUT (26-G12 and 3-G13). The median RFS was 26 months for KRAS WT pts and 15 months for KRAS MUT pts (p=0.08). OS at 4 years was 88% [95% CI: 78%-94%] for KRAS WT and 78% [95% CI: 57%-90%] for KRAS MUT pts (p= 0.15). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in the Table. The cumulative incidence of bone and brain metastases at 2 years was 0% and 0% in KRAS WT pts versus 16.4% [95% CI: 1.1%-31.7%] and 4.7% [95% CI: 0%-14.1%] in KRAS MUT pts (Table). There was no association between clinical factors and KRAS status. Conclusions: KRAS MUT pts appeared to have worse OS and RFS, although we were unable to show a significant difference between KRAS WT and MUT for OS and RFS. In addition, cumulative incidence of bone and brain metastases at 2 years appeared to be higher for KRAS MUT pts as compared to WT pts. Results are based on small sample size and further investigation is needed. [Table: see text]

Genomic biomarkers to determine survival in Multicenter Study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16119-e16119
Author(s):  
Meaghan Dendy Case ◽  
Anish Ghodadra ◽  
Paula M. Novelli ◽  
Vincent Wu ◽  
Suvranu Ganguli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastases ◽  
Kras Mutation ◽  
Colorectal Liver Metastases ◽  
Mutation Status ◽  
Neutrophil Lymphocyte Ratio ◽  
Patient Demographics ◽  
Y90 Radioembolization ◽  
Kras Mutation Status ◽  
Tumor Genotyping

e16119 Background: Assessment of the clinical outcomes and prognostic value of genomic mutations in colorectal liver metastases treated with Y90 radioembolization. Methods: Multi-institution retrospective study of patients who underwent Y-90 radioembolization treatment after tumor genotyping was completed for CRLM. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, tumor characteristics, pre- and post- treatment regimens, serum laboratory evaluation and overall survival were analyzed between patients with differing histopathologic and genomic status. Tumor genotyping was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 434 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 399 patients were available who had sufficient documented tumor profiling data. Average age at diagnosis was found to be 58.8 years for all patients (60.1% male, 39.9% female). Decreased survival post Y-90 treatment was shown in those patients with increased number of documented tumor mutations (n = 0,1 or ≥2 mutations: median OS 9.63 mos vs. 6.2 mos vs. 5.3 mos; p < 0.0001). Additionally, the median survival in patients with mutated BRAF was 5.0 months, as compared to 9.4 months in those patients with wild-type BRAF (p = 0.0009). Primary colon cancer sidedness was also shown to demonstrate significant difference in survival post-Y90 treatment with left sided primaries showing improved median overall survival (left = 7.5 mos vs. right = 6.3 mos; p = 0.04.) Patient demographics including gender, age and race were not shown to be significant in overall survival post-Y90 treatment (p-values > 0.05). Number of tumor mutations (p < 0.0001, HR = 1.69 CI: 1.39-2.05), BRAF status (p = 0.02, HR = 2.6 CI:1.20-4.9), primary sidedness (p = 0.01, HR = 0.65 CI:0.47-0.90), pre-treatment neutrophil-lymphocyte ratio (p = 0.04, HR = 1.42 CI: 1.02-1.98) and KRAS mutation status (p < 0.0001, HR = 1.81 CI: 1.45-2.26) all persisted as significant predictors of survival on multivariate analysis. Conclusions: Number of tumor mutations, BRAF mutation status, primary tumor sidedness, neutrophil-lymphocyte ratio and KRAS mutation status are all shown to be significant prognostic factors in patients with colorectal liver metastases receiving Y90 radioembolization.

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