Clinical Implication of KRAS Mutation Variants in Patients With Resected Colon Cancer

2022 ◽  
Vol 2 (1) ◽  
pp. 78-83
Author(s):  
JIN HO BAEK ◽  
JUHYUNG KIM ◽  
DONG WON BAEK ◽  
EUNHYE CHANG ◽  
HYE JIN KIM ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Kras Mutation ◽  
Disease Free Survival ◽  
Exon 2 ◽  
Mutation Status ◽  
Free Survival ◽  
Disease Free ◽  
Kras Mutation Status ◽  
Codon 61

Aim: This study evaluated the clinical implication of KRAS proto-oncogene, GTPase (KRAS) mutation variants in patients with resected colon cancer (CC). Patients and Methods: We retrospectively reviewed 482 patients diagnosed with CC who underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The inclusion criteria were: Pathologically diagnosed with primary CC; stage I-III CC according to the 7th edition of American Joint Committee on Cancer staging system; and with available test results for KRAS mutation status. In total, 345 patients met these criteria and were included in this study. Results: Among the 345 patients, 140 (40.6%) exhibited KRAS mutations, with their incidences as follows: 90/140 (64.3%) in exon 2 codon 12, 37/140 (26.4%) in exon 2 codon 13, 1/140 (0.1%) in exon 3 codon 59, 7/140 (5.0%) in exon 3 codon 61, and 5/140 (3.6%) in exon 4 codon 146. KRAS mutation status was not a significant prognostic factor for disease-free survival or overall survival. Although there were no significant differences in survival between patients with exon 2 codon 12 and exon 2 codon 13 mutations, poorer disease-free survival (p=0.085) and overall survival (p=0.005) were seen in those with exon 3 codon 61 mutation than in others. Conclusion: KRAS mutation status was not correlated with survival, but exon 3 codon 61 mutation might be a factor for poor prognosis in patients after resection of CC.

Re-Evaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials

2021 ◽  
Author(s):  
Jun Yin ◽  
Mohamed E Salem ◽  
Jesse G Dixon ◽  
Zhaohui Jin ◽  
Romain Cohen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Surrogate Endpoint ◽  
Free Survival ◽  
A Value ◽  
Deficient Mismatch Repair ◽  
Disease Free

Abstract Background Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. Methods Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. Results Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. Conclusion Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

Endpoints in adjuvant trials: A systematic review of the literature in colon cancer and proposed definitions for future trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4018-4018
Author(s):  
M. E. Buyse ◽  
K. J. Punt ◽  
C. H. Köhne ◽  
P. Hohenberger ◽  
R. Labianca ◽  
...  
Keyword(s):  
Systematic Review ◽  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Review Of The Literature ◽  
Free Survival ◽  
Medical Oncologists ◽  
Starting Point ◽  
Definition Of ◽  
Disease Free

4018 Background: Disease-free survival (DFS) is the primary endpoint of most trials testing adjuvant treatments. However many other endpoints are used. There is much confusion about these endpoints since different definitions were used among trials, or no definitions were provided at all. Moreover there is no consensus on either the definition of each endpoint or on the most relevant among these endpoints. This creates difficulties when comparing the results of various trials. Methods: Adjuvant trials in colon cancer were used as a model. A systematic review was performed on published adjuvant studies in colon cancer from 1997–2006, and the definitions of endpoints other than overall survival (OS) were recorded. A panel of medical oncologists, surgical oncologists, and a statistician, all with expertise in randomised trials in colorectal cancer, aimed to reach consensus on the definition of the various endpoints as well as to select the most relevant among these. Results: A total of 52 studies were identified. In addition to overall survival 8 other endpoints were used, and both the definition of these endpoints as well as the starting point differed considerably among these studies. No definition was provided for the endpoint in 19 (37%) studies and for the starting point in 30 (58%) studies. The panel reached consensus on the definition of each endpoint ( table ), and agreed that DFS, defined as the time from randomisation to any event irrespective of cause was considered to be the most relevant endpoint for adjuvant studies. The date of randomisation was considered to be the most appropriate starting point. Conclusions: The proposed guideline will help in the design of future adjuvant studies in colon cancer, and will achieve the uniformity required to facilitate cross-study comparisons. It may serve as a model for adjuvant studies in other solid tumors. [Table: see text] No significant financial relationships to disclose.

Overall survival (OS) and updated disease-free survival (DFS) results of the NSABP C-08 trial assessing bevacizumab (B) in stage II and III colon cancer.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3508-3508 ◽  
Author(s):  
C. J. Allegra ◽  
G. A. Yothers ◽  
M. J. O'Connell ◽  
S. Sharif ◽  
N. J. Petrelli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Cochrane systematic review and meta-analysis of adjuvant chemotherapy for stage II colon cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3548-3548
Author(s):  
Brandon Matthew Meyers ◽  
Humaid Obaid Al-Shamsi ◽  
Alvaro Tell Figueredo
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Cochrane Systematic Review ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

3548 Background: Colon cancer is potentially curable by surgery in the early stages of the disease. Adjuvant chemotherapy improves disease-free and overall survival in patients with stage III disease, but the magnitude of benefit in stage II colon cancer is less clear. A previous Cochrane systematic review and meta-analysis (SR/MA) found improved disease-free, but not overall survival (Figueredo et al., 2008). An updated SR/MA was performed to determine the effects of adjuvant chemotherapy on disease-free and overall survival in patients with stage II colon cancer. Methods: Relevant databases (MEDLINE, EMBASE, and Cochrane) were independently searched by all authors, using the same search strategy employed in the original study (1/1988 to 9/2012). Randomized trials containing data on stage II colon cancer patients undergoing adjuvant 5-fluorouracil (5FU) chemotherapy versus observation were included. Pooled results were expressed as hazard ratios (HR) whenever possible, or risk ratios (RR), with 95% confidence intervals (95%CI) using a random effects model. Results: Seven studies were identified, and included in the final SR/MA. Six of the 7 studies were included in the disease-free survival analysis (n=4587). Adjuvant 5FU was associated with better disease-free survival (RR 0.84 (95%CI 0.75-0.94)). All 7 studies (n=5353) were included in the overall survival analysis showing an improvement with adjuvant 5FU (HR 0.87 (95%CI 0.78-0.97)). There was no evidence of heterogeneity across the studies (I2 = 0% for all analyses). Conclusions: In stage II colon cancer, adjuvant 5FU chemotherapy statistically improves both disease-free and overall survival. Our SR/MA demonstrates, for the first time, an overall survival advantage with adjuvant chemotherapy in stage II colon cancer.

Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

2004 ◽  
Vol 22 (16) ◽  
pp. 3395-3407 ◽  
Author(s):  
Alvaro Figueredo ◽  
Manya L. Charette ◽  
Jean Maroun ◽  
Melissa C. Brouwers ◽  
Lisa Zuraw
Keyword(s):  
Systematic Review ◽  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Stage Ii Colon Cancer ◽  
Disease Free

Purpose To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy? Methods A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation. Results Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07). Conclusion There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

scholarly journals Neutrophil-to-lymphocyte ratio has limited predictive value for determining outcomes in perforated colon cancer: a propensity score analysis.

2020 ◽  
Author(s):  
Chunyi Wu ◽  
Jy-Ming Chiang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Jinn-Shiun Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Disease Free Survival ◽  
Neutrophil To Lymphocyte Ratio ◽  
Free Survival ◽  
Lymphocyte Ratio ◽  
Disease Free ◽  
Perforated Colon

Abstract Background: The neutrophil-to-lymphocyte ratio is a significant prognostic marker in resectable colorectal cancer; however, there are no equivalent findings for perforated colon cancer. Using our colorectal cancer database, we retrospectively analyzed the data from 1995 to 2015 to determine whether the preoperative neutrophil-to-lymphocyte ratio is associated with survival outcomes in patients with perforated colon cancer.Methods: One-to-one propensity score matching was applied to minimize the difference between the high (>5) and low (≤5) neutrophil-to-lymphocyte ratio groups. Clinicopathological factors, long-term overall survival, and disease-free survival were analyzed and compared between the two groups. The primary outcomes were overall survival and disease-free survival.Results: Before propensity score matching, the high neutrophil-to-lymphocyte ratio group had a significantly higher prevalence of leukocytosis (low vs. high neutrophil-to-lymphocyte ratio groups: 12 [12.9%] vs. 46 [59.7%], p<0.001), lower serum albumin levels (low vs. high neutrophil-to-lymphocyte ratio groups: 30 [32.3%] vs. 42 [54.5%], p=0.003), and a higher emergent operation rate (low vs. high neutrophil-to-lymphocyte ratio groups: 5 [5.4%] vs. 20 [26.0%], p<0.001). After one-to-one propensity score matching, the groups comprised 41 patients each; none of the parameters were significantly different between the two groups. The mean follow-up period was 76.3 months. The 5-year overall survival (p=0.637) and disease-free survival (p=0.827) rates were not significantly different between the high and low neutrophil-to-lymphocyte ratio groups.Conclusions: The neutrophil-to-lymphocyte ratio has limited predictive value for determining outcomes in patients with perforated colon cancer.

scholarly journals The prognostic value of Immunoscore in patients with cancer: A pooled analysis of 10,328 patients

2020 ◽  
Vol 35 (3) ◽  
pp. 3-13 ◽  
Author(s):  
Xingxia Zhang ◽  
Jie Yang ◽  
Liang Du ◽  
Yong Zhou ◽  
Ka Li
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Disease Specific Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Disease Free ◽  
Disease Specific

Objectives: Over the past decade, some publications have reported that Immunoscore was associated with the prognosis of several cancers. To better understand this issue, we conducted this pooled analysis. Methods: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from their inceptions to 15 May 2019 to identify relevant articles. The pooled hazard ratio (HR) and 95% confidence interval (CI) was estimated for overall survival, disease-free survival, and disease-specific survival. Results: A total of 26 cohort studies with 10,328 patients involving eight cancer specialties were evaluated mainly by the consensus Immunoscore. The pooled analysis indicated that a lower Immunoscore was associated with a poor overall survival (HR 2.23, 95% CI 1.58, 2.70), disease-free survival (HR 2.40, 95% CI 1.96, 2.49), and disease-specific survival (HR 2.81, 95% CI 2.10, 3.77) for all cancers. The same convincing results were found in colorectal cancer, gastric cancer, and non-small cell lung cancer (especially the consensus Immunoscore for colon cancer). In five other types of cancer the results were similar, but the sample sizes were limited. Conclusions: These findings support that Immunoscore is significantly associated with the prognosis of patients with cancer. It provides a reliable estimate of the risk of recurrence in patients with colon cancer. However, more high-quality studies are necessary to assess the prognostic value of Immunoscore in non-colon cancers.

Association of mucin production and survival in colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Mucin Production ◽  
Kaplan Meier ◽  
The Relationship ◽  
Disease Free

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.

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