scholarly journals Prognostic value of microsatellite instability (MSI)/deficient mismatch repair (MMR) and BRAFV600E mutation in recurring stage III colon cancer: insights from an ACCENT pooled analysis of seven adjuvant chemotherapy trials

2020 ◽  
Vol 3 ◽  
pp. 113-113
Author(s):  
Anuratha Sakthianandeswaren ◽  
Dmitri Mouradov ◽  
Oliver M. Sieber
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Prognostic Value ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Brafv600e Mutation ◽  
Stage Iii Colon Cancer ◽  
Deficient Mismatch Repair

Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer

Cancer ◽  
2020 ◽  
Vol 126 (18) ◽  
pp. 4136-4147
Author(s):  
Walid L. Shaib ◽  
Katerina M. Zakka ◽  
Renjian Jiang ◽  
Ming Yan ◽  
Olatunji B. Alese ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Survival Outcome ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Deficient Mismatch Repair

scholarly journals Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials

2020 ◽  
pp. JCO.20.01600
Author(s):  
Romain Cohen ◽  
Julien Taieb ◽  
Jack Fiskum ◽  
Greg Yothers ◽  
Richard Goldberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Prognostic Value ◽  
Randomized Clinical Trials ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Cox Models ◽  
Stage Iii Colon Cancer ◽  
Similar Survival

PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.

scholarly journals Role of Deficient DNA Mismatch Repair Status in Patients With Stage III Colon Cancer Treated With FOLFOX Adjuvant Chemotherapy

JAMA Oncology ◽  
2018 ◽  
Vol 4 (3) ◽  
pp. 379 ◽  
Author(s):  
Aziz Zaanan ◽  
Qian Shi ◽  
Julien Taieb ◽  
Steven R. Alberts ◽  
Jeffrey P. Meyers ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Stage Iii ◽  
Dna Mismatch ◽  
Stage Iii Colon Cancer ◽  
Mismatch Repair Status

scholarly journals Prognostic Value of Methylator Phenotype in Stage III Colon Cancer Treated with Oxaliplatin-based Adjuvant Chemotherapy

2018 ◽  
Vol 24 (19) ◽  
pp. 4745-4753 ◽  
Author(s):  
Claire Gallois ◽  
Julien Taieb ◽  
Delphine Le Corre ◽  
Karine Le Malicot ◽  
Josep Tabernero ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Value ◽  
Stage Iii ◽  
Stage Iii Colon Cancer ◽  
Methylator Phenotype

Microsatellite instability status as a predictive marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 493-493 ◽  
Author(s):  
A. Zaanan ◽  
J. Flejou ◽  
J. Emile ◽  
P. Validire ◽  
C. Louvet ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcome ◽  
Microsatellite Instability ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Free Survival ◽  
Stage Iii Colon Cancer

493 Background: The addition of oxaliplatin to 5-fluorouracil (5-FU; FOLFOX regimen) was demonstrated to improve the adjuvant treatment of stage III colon cancer. For patients with microsatellite instability (MSI) tumors, several studies suggested a lack of benefit from 5-FU adjuvant chemotherapy but very little data are available regarding FOLFOX adjuvant therapy. The aim of this study was to further assess the value of MSI status as a marker of clinical outcome from FOLFOX adjuvant chemotherapy in stage III colon cancer. Methods: This multicentric retrospective study included 223 unselected patients with stage III colon cancer treated by FOLFOX adjuvant chemotherapy between 2003 and 2007. MSI status was determined by immunohistochemistry as the absence of MLH1, MSH2 or MSH6 expression. Disease-free survival (DFS) and relapse-free survival (RFS) were analyzed according to the MSI status using Kaplan Meier method and compared by log-rank test. Results: Twenty three tumors (10.3%) were MSI. The rate of 3-year DFS was 88.6% and 76.6% for MSI and MSS groups, respectively (HR=0.64; 95% CI, 0.25 to 1.60; P=0.34). The rate of 3-year RFS was 88.6% and 76.7% for MSI and MSS groups, respectively (HR=0.52; 95% CI, 0.20 to 1.30; P=0.18). Conclusions: A trend toward longer survival was observed for patients with MSI tumors compared with those with MSS tumors but the differences in survival were not significant. Interestingly, DFS at 3-years of patients with stage III MSI tumors treated by FOLFOX was higher in our series (88.6%) than in the largest study published for patients treated by 5-FU-based adjuvant chemotherapy (around 67.5%) or surgery alone (around 62.5%) (Sargent et al, JCO 2010). These observations suggest that adding oxaliplatin to 5-FU re-establishes a benefit of adjuvant treatment in the stage III MSI population. These results should be confirmed by analyzing materials of previously completed trials comparing FOLFOX to 5-FU such as the MOSAIC study. [Table: see text]

Duration of FOLFOX adjuvant chemotherapy in high-risk stage II and stage III colon cancer with deficient DNA mismatch repair.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4075-4075
Author(s):  
Zehua Wu ◽  
Huabin Hu ◽  
Chao Wang ◽  
Yan Huang ◽  
Yanhong Deng
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Therapy Group ◽  
Stage Ii ◽  
Stage Iii ◽  
Dna Mismatch ◽  
Stage Iii Colon Cancer

4075 Background: In the IDEA collaboration, noninferiority was not confirmed for 3 months versus 6 months of FOLFOX adjuvant chemotherapy among patients with high-risk stage II and stage III colon cancer (CC). Patients with deficient DNA mismatch repair (dMMR) have a good prognosis, but for whom, whether limiting the duration of adjuvant therapy will compromise oncologic outcomes remains undefined. We evaluated the impact of 3 months of FOLFOX adjuvant chemotherapy or surgery alone in comparison with 6 months of FOLFOX on disease-free survival (DFS) in dMMR CC patients. Methods: This retrospective study included all consecutive patients who underwent curative surgical resection for high-risk stage II or III dMMR CC between May, 2011 and July, 2019. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Results: A total of 242 dMMR CC patients were included (43.4% high-risk stage II, 56.6% stage III). The patients received 6 months of FOLFOX adjuvant chemotherapy (n = 66; median cycles [rang] = 12 [10-12]), 3 months of FOLFOX (n = 87; median cycles [rang] = 6 [4-8]), or surgery alone (n = 89). Three groups were generally well balanced, although more patients with stage III were in the 6-month therapy group (74.2%), compared with the 3-month therapy group (57.5%) and the surgery alone group (42.7%). As compared with 6 months of FOLFOX adjuvant chemotherapy in the overall population, 3 months therapy reduced DFS in multivariable analysis (HR, 2.78; 95CI, 1.18 to 6.47; P = 0.02), similar to surgery alone (HR, 2.30; 95CI, 0.99 to 5.38; P = 0.05). In the subgroup analysis, a therapy duration of 6 months was statistically superior to a duration of 3 months only in the patients with stage III, with a 3-year rate of DFS of 86.2% versus 70.8% (HR, 3.06; 95% CI, 1.14 to 8.19; P = 0.026). Conclusions: This study supports the 6-month duration of FOLFOX adjuvant chemotherapy in stage III dMMR CC.

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