Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Prognostic value of methylator phenotype in stage III colon cancer treated with oxaliplatin-based adjuvant chemotherapy

Abstract : Purpose: There are conflicting results concerning the prognostic value of the CpG island methylator phenotype (CIMP) in non-metastatic colon cancer (CC) patients. We studied this phenotype in stage III CC characterized for mismatch repair (MMR), RAS and BRAF status and treated with adjuvant FOLFOX-based regimen. Experimental Design: Tumor samples of 1907 patients enrolled in the PETACC-8 adjuvant phase 3 trial were analyzed. The method used was methylation-specific PCR where CIMP+ status was defined by methylation of at least three of the five following genes: IGF2, CACNA1G, NEUROG1, SOCS1, and RUNX3. Association between CIMP status and overall survival (OS), disease-free survival (DFS), and survival after recurrence (SAR), was assessed by Cox model adjusted for prognostic factors and treatment arm (FOLFOX4 ± cetuximab). Results: CIMP status was successfully determined in 1867 patients (97.9%): 275 (14.7%) tumors were CIMP+. Compared to CIMP- patients, CIMP+ patients were more frequently older (p=0.002), females (p=0.04), with right-sided (p<0.0001), grade 3-4 (p<0.0001), pN2 (p=0.001), dMMR (p<0.0001), BRAF mutated (p<0.0001), and RAS wild-type (p<0.0001) tumors. In multivariate analysis, CIMP+ status was associated with shorter OS (HR: 1.46; 95%CI 1.02 - 1.94; p=0.04) and SAR (HR: 1.76; 95%CI 1.20 - 2.56; p<0.0004); but not DFS (HR: 1.15 95%CI 0.86 - 1.54; p=0.34). A non-significant trend of detrimental effect of cetuximab was observed in patients with CIMP+ tumors for OS, DFS, and SAR. Conclusions: In a large cohort of well-defined stage III CC patients, CIMP+ phenotype is associated with a shorter OS and SAR but not to DFS.
Keywords : oncology
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01824620
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 27 juin 2018 - 14:15:57
Dernière modification le : mercredi 19 août 2020 - 12:08:21

Lien texte intégral

Identifiants

Citation

Claire Gallois, Julien Taïeb, Delphine Le Corre, Karine Le Malicot, Josep Tabernero, et al.. Prognostic value of methylator phenotype in stage III colon cancer treated with oxaliplatin-based adjuvant chemotherapy. Clinical Cancer Research, American Association for Cancer Research, 2018, 24 (19), pp.4745-4753. ⟨10.1158/1078-0432.CCR-18-0866⟩. ⟨hal-01824620⟩

Partager

Métriques

Consultations de la notice

343