KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer

• Published in: Molecular oncology Vol. 9; no. 7; pp. 1341 - 1347
• Main Authors: Deng, Yanhong, Wang, Li, Tan, Shuyun, Kim, George P., Dou, Ruoxu, Chen, Dianke, Cai, Yue, Fu, Xinhui, Wang, Lei, Zhu, Jun, Wang, Jianping
• Format: Journal Article
• Language: English
• Published: United States Elsevier B.V 01.08.2015; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Adjuvant chemotherapy; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biomarkers; Cancer; Cancer therapies; Carcinoembryonic antigen; Chemotherapy; Cohort Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Cytotoxicity; Deoxyribonucleic acid; Disease; DNA; Family medical history; Female; Fluorouracil - administration & dosage; FOLFOX; Genes, ras; Hospitals; Humans; K-Ras protein; KRAS; Leucovorin - administration & dosage; Male; Medical prognosis; Middle Aged; Multivariate analysis; Mutation; Organoplatinum Compounds - administration & dosage; Patients; Prognosis; Research Paper; Research Papers; Studies; Surgery; Survival analysis; Tumors; Young Adult; Adjuvant chemotherapy; KRAS; FOLFOX; Colorectal cancer
• ISSN: 1574-7891; 1878-0261
• DOI: 10.1016/j.molonc.2015.03.006

The KRAS gene frequently mutates in colorectal cancer (CRC). Here we investigated the prognostic and predictive role of KRAS mutation in patients with stage II or III CRC. A consecutive cohort of patients with stage II or III CRC from a single center database was studied. The association between KRAS status, adjuvant FOLFOX therapy, and 3-year disease-free survival (3-y DFS) was analyzed. Of our 433 patients, 166 (38.3%) exhibited the KRAS mutation. Among the 190 patients who did not receive adjuvant therapy, those with KRAS mutation tumors had a worse 3-y DFS (hazard ratio [HR], 1.924; 95% confidence interval [CI], 1.078–3.435; P = 0.027). Among patients who received adjuvant chemotherapy, KRAS mutation was not correlated with worse 3-y DFS (HR, 1.083; 95% CI, 0.618–1.899; P = 0.781). Adjuvant chemotherapy improved 3-y DFS only among patients with KRAS mutant tumors (78.0% vs 69.2%) on multivariate analysis adjusted for age, stage, grade, site, vessel invasion, and carcinoembryonic antigen level (HR, 0.454; 95% CI, 0.229–0.901; P = 0.024). In contrast, there was no benefit of adjuvant chemotherapy in the KRAS wild-type group (84.3% vs 82.0%). KRAS mutation indicates poor prognosis. FOLFOX adjuvant chemotherapy benefits patients with stage II or III colorectal cancer with KRAS mutant tumors and is worth further investigation. •The results showed patients with KRAS mutant tumors have poorer survival than those with KRAS wild type tumors, but after adjuvant FOLFOX chemotherapy, the patients' prognosis gets improved.•Only patients with KRAS mutant tumors benefit from adjuvant chemotherapy in colorectal cancer.•It indicated that patients with KRAS mutant tumors, oxaliplatin-based adjuvant therapy must be guaranteed.