title: KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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%).
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Oncology, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. Electronic address: dengyanh@mail.sysu.edu.cn.
authors: Yanhong
authors: Y
authors: Deng
authors: Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors: Li
authors: L
authors: Wang
authors: Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Shuyun
authors: S
authors: Tan
authors: Department of Hematology/Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, 32224, USA.
authors: George P
authors: GP
authors: Kim
authors: Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Ruoxu
authors: R
authors: Dou
authors: Department of Medical Oncology, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Dianke
authors: D
authors: Chen
authors: Department of Medical Oncology, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Yue
authors: Y
authors: Cai
authors: Department of Molecular Diagnosis, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Xinhui
authors: X
authors: Fu
authors: Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China.
authors: Lei
authors: L
authors: Wang
authors: Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors: Jun
authors: J
authors: Zhu
authors: Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. Electronic address: wangjpgz@126.com.
authors: Jianping
authors: J
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D011905:Genes, ras; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
keywords: Adjuvant chemotherapy; Colorectal cancer; FOLFOX; KRAS