Yanhong Deng1, Li Wang2, Shuyun Tan3, George P Kim4, Ruoxu Dou3, Dianke Chen5, Yue Cai5, Xinhui Fu6, Lei Wang3, Jun Zhu2, Jianping Wang7. 1. Department of Medical Oncology, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. Electronic address: dengyanh@mail.sysu.edu.cn. 2. 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. 3. Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. 4. Department of Hematology/Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, 32224, USA. 5. Department of Medical Oncology, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. 6. Department of Molecular Diagnosis, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. 7. Department of Colorectal Surgery, Gastrointestinal Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, PR China. Electronic address: wangjpgz@126.com.
Abstract
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
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