RAS/BRAF Circulating Tumor DNA Mutations as a Predictor of Response to First-Line Chemotherapy in Metastatic Colorectal Cancer Patients

• Published in: Canadian journal of gastroenterology & hepatology Vol. 2018; no. 2018; pp. 1 - 10
• Main Authors: Yan, Rui, Yu, Yang, Jin, Mulan, Cheng, Gang, An, Guangyu, Jiang, Zhi, Rao, Guanhua, Li, Lei, Yu, Pan, Weygant, Nathaniel, Ge, Yang, Zang, Wanchun, Yao, Jiannan, He, Linjia
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2018; Hindawi; Hindawi Limited
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Cancer genetics; Cancer metastasis; Cancer patients; Cancer therapies; Cancer treatment; Care and treatment; Chemotherapy; China; Circulating Tumor DNA - genetics; Cohort Studies; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Comparative analysis; Deoxyribonucleic acid; Development and progression; Disease-Free Survival; DNA; EDTA; Female; Gene mutation; Genes; Genetic aspects; Genetic testing; Humans; Kaplan-Meier Estimate; Male; Medical research; Metastasis; Middle Aged; Molecular Targeted Therapy - methods; Mutation; Neoplasm Invasiveness - pathology; Neoplasm Metastasis; Neoplasm Staging; Oncology; Patients; Plasma; Polymerase Chain Reaction - methods; Prognosis; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Retrospective Studies; Risk Assessment; Statistical analysis; Statistics, Nonparametric; Surgery; Survival Analysis; Treatment Outcome; Tumors; China; Beijing China; United States > US
• ISSN: 2291-2789; 2291-2797
• DOI: 10.1155/2018/4248971

Background. Since circulating tumor DNA (ctDNA) offers clear advantages as a minimally invasive method for tumor monitoring compared with tumor tissue, we aimed to evaluate genotyping ctDNA using a next-generation sequencing- (NGS-) based panel to identify the prognostic value of mutation status in metastatic colorectal cancer (mCRC) patients with primary tumor resected and with subsequent lines of treatment in this study. Methods. 76 mCRC patients treated in Beijing Chao-Yang Hospital from 2011 to 2017 were enrolled. Genotyping of RAS/BRAF in tumor tissue and ctDNA was determined by ARMS PCR and with a 40-gene panel using NGS, respectively. Patient clinicopathologic features and RAS/BRAF gene mutation status were evaluated by survival analysis for disease-free survival (DFS) and progression-free survival (PFS). Results. Among 76 patients, KRAS distributions were not significantly correlated with any clinicopathologic features. The concordance between tumor tissue and ctDNA KRAS mutation was 81.25%. Mutations of RAS/BRAF had no significant impact on DFS after surgery (hazard ratio (HR), 1.205; 95% CI, 0.618 to 2.349; P = 0.5837 ) but prognosticated poorer PFS in subsequent first-line therapy (HR, 3.351; 95% CI, 1.172 to 9.576; P = 0.024 ). Conclusion. ctDNA was comparable with tumor tissue for mutation detection. RAS/BRAF mutations detected in ctDNA predict a worse PFS in mCRC patients with first-line chemotherapy. Our results provide support for the prognostic value of RAS/BRAF ctDNA mutation detection in mCRC patients.