Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies worldwide [1, 2]
CRC patients being considered for EGFR monoclonal antibody (mAb) therapy should have the confirmed absence of relevant
In patients with stage II and III CRC who underwent curative resection followed by standard adjuvant chemotherapy (FOLFOX or FOLFIRI), KRAS mutation was significantly associated with poor disease-free survival (DFS), while the BRAF mutation was not associated with DFS [7]
Summary
Colorectal cancer (CRC) is one of the most common malignancies worldwide [1, 2]. In the past decade, the 5-year survival rate for CRC patients has improved mainly due to the development of new drug combinations and targeted molecular agents. In patients with stage II and III CRC who underwent curative resection followed by standard adjuvant chemotherapy (FOLFOX or FOLFIRI), KRAS mutation was significantly associated with poor disease-free survival (DFS), while the BRAF mutation was not associated with DFS [7]. 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. Patient clinicopathologic features and RAS/BRAF gene mutation status were evaluated by survival analysis for disease-free survival (DFS) and progression-free survival (PFS). Mutations of RAS/BRAF had no significant impact on DFS after surgery (hazard ratio (HR), 1.205; 95% CI, 0.618 to
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