Genotyping of tumor tissues to assess RAS and BRAF V600E mutations enables us to select optimal molecularly targeted therapies when considering treatment strategies for patients with metastatic colorectal cancer. Tissue-based genetic testing is limited by the difficulty of performing repeated tests, due to the invasive nature of tissue biopsy, and by tumor heterogeneity, which can limit the usefulness of the information it yields. Liquid biopsy, represented by circulating tumor DNA (ctDNA), has attracted attention as a novel method for detecting genetic alterations. Liquid biopsies are more convenient and much less invasive than tissue biopsies and are useful for obtaining comprehensive genomic information on primary and metastatic tumors. Assessing ctDNA can help track genomic evolution and the status of alterations in genes such as RAS, which are sometimes altered following chemotherapy. In this review, we discuss the potential clinical applications of ctDNA, summarize clinical trials focusing on RAS, and present the future prospects of ctDNA analysis that could change daily clinical practice.

Background/Aims: Endoscopic management by endoscopic sphincterotomy with or without plastic stents or fully covered self-expandable metallic stents (FCSEMSs) is widely accepted as the current standard of care for postoperative bile leaks. Biliary stents are placed across the papilla, not above the papilla. We investigated the safety and effectiveness of the bridge-and-seal technique for bile leaks by the placement of FCSEMS above the papilla. Methods: This was a retrospective study of FCSEMS placement above the papilla for bile leaks between October 2016 and July 2021. FCSEMS was placed above the papilla to bridge and seal the leak. The main outcome measures were the resolution of bile leaks and adverse events. Results: Seven patients with postoperative bile leaks underwent FCSEMS above the papilla. The locations of bile leaks were 1 cystic duct remnant; 2 intrahepatic bile duct; 1 hepatic duct; 2 common bile duct and 1 anastomosis. The technical success rate of FCSEMS placement was 100%, and resolution of bile leaks was achieved in five patients (71.4%). All the adverse events were observed after FCSEMS removal; as follows: 1 moderate cholangitis; 2 mild post-ERCP pancreatitis; and 1 mild remnant cholecystitis. Conclusions: FCSEMS placement above the papilla can be a treatment option for postoperative bile leaks.

Purpose: To investigate circulating tumor DNA (ctDNA) RAS mutant (MT) incidence before salvage-line treatment and the clinicopathological features and molecular biological factors associated with the efficacy of anti-epithelial growth factor receptor (EGFR) monoclonal antibody (mAb) rechallenge for tissue RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC). Methods: This multi-institutional retrospective observational study included 74 patients with mCRC with tissue RAS/BRAF WT refractory to first-line chemotherapy containing anti-EGFR mAb. ctDNA RAS status was assessed using the OncoBEAM™ RAS CRC Kit. We explored the clinicopathological features associated with ctDNA RAS status and the factors related to anti-EGFR mAb rechallenge efficacy in multivariate Cox proportional hazard regression. Results: The incidence of RAS MT in ctDNA was 40.5% (30/74), which was associated with primary tumor resection (P = 0.016), liver metastasis (P < 0.001), and high tumor marker levels (P < 0.001). Among the 39 patients treated with anti-EGFR mAb rechallenge, those with ctDNA RAS WT showed significantly longer progression-free survival (PFS) than those with ctDNA RAS MT (median 4.1 vs. 2.7 months, hazard ratio [HR] = 0.39, P = 0.045). Patients who responded to first-line anti-EGFR mAb showed significantly longer PFS (HR = 0.21, P = 0.0026) and overall survival (OS) (HR = 0.23, P = 0.026) than those with stable disease. Conclusions: The incidence of ctDNA RAS MT mCRC was 40.5%, which was associated with liver metastases and high tumor volumes. Anti-EGFR mAb rechallenge may be effective for patients with mCRC who responded to first-line chemotherapy containing anti-EGFR mAb. No patients with RAS MT in ctDNA responded to anti-EGFR mAb rechallenge.

Shimozaki K, et al. J Gastric Cancer. 2023 Oct;23(4):609-621. https://doi.org/10.5230/jgc.2023.23.e41