Background:
Advanced biliary cancers or cholangiocarcinomas (CCAs) are an important cause of cancer related mortality worldwide. Most patients present at an incurable stage and are not suitable for surgery. Prognosis for these patients remains poor with median survival of 1-2 years with current palliative chemotherapy regimens. Recent novel therapeutic strategies have been developed on the basis of molecular and genetic characteristics that are present within subsets of patients with ABC. Molecular testing has been recommended to be integrated into standard of care for the diagnosis and management of these patients. One of the major barriers to this is the challenge of obtaining adequate quality tissue material suitable for molecular analysis.

Methods:
A prospective, multi-centre cohort study was designed to perform targeted DNA/RNA sequencing on 50 patients undergoing diagnostic EUS or ERCP with cholangioscopic biopsies for advanced cholangiocarcinoma (CCA). These patients were typically assessed through multi-disciplinary meeting as inoperable or be returning for standard of care stent changes. Molecular testing was performed using the TSO-500 gene panel and the results were reviewed in a Molecular Tumour Board (MTB) to see if any targetable therapeutic options are available to the patients. To date all of these samples have been recruited from the one centre (Monash Health) with a second site recently opened.

Results:
To date 29 patients have been recruited for the study (Figure 1 – patient demographics). One patient has withdrawn due to a revised diagnosis. 21 patients have had DNA/RNA extraction and subsequent sequencing. 7 further patients are awaiting sequencing to be completed. CMP was completed on all 21 patients. 15 patients were found to have mutations, 6 patients had no mutations which may reflect sampling error or potentially no mutations of relevance. 3 patients were found to have potentially targetable mutations including a ERBB (HER-2), BRAF V600E mutation and a high TMB (Figure 2) An interim analysis suggests that cholangioscopic biopsies (Spybites) detected mutations in 8/9 (89%) whereas only 7/12 EUS FNB samples (58%) found mutations.

Conclusion:
These are interim results of a real-world study assessing the feasibility and utility for endoscopic biopsies (either via EUS or cholangioscopy) as a source of tissue material for comprehensive molecular analysis in inoperable CCAs. Direct vision of the cholangioscopic biopsies appears to provide more likely chance of success in these patients compared to an additional separate pass of the FNB needle using EUS.

Figure 1 Patient Demographics ACME ABC (interim results)

Owen McKay

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