Monitoring of Dynamic Changes and Clonal Evolution in Circulating Tumor DNA From Patients With -Mutated Cholangiocarcinoma Treated With Isocitrate Dehydrogenase Inhibitors.

Purpose: mutations occur in about 30% of patients with cholangiocarcinoma. Analysis of mutations in circulating tumor DNA (ctDNA) can be performed by droplet digital polymerase chain reaction (ddPCR). The analysis of ctDNA is a feasible approach to detect mutations.

Methods: We isolated ctDNA from the blood of patients with -mutated advanced cholangiocarcinoma collected at baseline, on therapy, and at progression to isocitrate dehydrogenase (IDH) inhibitors.

Results: Of 31 patients with (n = 26) or mutations (n = 5) in the tumor, mutations were detected in 84% of ctDNA samples analyzed by ddPCR and in 83% of ctDNA samples analyzed by next-generation sequencing (NGS). Patients with a low variant allele frequency of ctDNA detected by NGS at baseline had a longer median time to treatment failure compared to patients with high variant allele frequency of ctDNA (3.6 1.5 months; = .008). Patients with a decrease in -mutated ctDNA on therapy by ddPCR compared with no change/increase had a trend to a longer median survival ( = .07). Most frequent emergent alterations in ctDNA by NGS at progression were (n = 3) and mutations (n = 3).

Conclusion: Detection of mutations in ctDNA in patients with advanced cholangiocarcinoma is feasible, and dynamic changes in ctDNA can correspond with the clinical course and clonal evolution.