E210: Circulating Tumor DNA in Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma

Twenty-three patients were included, most of whom underwent resection (n=17, 74%), transplant (n=3, 13%) or ablation (n=3, 13%). Median and maximum follow-up were 16 and 45 months respectively. Most patients had positive post-operative ctDNA (n=20, 87%). There was a trend toward reduced recurrence-free survival in patients with positive post-operative ctDNA (13.1 vs. 9.4 months), though this was not statistically significant (Fig. 1A). In terms of post-operative TMB, 14 (60.8%) had detectable TMB versus not detectable (n=9, 39.1%).

Fourteen (61%) patients experienced recurrence, most of whom were post-operative ctDNA+ (n=13, 93%). In patients with CCA recurrence, the dominant mutations were TP53 (31%), ARID1A (31%), and KIT (23%) versus ATM (57%) in patients did not have recurrence (Fig. 1B). Four (11%) patients had sequential testing, all of whom had positive ctDNA pre- and post-operatively (+/+) (Fig. 1C). Three patients showed partial or near complete clearance of their pre-operative mutations (#1, 3-4) whereas one patient showed no change in mutational profile with resection (#2) (Fig. 1C). One patient with sequential testing experienced CCA recurrence; despite near clearance of pre-operative mutations, acquired mutations in KRAS, ARID1A, and CDK12 were noted post-operatively (Fig. 1C).

Conclusions: The high rate of identifiable post-operative ctDNA is striking after curative intent surgery for CCA, and most patients who developed recurrence had positive post-operative ctDNA. Given the high rate of post-operative ctDNA positivity, use of individualized somatic alterations, rather than positivity vs. negativity status alone, may need to be explored for therapy-decision making and tailored treatment design. Further larger-scale studies are needed to investigate the utility of ctDNA in CCA patients.