114P - Prospective longitudinal tumor-informed ctDNA in resectable biliary tract cancers

Background

Circulating tumor DNA (ctDNA) is an emerging strategy to define minimal residual disease (MRD) in resected cancers. Data in biliary tract cancers (BTC) is limited. We describe a prospective evaluation of ctDNA as part of a feasibility study of multi-platform profiling of resected BTC (NCT04561453).

Methods

We conducted a prospective multi-platform profiling study for resectable BTC from 2020 to 2023, which included tumor-informed ctDNA testing (Signatera^TM, Natera USA) obtained pre-operatively, within 6 weeks post-operatively prior to adjuvant therapy (MRD detection) and longitudinally every 3 months thereafter until death or last follow-up.

Results

12 patients were included, median age 70 years (range 61-83), 6 female. BTC subtypes: intrahepatic (9) and perihilar (1) cholangiocarcinoma, and gallbladder carcinoma (2). Median follow up was 20.5 months (range 6-33 months). Median tumor size was 5.2cm (range 2.1-8.3 cm), stage II-III disease 67%, R1 resection 33%. All patients received post-operative therapy: adjuvant capecitabine (9), chemoradiation (2), gemcitabine and cisplatin (1). Two patients received neoadjuvant gemcitabine and cisplatin. Pre-operatively, all 12 patients (100%) had detectable ctDNA, while only 4 pts (33%) had elevated CA 19-9. For post-operative MRD detection, 2/12 patients had a detectable ctDNA level, while none had an abnormal CA 19-9. Among 10 patients with undetectable ctDNA MRD postoperatively, 5 patients have remained ctDNA negative without evidence of recurrence, 4 of which are ctDNA negative for ≥18 months (range 20-33 months). During adjuvant therapy, 2 patients converted from ctDNA positive to negative, neither have recurred. During longitudinal follow up, 4/12 patients have confirmed recurrence: 1 patient was ctDNA MRD positive while the others converted from negative to positive during adjuvant therapy or surveillance. Rise in ctDNA preceded radiographic recurrence in all patients with recurrence.

Conclusions

Baseline ctDNA had higher detection rate compared to CA 19-9 prior to resection. Longitudinally negative ctDNA was associated with improved recurrence free survival. Assessing ctDNA levels may have potential utility in evaluating response in the absence of radiographically visible disease.

Clinical trial identification

NCT04561453.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Jurdi: Financial Interests, Institutional, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. C. Brdiges: Financial Interests, Institutional, Full or part-time Employment: Natera. All other authors have declared no conflicts of interest.