Utilization of circulating tumor DNA (ctDNA) testing in biliary tract cancers.
Authors: Naleid Nikolas , Pawar Omkar , Patell Kanchi , Conces Madison , Lumish Melissa Amy , Selfridge J. Eva , Mohamed AMR , Bajor David L. , Chakrabarti Sakti , Mahipal Amit 
Published: January 2025

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Background:
There is limited data to guide surveillance in biliary tract cancers (BTCs) following resection. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) to detect early recurrence. Current data is limited on the use of ctDNA in biliary tract cancers in conjunction with surveillance imaging. In this study, we aim to elucidate the role of ctDNA monitoring in patients with biliary tract cancers who have undergone curative resection.
Methods:
We conducted a retrospective search at a tertiary care and several satellite settings to identify patients with BTCs who underwent curative surgery and subsequently had ctDNA monitoring. We collected demographic variables, disease characteristics, treatment regimens, and follow-up data. The primary endpoint of the analysis is recurrence-free survival (RFS), comparing patients with detectable ctDNA to those with negative ctDNA post-surgery. Kaplan-Meier analysis and Log-Rank tests were performed to evaluate RFS, and Cox proportional hazards(PH) models were employed for both univariate and multivariate analyses.
Results:
We identified 36 pts with a median age of 72 (34-87) yrs at diagnosis. In this study cohort, 22 (59%) were female, 32 (88%) were white, and 3 (8%) were African American. 12 (33%) pts were ctDNA positive at any point during surveillance, while the remainder were ctDNA negative. In the ctDNA-positive group, recurrences developed in 7 out of 12 (58%) pts. In the ctDNA negative group, only 2 out of 24 (8.3%) pts developed recurrences. The median time to recurrence following primary surgery was 10.7 months, while the time to ctDNA positivity following surgery was 7.8 months. The median time from ctDNA positivity to recurrence was 1.1 months. Pts with ctDNA positivity had a significantly lower 1-year RFS of 47.62% (95% CI: 7.5%-81%) compared to those with ctDNA negativity (85%, 95% CI: 60%-95%; p = 0.0008). Multivariate analysis demonstrated that ctDNA positivity at any point was associated with a significantly higher risk of recurrence (HR: 21.8, 95% CI: 2.3–203, p<0.0001).
Conclusions:
In pts with BTCs who underwent resection, ctDNA testing had independent prognostic value. Further prospective trials are needed to help define the role of ctDNA in this patient population.

Baseline demographics and clinical characteristics of patients who were ctDNA positive vs. negative.

Characteristics
Patients with Biliary Tract Cancers who were ctDNA positive
Patients with Biliary Tract Cancers who were ctDNA negative

N
12
24

Age in years, median (range)
72 (62 – 87)
72 (34 - 85)

Sex n (%)

Male
7 (58)
8 (33)

Female
5 (42)
16 (67)

Race n (%)

White
12 (100)
20 (83)

Black/African American
0 (0)
3 (13)

Asian
0 (0)
1 (4)

Primary Tumor Location n (%)

ICC
4 (33)
11 (46)

ECC
4 (33)
5 (21)

GBC
2 (17)
6 (25)

AC
2 (17)
2 (8)

Margin Status n (%)

Positive
2 (17)
3 (13)

Negative
10 (83)
21 (87)

Clinical Stage

I
0 (0)
1 (4)

II
2 (17)
12 (50)

III
8 (66)
10 (43)

IV
2 (17)
0 (0)

Unknown
0 (0)
1 (3)