Role of ctDNA to Predict Risk for Recurrence Following Potentially Curative Resection of Biliary Tract and Pancreatic Malignancies

Results of a pilot study demonstrate the feasibility of ctDNA testing and the prognostic value of ctDNA following potentially curative resection in patients with pancreatic/biliary tract malignancies.

This pilot study was conducted to assess the potential role of ctDNA in identifying residual disease following surgical resection in patients with pancreatico-biliary malignancies—particularly the impact of the presence of ctDNA postcurative resection on patient outcomes (ie, relapse-free survival [RFS] and relapse rate). The results of the analysis were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The retrospective study included patients diagnosed with pancreatico-biliary malignancies who underwent molecular profiling using ctDNA following potentially curative resection. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF), were identified. The primary objective was to determine the prevalence of ctDNA identification and its correlation with recurrence (RFS and relapse rate). The date of data cutoff was June 25, 2020.

The study enrolled a total of 11 patients with pancreatico-biliary malignancies with evaluable ctDNA postresection. Of the 8 biliary tract cancers, 4 had extrahepatic cholangiocarcinoma (CCA), 2 had ampulla, 1 had intrahepatic CCA, and 1 had gallbladder cancer. The median age of all 11 patients was 71.59 years. The majority of the participants were female (54.6%). Most patients were staged pT2 (45.45%), pN0 (54.55%), and R0 (63.64%).

At a median follow-up of 11.15 months, the median RFS was 11.43 months; the median overall survival was not reached. Of the 11 samples that had ctDNA data, the presence of ctDNA was detected in 3 (27.27%) samples. Genetic alterations identified in these 3 samples included fusion, TP53 mutation, CHEK2 mutation, and IDH2 mutation. The mean maximum MAF was 1.47 (2 in biliary and 0.43 in pancreas). Overall, 72.73% of the samples had variants of unknown significance.

A trend toward increased relapse risk was observed in patients with ctDNA that was present postresection compared with those with no ctDNA, which did not reach statistical significance (median RFS, 11.44 months vs 10.87 months, respectively; hazard ratio, 2.64). The estimated relapse rate was 37.5% in patients with no ctDNA compared with 66.67% in patients who had ctDNA present. The median RFS was longer in patients with no ctDNA (11.44 vs 10.87 months in those with ctDNA present).

These results demonstrate the feasibility of ctDNA testing following potentially curative resection and the prognostic value of ctDNA in pancreatic/biliary malignancies. Additional studies are warranted to confirm these results.

Source: Lamarca A, McNamara MG, Hubner R, Valle JW. Role of ctDNA to predict risk of recurrence following potentially curative resection of biliary tract and pancreatic malignancies. J Clin Oncol. 2021;39(suppl_3):336-336.