Early Relapse Detection and Monitoring Disease Status in Patients with Early-stage Pancreatic Adenocarcinoma using Circulating Tumor DNA

Author(s): Maen Abdelrahim, Abdullah Esmail, Jiaqiong Xu, Tiffany A Katz, Shruti Sharma, Ekaterina Kalashnikova, Meenakshi Malhotra, Perry Olshan, Paul R Billings, Alexey Aleshin

Pancreatic ductal adenocarcinoma (PDAC) has one of the most aggressive cancer histologies, with high recurrence (85%) and a 5-year survival rate of 9%. The circulating tumor DNA (ctDNA) is evolving field in setting of management for patients with advanced solid tumors. In this study, our aim was to investigate the potential contributions of ctDNA in early-stage pancreatic adenocarcinoma prognostication as early relapse detection and disease status monitoring and to evaluate the relationship with tumor markers carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9).

Methods: We enrolled 9 patients with pancreatic cancer from whom we collected paired tissue and plasma/serum samples. We analyzed the ctDNA of patients, with a median follow-up of 357 days, and monitored CEA and CA19-9, and radiological imaging. Personalized mutational profiles derived from tumor tissue via whole-exome sequencing were used to design patient-specific ctDNA assays for variant detection in plasma samples (Signatera test, Natera).

Results: We found that during the course of the follow-up, 44.4% (4/9) of patients relapsed. The presence of ctDNA was associated with reduced recurrence-free survival (p = 0.011). Importantly, ctDNA results were found to correlate and precede imaging results. In contrast, CA 19-9 and CEA, in certain cases showed discordance with imaging and were found to be elevated due to other benign conditions, such as gastritis.

Conclusion: This study demonstrates that presence of ctDNA after surgery in early-stage PDAC is associated with reduced recurrence-free survival. During monitoring, ctDNA was found to be a better prognostic marker compared to CA-19-9 and CEA and can be used to inform on disease status prior to imaging.