CtDNA for clinical decision support in pancreatic cancer.

Abstract

e16354 Background: Circulating tumor DNA (ctDNA) is increasingly used to inform therapeutic decisions and its applicability to pancreatic cancer is emerging. We explore the adoption of ctDNA profiling in patients presenting to our pancreatic cancer clinic to help guide localized and metastatic pancreatic cancer treatment. Methods: This was an IRB-approved retrospective cohort study of Signatera ctDNA profiling among patients with pancreatic cancer at Northwell Health between October 2021 and September 2023. Patients received ctDNA testing at various treatment timepoints and were categorized according to clinical context: neoadjuvant, adjuvant, surveillance, radiographic relapse, and metastatic. Average ctDNA level and conversion rates were calculated for each group. Results: There were 203 tests completed among 59 patients representing the following clinical contexts: 36% metastatic disease, 27% in the adjuvant setting, 23% during surveillance, 7% prior to surgery, and 6% after relapse. 43 patients had ctDNA tests that were drawn but were cancelled or could not be performed due to inadequate tissue samples, of which 8 had at least one completed test and were included in final analysis. Of all 27 metastatic patients, 8 patients had tests that were never completed. 46% of all tests were positive, which ranged from 0.3 to 8089 MTM/mL, and averaged 196 MTM/mL. 51% of all patients had ctDNA results that remained positive, 34% remained negative, and 15% changed over time from either positive to negative or vice versa. Median ctDNA level was 0.1 MTM/mL or less for patients who were tested prior to surgery or during adjuvant treatment or surveillance and the median ranged from 0.0-67.1 for patients with metastatic disease or relapse. All ctDNA tests sent after radiographic relapse also tested positive. Conclusions: ctDNA testing was most commonly performed in patients with localized disease on adjuvant chemotherapy, and in those with metastatic disease at time of diagnosis, who also had the highest rates of positive tests by stage at diagnosis. Given all patients tested during relapse had positive tests, ctDNA may be an early predictor of disease progression in patients with negative tests on surveillance. When tissue is limited, such as in metastatic patients who are less likely to undergo surgery, production of the ctDNA assay may be hindered. A prospective, larger scale, and more longitudinal study would add greater power and clinical context.