44: Utility of circulating tumor DNA (ctDNA) for detection of minimal residual disease (MRD) after curative-intent therapy in localized pancreatic cancer (PDAC)

Thursday, March 21, 2024

2:22pm – 2:32pm ET

Location: C101

Abstract Presenter(s)

Ujwal R. Yanala, MD

Surgical Oncology Fellow
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States

Submitter(s)

Ujwal R. Yanala, MD

Surgical Oncology Fellow
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States

Author(s)

Ujwal R. Yanala, MD

Surgical Oncology Fellow
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
MM

Mary Martos, MD

Resident
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
ED

Erin M. Dickey, MD, MBS

Post Doctoral Fellow
Department of Surgery, University of Miami Miller School of Medicine, United States
AC

Andres Corona, MD

Resident
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
NE

Nkiruka Ezenwajiaku, MD

Assistant Professor
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
JP

Joseph Pizzolato, MD

Associate Professor
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
GT

Gretel Terrero, MD

Associate Professor
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
CH

Caitlin A. Hester, MD

Assistant Professor of Clinical Surgery
Division of Surgical Oncology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Cente, United States
NM

Nipun B. Merchant, MD

Surgical Oncologist
Department of Surgery, University of Miami, United States
PH

Peter Hosein, MD

Associate Professor
University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center., United States
Jashodeep Datta, MD (he/him/his)

Assistant Professor of Surgery
Department of Surgery, University of Miami Sylvester Comprehensive Cancer Center
Pinecrest, Florida, United States

Disclosure(s):

Ujwal R. Yanala, MD: No financial relationships to disclose

Jashodeep Datta, MD: Cantargia AB, Inc: Research Grant (Ongoing)

Introduction: Patients with localized PDAC have a high recurrence rate even after curative-intent surgery and chemotherapy. Detection of MRD in this setting can inform prognosis and may be actionable. While CA19-9 may detect recurrence, it lacks specificity and ~20% of patients (pts) are non-producers. ctDNA has been shown to be useful for MRD detection in other cancers but its utility in PDAC is not well established.

Methods: PDAC pts who had a ctDNA assay (Natera) after completion of curative-intent therapy in the MRD setting were included. Recurrence and survival data were correlated with end-of-treatment (EOT) ctDNA results. Published studies (n=3) examining ctDNA for MRD detection in PDAC using the same testing platform were identified. Data were pooled to determine EOT ctDNA positivity rate, positive and negative predictive values (PPV, NPV), and lead time from a positive (+ve) ctDNA to recurrence.

Results: Of 33 pts with EOT ctDNA data at our center, ctDNA was +ve in 10 (30.3%). At a median follow-up time of 14.3 months, median recurrence free survival (RFS) for +ve vs -ve ctDNA was 3.6 vs 25.1 months (HR=15.8 [4.7-53.4], p< 0.001). Correlation of +ve ctDNA with recurrence showed a sensitivity of 52% (10/19), specificity of 100% (14/14), PPV of 100% (10/10) and NPV of 61% (14/23). Our data were then combined with 138 pts reported in 3 prior studies, totaling 171 pts. Median follow-up ranged from 11.9-14.3 months and the overall EOT ctDNA +ve rate was 39% in the pooled cohort. The pooled sensitivity was 67% (49/73), specificity 83% (81/98), PPV 74% (49/66) and NPV 77% (81/105). In each study and the pooled analysis, an EOT +ve ctDNA was associated with significantly shorter RFS (HR=8.1-120.5). Among 10 pts at our institution with recurrence, +ve ctDNA test was detected after the recurrence 90% of the time, with a median lag-time of 4.70 months (range 2.2-16.67 months). In the pooled cohort, among 73 pts with recurrences, the ctDNA was +ve before, at the time of, or after the recurrence event in 23 (32%), 9 (12%) and 17 (23%) pts respectively; ctDNA was -ve despite recurrence in the remaining 24 (33%) pts.

Conclusions: Tumor-informed positive ctDNA test at EOT shows high specificity and PPV for recurrence and is associated with significantly worse RFS in the MRD setting; however, sensitivity of the test remains low. When positive, ctDNA assessment provides an opportunity for novel therapies in the adjuvant setting to improve outcomes for localized PDAC.

Learning Objectives:

Upon completion, participants will be able to understand the role of ctDNA in Pancreatic cancer
Upon completion, participants will be able to use ctDNA testing for surveillance
Upon completion, participants will be able to describe the ctDNA findings and their association with recurrence-free survival.