P33: Personalized Circulating Tumor DNA and Survival in Patients with Resectable Pancreatic Cancer

Friday, March 24, 2023

1:16 PM – 1:21 PM

Location: SSO HUB Pan-Tumor Zone: CRS, HPB, Pan-Tumor & Upper GI

Poster Presenter(s)

Austin M. Eckhoff, MD

General Surgery Resident
Duke University
Durham, North Carolina, United States

Disclosure information not submitted.

Author(s)

Austin M. Eckhoff, MD

General Surgery Resident
Duke University
Durham, North Carolina, United States

Disclosure information not submitted.
EK

Elishama Kanu, MD

General Surgery Resident
Duke University Medical Center, United States

Disclosure information not submitted.
AF

Ashley Fletcher, BA

Research Manager
Duke University, United States

Disclosure information not submitted.
MB

Matthew Bao, BA

Research Assistant
Duke University, United States

Disclosure information not submitted.
DN

Daniel P. Nussbaum, MD

Assistant Professor of Surgery
Duke University Medical Center, United States

Disclosure information not submitted.
Dan Blazer, III, MD

Associate Professor of Surgery
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose
Michael E. Lidsky, MD

Assistant Professor of Surgery
Duke University
Durham, North Carolina, United States

Disclosure information not submitted.
Sabino Zani, Jr., MD

Associate Professor of Surgery
Duke University Medical Center
Durham, North Carolina, United States

Disclosure information not submitted.
KS

Kevin Shah, MD

Assistant Professor of Surgery
Duke University, United States

Disclosure information not submitted.
VA

Vasily Aushev, PhD

Senior Scientitist
Natera, United States

Disclosure information not submitted.
Sk

Shifra krinshpun, M.S.

Manager
Natera, United States

Disclosure information not submitted.
AJ

Adham Jurdi, MD

Medical Director
Natera, United States

Disclosure information not submitted.
ML

Minetta Liu, MD

Chief Medical Officer
Natera, United States

Disclosure information not submitted.
Peter Allen, MD

chief, surgical oncology
Duke University Medical Center
Durham, NC, United States

Disclosure information not submitted.
GH

Garth Herbert, MD

Assistant Professor of Surgery
Duke University, United States

Disclosure information not submitted.

Disclosure(s):

Dan Blazer, MD, III: No financial relationships to disclose

Introduction: Nearly all patients who undergo resection for pancreatic cancer (PDAC) will recur of their disease, many within 12 months of resection. Circulating tumor DNA (ctDNA) has been demonstrated to predict recurrence in several GI cancer sub-types. We tested a personalized, tumor-specific ctDNA assay as a possible approach for early detection and patient selection.

Methods: We assessed serial ctDNA measurements from 22 patients with newly diagnosed, resectable PDAC that underwent curative-intent resection. Patient-specific somatic mutations, identified by whole-exome sequencing of the primary tumor, were used to generate personalized ctDNA assays, which were then measured by ultra-deep sequencing of plasma DNA. Plasma samples (n=133) were procured at diagnosis, during neoadjuvant therapy if applicable, on the day of surgery, and every 2-3 months during adjuvant therapy/surveillance. Survival outcomes were estimated using the Kaplan-Meier method.

Results: Within our group of 22 patients, 6 (27%) patients received neoadjuvant therapy, and the overall median follow-up was 12 months. At the time of diagnosis, 7 patients had detectable ctDNA, and these patients demonstrated rapid recurrence compared to patients who were initially ctDNA negative (DFS 4.7 vs. 17.8 mo, p = 0.02) and experienced worse survival (OS 10.6 vs 22.6 mo, p = 0.13). Within the treatment period, 14 (63%) patients developed radiographic evidence of recurrence (median DFS 10 mo) and 7 of these had tested positive for ctDNA after resection. Positive ctDNA testing occurred at a median 7.5 months after resection and radiographic recurrence occurred at a median of 5.8 months (p=0.57). Three patients had persistently positive ctDNA and all three of these patients experienced rapid postoperative recurrence (mean 1.7 months). At the time of diagnosis, tumor size was associated with initial ctDNA positivity (p = 0.03), however serum CA 19-9 was not (p=0.42).

Conclusions: A positive ctDNA test at diagnosis was associated with significantly worse outcomes, and failure to convert to negative following resection was an ominous finding. Although several patients had disease recurrence despite being ctDNA negative, low plasma sample volumes and timing of ctDNA testing in relation to systemic chemotherapy may have affected the sensitivity of detecting recurrence.

Learning Objectives:

Identify patient and tumor characteristics associated with positive ctDNA at the time of PDAC diagnosis
Describe the role of ctDNA in predicting pancreatic cancer recurrence
Characterize disease free survival and overall survival in patients with positive ctDNA vs negative ctDNA at the time of PDAC diagnosis