Personalized tumor-informed circulating tumor DNA monitoring for early detection of recurrence in postoperative pancreatic cancer

TL;DR

This study shows that tracking tumor DNA in the blood after surgery can help detect early signs of pancreatic cancer returning, especially after chemotherapy.

Contribution

The study introduces a personalized ctDNA monitoring approach for postoperative pancreatic cancer recurrence detection.

Findings

Personalized ctDNA monitoring detected recurrence up to 15.61 months before radiological diagnosis.

ctDNA detection after chemotherapy completion had a high negative predictive value of 82.4%.

ctDNA presence was strongly linked to shorter survival times.

Abstract

Up to 80% of patients with resected pancreatic cancer experience recurrence within 2 years. We evaluated the feasibility and accuracy of a personalized, tumor-informed circulating tumor DNA (ctDNA) test for the early detection of recurrence risk during long-term postoperative surveillance.

We recruited 43 patients with pancreatic cancer who underwent curative surgical resections. A personalized panel was developed to detect ctDNA in plasma based on whole-exome mutation information derived from tumor tissues. A total of 139 plasma samples were analyzed to assess recurrence risk and the efficacy of adjuvant therapy.

A personalized ctDNA monitoring panel was successfully customized in 35 of 43 cases. Sixteen patients relapsed within a median of 15.7 months (range: 5.4–30.0 months) postsurgery. For the 11 patients with positive ctDNA, the median lead time from initial ctDNA positivity to radiological relapse was 4.59 months (range: 0.88–15.61). After completion of adjuvant chemotherapy (ACT), 94.3% (33/35) of patients contributed 52.5% (73/139) of the ctDNA testing samples. These samples exhibited an elevated rate of ctDNA detection (48.5%, 16/33) compared to samples obtained prior to and during the commencement of ACT, with a negative predictive value of 82.4% (14/17) and a positive predictive value of 75.0% (12/16). The presence of ctDNA was significantly correlated with shorter disease-free survival and overall survival.

Long-term dynamic ctDNA monitoring after pancreatic cancer resection, particularly following the completion of ACT, is predictive of recurrence risk. The proactive implementation of ctDNA monitoring after ACT in patients with resectable pancreatic cancer has important implications for clinical practice.

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