Clinical utility of circulating tumor DNA (ctDNA) in resectable pancreatic ductal adenocarcinoma (PDAC)

Background

There is considerable interest in investigating ctDNA as a non-invasive biomarker, with potential utility in screening, detecting minimal residual disease after curative resection and monitoring treatment response or resistance. Here we perform sequential ctDNA quantification in patients (pts) with resectable PDAC using a novel and highly sensitive multiplex technology to explore the clinical utility of ctDNA as a diagnostic and prognostic biomarker.

Methods

Banked plasma and tumor samples from 32 pts with resected PDAC were retrieved. Plasma samples were collected 0-28 days before, and 28-70 days after surgery. DNA was extracted using standard protocols and analyzed using the OnTarget system, which enriches for DNA molecules containing hot spot mutations prior to sequencing. A 96-plex panel that includes the most prevalent mutations in KRAS, PIK3CA and TP53 was used.

Results

29 pts (91%) had at least 1 mutation detected by OnTarget in the tumor sample, most frequently in KRAS codon 12 (n = 26). 25 of 29 pts with a panel-detected tumor mutation had a pre-operative blood sample available, where a concordant mutation was detected in 8 pts (sensitivity 32%). There was no correlation between pre-operative ctDNA and tumor pathologic features. At median follow-up of 16.5 months, there was no difference in recurrence-free survival (RFS) between pts with and without detectable pre-operative ctDNA (p = 0.595). Of the 22 available post-operative blood samples, a concordant mutation was detected for 5 pts. RFS was significantly shorter in pts with concordant ctDNA detected after surgery (median 2.1 vs 11.6 months, p 

Conclusions

Pre-operative ctDNA has low sensitivity, suggesting limited utility in PDAC screening, and does not appear to be prognostic. RFS was significantly shorter in pts with detectable tumor-specific ctDNA post-operatively; this analysis is limited by small numbers and short follow-up. The significance of discordant plasma and tumor mutations is unknown.

Clinical trial identification

Legal entity responsible for the study

Pancreas Centre BC

Funding

Pancreas Centre BC

Disclosure

D.J. Renouf: Honorarium from Celgene Canada. All other authors have declared no conflicts of interest.