4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)

Background

Genomic instability as characteristic for malignant transformation can be identified by quantitative sequencing. Cell-free tumor DNA (cfDNA) is a minimal invasive biomarker that can be used for tumor and therapeutic monitoring. This study evaluates quantitative cfDNA in patients (pts) with pancreatic cancer (PDAC) as an early therapeutic outcome marker.

Methods

In this prospective study plasma samples of 59 PDAC pts were collected in two centers throughout treatment with either FOLFIRINOX (n = 35) or Gemcitabine/nab-paclitaxel (n = 24). Additionally in 17 pts with FOLFIRINOX samples were collected during and 8 hours after treatment initiation. CNI scoring assays were used to quantify cfDNA. The results were correlated to CT/MRT imaging (RECIST 1.1) after 8-12 weeks, or monthly CA 19-9 and CEA values.

Results

At base-line in 55 out of 59 samples cfDNA could be detected. The CNI scores in metastasized PDAC were significant higher in comparison to locally advanced tumors (p = 0.009), however no differences occurred between the centers, therapy regime or outcome. Results to sensitivity, specificity, PPV and accuracy of CNI scores after 3 month of treatment are given in the table. Especially in sensitivity and accuracy CNI score show an advantage above classical tumor marker. Moreover, a dramatic cytolytic burst with subsequent significant increased CNI score 8 hours after treatment initiation with FOLFIRINOX was observed in 3/4 pts with PR, 1/4 pts with SD, compared to 0/9 pts with PD. This makes the CNI sore a very early predictor of treatment failure sensitive during first administration of chemotherapy.Table:

717P CNI and CA19-9 for prediction of therapy outcome

Conclusions

Determination of cfDNA in the serum predicts treatment outcome more precise and earlier compared to classical tumor marker such as imaging or CA19-9 in PDAC patients. Prediction of non responsivness to therapy might even be possible after the first administration of FOLFIRINOX.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.