Abstract 4557
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
FOLFIRINOX CNI | FOLFIRINOX CA19-9 | Gem/nab CNI | Gem/nab CA19-9 | |
---|---|---|---|---|
Sens PD (%) | 73 | 36 | 50 | 18 |
Spec PD (%) | 88 | 88 | 93 | 62 |
PPV (%) | 89 | 100 | 86 | 40 |
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.
Resources from the same session
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract
2786 - Development of a living organoid biobank derived from colorectal cancer patients: towards personalized medicine
Presenter: Federica Papaccio
Session: Poster Display session 2
Resources:
Abstract
3351 - Microsatellite Instability Detection in Colorectal Cancer: 44-Center Comparison between the Idylla MSI Assay and Routine Molecular and Immunohistochemistry Tests on Formalin-Fixed Paraffin-Embedded Tissue
Presenter: Xavier Matias-guiu
Session: Poster Display session 2
Resources:
Abstract
4901 - Expression profile of EPHB3 and its prognostic significance in colorectal cancer progression (Running head: Prognostic value of EPHB3 in colorectal cancers)
Presenter: Bogun Jang
Session: Poster Display session 2
Resources:
Abstract
5030 - A pan-ErbB family inhibitor, AF8c, promotes apoptosis by DR5/Nrf2 activation via ROS in colorectal cancer cells
Presenter: Soyeon Jeong
Session: Poster Display session 2
Resources:
Abstract
5053 - Frequent BRAF, GNAS and SMAD4 mutations identified in Colorectal Mucinous Carcinomas
Presenter: Sun Mi Lee
Session: Poster Display session 2
Resources:
Abstract
5220 - Impact of CCL4 knockout using CRISPR Cas-9 technology on colorectal tumor progression
Presenter: Roba Barakat
Session: Poster Display session 2
Resources:
Abstract
5330 - Independent clinical validation of a gene expression profile to predict benefit of 5-FU in metastatic colorectal cancer
Presenter: Ida Buhl
Session: Poster Display session 2
Resources:
Abstract
5515 - WRN mutated Colorectal Cancer (CRC) is characterized by a distinct molecular and immunological profile
Presenter: Andreas Seeber
Session: Poster Display session 2
Resources:
Abstract
5716 - Mutation analysis of B2M gene in colorectal cancer patients with microsatellite instability
Presenter: Ivana Kašubová
Session: Poster Display session 2
Resources:
Abstract