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
5472 - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC)
Presenter: Camilla Qvortrup
Session: Poster Display session 2
Resources:
Abstract
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract