Abstract 2465
Background
Circulating DNA (cfDNA) has emerged as a potential biomarker in cancer, and is the subject of extensive studies in translational and clinical research. Our group has been interested in its implication and clinical significance in the field of oncology for many years, and is now focused on evaluating its potential for early cancer detection.
Methods
We recently developed a screening test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences.
Results
When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. An extensive evaluation of this test was carried out in plasma samples of 289 healthy subjects and 987 cancer patients (CRC, breast, liver, pancreatic, ovarian) of all stages. Preliminary results revealed a high potential with an AUC of 0.81 (0.78-0.84, 95% CI), a 70% sensitivity (Se) and 77% specificity (Sp). In breast cancer (N = 169), an AUC of 0.82 (0.78-0.86, 95% CI) with 72% Se and 80% Sp were observed. In all stages CRC patients (N = 795), the results showed an AUC of 0.80 (0.78-0.84, 95%, CI), 75% Se and 70% Sp; for CRC stages 0/I/II (N = 426), an AUC of 0.79 (0.75-0.82, 95% CI), 70% Se and 72% Sp; and for CRC stage IV (N = 186), a 0.86 AUC (0.82-0.89, 95% CI) with 75% Se and 80% Sp. When combining the MNR to a total cfDNA concentration threshold value (AUC = 0.81 (0.79-0.83, 95% CI), 72% Se and 76% Sp for all stage cancers (N = 987)), in a test cohort of 173 stages 0/I/II CRC patients and 132 healthy individuals, we increased the sensitivity and specificity to 74% and 95% respectively. Furthermore we recently discovered that cfDNA fragmentation, as determined by Whole Genome Sequencing using either double or single strand library, is also a parameter enabling discrimination between healthy and cancer individuals.
Conclusions
The implementation of a multi-parametric test combining total cfDNA quantification, MNR and fragmentation biomarkers, with help of a decision tree in machine learning, is currently on-going. Our data suggest that our strategy in targeting cfDNA structural features might be powerful for early cancer detection, and appears as an alternative or a synergistic combination to the detection of mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Alain R. Thierry - INSERM (Institut national de la santé et de la recherche médicale).
Funding
MSDAvenir - Mitest / Alain R. Thierry is supported by INSERM (Institut national de la santé et de la recherche médicale).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract