Abstract 4689
Background
Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for early prediction of relapse across different tumor types. In patients with colorectal cancer (CRC), multiple studies have analyzed ctDNA to monitor tumor burden using fixed gene panels and droplet digital PCR. Here, we use a highly sensitive and specific, bespoke, whole exome-based NGS approach (Signatera™) for ctDNA monitoring.
Methods
A cohort of 33 patients with stage III CRC who underwent surgery and were treated with at least 4 months of adjuvant chemotherapy was analyzed. Mutational profiles derived from primary tumor tissue and germline DNA whole exome were used to design assays targeting tumor-specific somatic variants. The bespoke assays were used for ctDNA detection in plasma samples. Relapse-free survival (RFS) was calculated for patients stratified by ctDNA status.
Results
Plasma samples (n = 44; average volume=1.8mL) from patients (N = 33) were analysed for the presence of ctDNA. Of the five ctDNA-positive patients, clinical follow-up was available for three patients, all of whom relapsed (100%; 3/3); three of 27 ctDNA-negative patients (11%) also clinically relapsed. Molecular relapse through ctDNA analysis was detected up to 668 days ahead of radiological imaging with an average lead time of 305 days. The majority of relapses in ctDNA-positive patients (67%; 2/3) occurred within a year of follow-up, while no relapses were observed in ctDNA-negative patients during the one-year time frame. All plasma samples (n = 34) from 24 non-relapsing patients were ctDNA negative, corresponding to a specificity of 100%. The presence of ctDNA was associated with a markedly reduced RFS compared to ctDNA-negative patients (HR: 5.6; 95% CI: 0.6-52.1; p < 0.01).
Conclusions
The study results indicate that ctDNA status is associated with high relapse risk in patients with CRC and can serve as a predictor of patient outcome. Despite low plasma volumes (<5mL) and lack of longitudinal samples for analysis, ctDNA was detected in 50% of relapse cases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Natera, Inc. and NSABP Foundation.
Funding
Natera, Inc., Bayer, NSABP Foundation.
Disclosure
H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. T.J. George: Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Pharmacyclics. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A.S. Tin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Olson: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. D. Renner: Full / Part-time employment: Natera, Inc. E. Kalashnikova: Full / Part-time employment: Natera, Inc. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. R. Salari: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. B. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment, I am an employee of Natera and own stock/options to stock.: Natera, Inc. All other authors have declared no conflicts of interest.
Resources from the same session
5071 - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma
Presenter: Soohyeon Kwon
Session: Poster Display session 3
Resources:
Abstract
5306 - Real-world data of clinicopathologic characteristics of young oropharyngeal cancer patients.
Presenter: Maria Nieva
Session: Poster Display session 3
Resources:
Abstract
3407 - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma
Presenter: Shiqi Gong
Session: Poster Display session 3
Resources:
Abstract
3310 - Liquid biopsy for mutational profiling of locoregional recurrent and/or metastatic squamous cell carcinoma of the head and neck
Presenter: Rachel Galot
Session: Poster Display session 3
Resources:
Abstract
2362 - Blood-based testing of mutations in patients with Head and neck squamous cell carcinoma (HNSCC) using highly sensitive SafeSEQ technology
Presenter: Florentia Fostira
Session: Poster Display session 3
Resources:
Abstract
4533 - The head and neck Lung Immune Prognostic Index (HN-LIPI): a prognostic Score for Immune Checkpoint Inhibitors (ICI) in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) patients.
Presenter: Ruth Gabriela Herrera Gomez
Session: Poster Display session 3
Resources:
Abstract
5262 - Immune-related adverse events (irAEs) and outcome in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) patients (pts) treated by immune-checkpoints inhibitors (ICI)
Presenter: Neus Baste Rotllan
Session: Poster Display session 3
Resources:
Abstract
3725 - Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy
Presenter: Jack Bui
Session: Poster Display session 3
Resources:
Abstract
2533 - A nomogram based prognostic score to predict overall survival (OS) in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with immune checkpoint inhibitors (ICI).
Presenter: Luay Mousa
Session: Poster Display session 3
Resources:
Abstract
2929 - Changes of the Commensal Microbiome during Treatment are Associated with Clinical Response in the Nasopharyngeal Carcinoma Patients
Presenter: Tingting Huang
Session: Poster Display session 3
Resources:
Abstract