Abstract 5779
Background
Drug resistance is an important clinical problem affecting the prognosis of colorectal cancer patients with initially unresectable liver metastases. The role of 5-hydroxymethylcytosine (5-hmC) in this process is still unknown.
Methods
A single-center study was conducted to enroll colorectal cancer patients with initially unresectable liver metastases at Zhongshan Hospital, Shanghai. The 5-hmC levels of each gene locus in circulating-free DNA (cfDNA) were detected using a highly sensitive sequencing method before the patient received any conversion therapy. Eight weeks after conversion therapy, patients with disease progression according to RECIST 1.1 were defined as drug-resistant group, while patients with complete response, partial response and stable disease were defined as the drug-effective group. By using the gene loci with the most significant difference of 5-hmC level, a predictive model (Logistic regression) was established based on machine-learning method. Then, we validated the model.
Results
From June 2018 to January 2019, 35 patients were enrolled, including 20 patients in drug-effective group and 15 in drug-resistant group. The predictive model was established using the first 100 significantly different gene loci and 10 loci were included in the model. The internal validation results suggested that the sensitivity (predictive accuracy for drug-resistant patients) and specificity (predictive accuracy for drug-effective patients) were 86.7% and 95.0%, respectively, and the area under the ROC curve is 0.990.
Conclusions
Our study screened the gene loci with different 5-hmC level between drug-effective and drug-resistant colorectal cancer patients with initial unresectable liver metastases. Then we established a predictive model for the efficacy of conversion therapy, although this model is still being improved and validated by enrolling more subjects.
Clinical trial identification
NCT03679039 09/18/2018.
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
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract
1694 - Pembrolizumab (pembro) Plus mFOLFOX or FOLFIRI in Patients With Metastatic Colorectal Cancer (mCRC): KEYNOTE-651 Cohorts B and D
Presenter: Richard Kim
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract