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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
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Circulating Tumor DNA Dynamics in Patients with Liver-Limited Metastatic Colorectal Cancer Resected after First-Line
Roberto Moretto1, Vittorio Studiale1,2, Seung Won Hyun3
1Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Summary
Pre-surgery circulating tumor DNA (ctDNA) changes can predict relapse-free survival in metastatic colorectal cancer (mCRC) patients. A significant ctDNA reduction before surgery indicates better outcomes, aiding personalized treatment decisions.
Area of Science:
- Oncology
- Molecular Diagnostics
- Colorectal Cancer Research
Background:
- Resection of liver metastases improves survival in metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD).
- Relapse after surgery is common, and while post-resection circulating tumor DNA (ctDNA) is prognostic, pre-surgery ctDNA data after chemotherapy is limited.
- Accurate prognostic biomarkers are crucial for optimizing treatment strategies in mCRC.
Purpose of the Study:
- To evaluate the prognostic effect of pre-surgery ctDNA levels and dynamics after upfront chemotherapy in patients with initially unresectable mCRC and LLD undergoing resection.
- To assess the utility of a tumor-naive minimal residual disease (MRD) assay for ctDNA detection in this setting.
- To determine if ctDNA dynamics can stratify recurrence risk post-surgery.
Main Methods:
- 116 patients with initially unresectable mCRC and LLD who received upfront chemotherapy followed by resection were included.
- A tumor-naive ctDNA-based MRD assay was used for sequencing at baseline (pre-chemotherapy), pre-surgery, and post-surgery.
- Relapse-free survival (RFS) and recurrence were analyzed in relation to ctDNA status and dynamics.
Main Results:
- Pre-surgery ctDNA status alone was not significantly associated with RFS.
- A ≥50% reduction in variant allele frequency (VAF) from baseline to pre-surgery independently predicted improved RFS (21.0 vs. 9.8 months).
- Post-surgery ctDNA positivity strongly predicted recurrence (HR: 6.66), and ctDNA dynamics from pre- to post-surgery further stratified risk.
Conclusions:
- A tumor-naive MRD assay enhances ctDNA detection accuracy after chemotherapy, identifying significant ctDNA drops.
- Pre-surgery ctDNA dynamics are prognostic for relapse-free survival in mCRC patients undergoing resection.
- These findings may help stratify patient prognosis before surgery and inform personalized treatment decisions.
