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Updated: Jul 9, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal
Daniele Lavacchi1, Stefania Gelmini2, Adele Calabri2
1Clinical Oncology Unit, Careggi University Hospital, Florence, Italy.
Abstract:
The detection of RAS mutations and co-mutations in liquid biopsy offers a novel paradigm for the dynamic management of metastatic colorectal cancer (mCRC) patients. Expanding the results of the prospective OMITERC (OMIcs application from solid to liquid biopsy for a personalized ThERapy of Cancer) project, we collected blood samples at specific time points from patients who received a first-line chemotherapy (CT) for KRAS-mutated mCRC. CTC quantification was performed by CellSearch® system. Libraries from cfDNA were prepared using the Oncomine™ Colon cfDNA Assay to detect tumour-derived DNA in cfDNA. The analysis involved >240 hotspots in 14 genes. Twenty patients with KRAS-mutated mCRC treated at the Medical Oncology Unit of Careggi University Hospital were prospectively enrolled. Nine patients had available data for longitudinal monitoring of cfDNA. After 6 weeks of first-line CT an increase of KRAS-mutated clone was reported in the only patient who did not obtain disease control, while all patients with decrease of KRAS clones obtained disease control. Overall, in patients with a short (<9 months) progression-free survival (PFS) we registered, at 6 weeks, an increase in cfDNA levels and in KRAS mutations or other co-mutations, i.e. PIK3CA, FBXW7, GNAS, and TP53. In selected cases, co-mutations were able to better anticipate radiological progressive disease (PD) than the increase of KRAS-mutated clones. In conclusion, our study confirms plasma ctDNA as a crucial tool for anticipating PD at an early time point and highlights the value of a comprehensive assessment of clonal dynamics to improve the management of patients with mCRC.
Insights
Liquid biopsy detecting RAS mutations in metastatic colorectal cancer (mCRC) can dynamically manage treatment. Early detection of clonal changes in cfDNA can predict disease progression, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Metastatic colorectal cancer (mCRC) management benefits from dynamic monitoring.
- RAS mutations are key drivers in mCRC.
- Liquid biopsy offers a non-invasive approach for tracking cancer evolution.
Purpose of the Study:
- To evaluate the utility of liquid biopsy in monitoring treatment response and predicting progression in KRAS-mutated mCRC patients.
- To assess the role of cfDNA analysis for RAS mutations and co-mutations in predicting progression-free survival.
Main Methods:
- Prospective study of 20 KRAS-mutated mCRC patients receiving first-line chemotherapy.
- Longitudinal monitoring of circulating tumor DNA (ctDNA) using cfDNA analysis (>240 hotspots in 14 genes).
- Correlation of ctDNA dynamics with treatment response and radiological progression.
Main Results:
- An increase in KRAS-mutated clones in cfDNA at 6 weeks correlated with lack of disease control.
- Patients achieving disease control showed a decrease in KRAS clones.
- Patients with short progression-free survival exhibited increased cfDNA levels and mutations (KRAS, PIK3CA, FBXW7, GNAS, TP53) at 6 weeks.
- Co-mutations sometimes predicted progressive disease earlier than KRAS clone increase.
Conclusions:
- Plasma ctDNA is a valuable tool for early anticipation of progressive disease in mCRC.
- Comprehensive assessment of clonal dynamics in ctDNA improves mCRC patient management.
- Liquid biopsy enables dynamic, personalized therapy adjustments for mCRC.
