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Updated: Jun 4, 2026
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer
Published on: July 18, 2017
Circulating Tumor DNA Dynamics and Clinical Outcome in Metastatic Colorectal Cancer Patients Undergoing Front-Line
Michele Ghidini1, Jens Claus Hahne2,3, Chiara Senti4
1Division of Medical Oncology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Purpose:
We tested whether circulating tumor DNA (ctDNA) changes may be used to assess early response and clinical outcomes in patients with metastatic colorectal cancer (mCRC) undergoing first-line systemic anticancer therapy (SACT).
Experimental Design:
Eight hundred sixty-two plasma samples were collected 4-weekly from baseline (BL) until disease progression in patients with mCRC receiving first-line SACT. ctDNA was tested using tissue-agnostic next-generation sequencing panels. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the three variants with the highest allele frequency in BL ctDNA.
Results:
Eighty-three paired samples from 75 patients were available for analysis. Twelve pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients who cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared with nonnormalized patients [overall survival = 22.6 months (log-rank P = 0.01) and progression-free survival = 10.7 months (log-rank P = 0.036), respectively]. In addition, a higher response rate was observed in patients with ctDNA clearance (72.9%) compared with nonnormalized cases (38.2%). Longitudinal sequencing of at least four time points in patients with a progression-free survival of >10 months showed emerging variants in 47.8% of cases; in all these patients, the trajectory of these new "outlier" variants seemed in stark contrast with the clinical-radiological course of disease and the trend in other mutations.
Conclusions:
ctDNA clearance represents an early indicator of benefit from SACT in patients with mCRC; serial tracking of multiple variants is warranted to improve specificity and avoid misleading information due to the emergence of mutations of unknown clinical significance.
