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Updated: Jun 30, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Early circulating tumor DNA dynamics predict fruquintinib efficacy in refractory metastatic colorectal cancer before
Hebin Hou1, Pingping Liu1, Xiaohuan Dong1
1Department of Gastroenterology, Tengzhou Central People's Hospital, Tengzhou, Shandong, China.
Background:
Treatment options for refractory metastatic colorectal cancer remain limited, and no biomarkers predict fruquintinib benefit before imaging. This study evaluated whether early dynamics of circulating tumor DNA predict efficacy and prognosis during fruquintinib treatment.
Methods:
This single-center prospective cohort study enrolled patients with refractory metastatic colorectal cancer receiving fruquintinib 5 mg daily. Blood was collected at baseline, day 14, and day 28 for circulating tumor DNA testing using high-depth panel sequencing with clonal hematopoiesis filtering. Based on the day-28 maximum variant allele frequency change from baseline, patients were categorized as clearance, decrease, stable, or increase. Progression-free and overall survival were evaluated using day-28 landmark analysis. Multivariable regression models adjusted for nine clinical covariates assessed disease control rate and progression-free survival. Model performance was evaluated using Harrell's C-index, time-dependent receiver operating characteristic (ROC), bootstrap validation, and sensitivity analyses.
Results:
Among 120 enrolled patients, 107 completed day-28 circulating tumor DNA testing. Day-28 dynamics showed clearance in 17.8% and a decrease in 43.9%. Compared with stable/increase, the clearance and decrease groups had higher disease control rates (adjusted odds ratios, 6.92 and 3.45; both P < 0.01) and lower progression risk (adjusted hazard ratios, 0.41 and 0.62; both P < 0.05). Adding circulating tumor DNA stratification improved model discrimination for progression-free survival (ΔC-index = 0.07) and overall survival (ΔC-index = 0.06). Areas under the curve for 3-month and 6-month progression-free survival were 0.73 and 0.68. Sensitivity analyses confirmed robustness across alternative thresholds (hazard ratio range, 0.49-0.61; all P < 0.01). Common adverse events included hypertension (46.7%), hand-foot skin reaction (40.8%), and fatigue (36.7%), with acceptable tolerability.
Conclusion:
Day-28 circulating tumor DNA dynamics predict efficacy and survival during fruquintinib treatment and enhance clinical model performance. However, the modest discriminative performance (C-index 0.69) indicates that prospective validation is required before clinical implementation. These findings support further investigation of ctDNA-guided risk stratification in refractory metastatic colorectal cancer.
