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Updated: Jun 17, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid
C Valenza1, E F Saldanha2, Y Gong3
1Harvard Chan School of Public Health, Harvard University, Boston, USA; Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, USA.
Background:
In patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitor (ICI) therapy, identifying biomarkers to predict pathologic complete response (pCR) preoperatively could enhance treatment modulation. Circulating tumor DNA (ctDNA) clearance is a potential predictor of pCR, though its analytical and clinical validity has yet to be established. This systematic review and meta-analysis aims to assess the role of ctDNA clearance as a predictor of pCR in patients with solid tumors treated with neoadjuvant ICIs.
Materials And Methods:
A systematic search of PubMed, EMBASE and conference proceedings up to 5 August 2024 was carried out to identify phase Ib, II or III clinical trials investigating ctDNA clearance and pCR in patients with solid tumors and detectable ctDNA, undergoing neoadjuvant therapy with ICIs. Using a bivariate model, we estimated the pooled sensitivity and specificity of ctDNA clearance in predicting pCR, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio, with 95% confidence intervals (CIs).
Results:
Thirteen trials involving 380 patients with detectable ctDNA at baseline were included. ctDNA was assessed with a tumor-informed approach in 11 (85%) trials. Overall, 38% of patients achieved pCR and 73% had ctDNA clearance before/at the surgery. Pooled sensitivity was 0.98 (95% CI 0.86-1.00), specificity was 0.53 (95% CI 0.37-0.69), positive likelihood ratio was 2.09 (95% CI 1.48-2.93), negative likelihood ratio was 0.04 (95% CI 0.01-0.26), diagnostic odds ratio was 57.36 (95% CI 8.12-405.12). Significant heterogeneity was observed across studies (I2 ∼70% for all metrics), indicating considerable variability in the diagnostic performance.
Conclusion:
The lack of ctDNA clearance may identify patients unlikely to have a pCR. Instead, the confirmatory power of ctDNA clearance is limited by low specificity and high heterogeneity due to the variability of the assays, and warrants further study. Therefore, clinicians should not rely on the use of ctDNA clearance to inform treatment decisions in the neoadjuvant setting.
