Related Experiment Video
Updated: Aug 2, 2026
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study
Background:
Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.
Patients And Methods:
This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria.
Results:
ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004).
Conclusion:
This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.
Insights
Monitoring circulating tumor DNA (ctDNA) levels shows promise for assessing treatment response in patients receiving anti-PD-1 immune checkpoint blockers. Undetectable ctDNA levels at 8 weeks correlate with lasting responses and improved survival outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Immune checkpoint blockers (ICBs) like anti-PD-1 antibodies show clinical efficacy but pose challenges for radiological assessment due to tumor immune infiltration.
- Circulating tumor DNA (ctDNA) monitoring offers a potential non-invasive method for evaluating ICB treatment efficacy, yet data are limited.
Purpose of the Study:
- To investigate the utility of quantitative ctDNA monitoring for assessing treatment response in patients receiving anti-PD-1 therapy.
- To correlate ctDNA level changes with radiological tumor response and patient survival outcomes.
Main Methods:
- A prospective pilot study involving patients with non-small cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated with nivolumab or pembrolizumab.
- ctDNA levels were measured at baseline and 8 weeks using various molecular techniques (pyrophosphorolysis-activated polymerization, droplet digital PCR, next-generation sequencing).
- Treatment efficacy was evaluated using immune-related response criteria for radiological assessment.
Main Results:
- ctDNA was detected at baseline in 10 of 15 patients.
- A significant correlation (r=0.86, P=0.002) was found between changes in ctDNA levels and tumor size at 8 weeks.
- Patients with undetectable ctDNA at 8 weeks showed marked, lasting responses.
- ctDNA detection at 8 weeks was a significant prognostic factor for progression-free survival (HR=10.2) and overall survival (HR=15).
Conclusions:
- Quantitative ctDNA monitoring is a valuable tool for assessing tumor response in patients treated with anti-PD-1 drugs.
- ctDNA dynamics provide early insights into treatment efficacy and patient prognosis, complementing traditional radiological assessments.
More Related Videos
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
06:07Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
