Indicator of treatment success
A decrease in the level of circulating tumor DNA indicates the success of therapy
Bogdan Yanenko, PCR.news
A group of researchers from the USA confirmed the relationship between the level of tumor DNA (cDNA) circulating in the blood and the survival of patients with non-small cell lung cancer after immunotherapy with anti-PD-1 and anti-PD-L1 drugs. The work used data from five independent clinical trials involving 200 patients.
PD-1 and PD-L1 are so—called immune control points, molecules on the surface of cells that do not allow the immune system to attack them. They are expressed by some types of cancer. Blocking immune control points is considered one of the most promising methods of cancer therapy. Previously, several studies have shown that it is possible to track the response of patients to this type of immunotherapy and predict outcomes based on the content of cDNA in the blood. However, it was still unclear whether it was possible to generalize the data obtained, since different methods were used in these works. To standardize monitoring by data center collaboration Friends of Cancer Research has launched a ctMoniTR pilot project. The first step was the unification and harmonization of data on patients with non-small cell lung cancer receiving PD-1 and PD-L1 inhibitors.
The content of cDNA in the studies was evaluated using various NGS methods (targeted or genome-wide). In four out of five studies, the frequencies of mutant alleles carrying variants characteristic of the tumor were determined. In the fifth study, based on genome-wide sequencing, the tumor fraction was determined by changes in the number of copies and length of cDNA fragments.
Statistical analysis of the results showed that the frequency of mutant alleles at the beginning of the study was not associated with tumor progression and patient survival. But an increase in allelic frequency positively correlated with the risk of death. A decrease in the content of cDNA was associated with an improved tumor response to immunotherapy and a long-term clinical benefit for patients (progression-free survival was six months or more).
The results of the work show that changes in the cDNA can serve as the main or auxiliary tool for tracking the response to drugs and correcting treatment. The ctMoniTR project plans to expand research to cover more types and stages of cancer and types of therapies.
Article by Vega et al. Changes in Circulating Tumor DNA Reflect Clinical Benefit Across Multiple Studies of Patients With Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors is published in the journal JCO Precision Oncology.
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