Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Circulating tumor DNA (ctDNA) is found in the bloodstream and refers to DNA that comes from cancerous cells and tumors. Most DNA is inside a cell’s nucleus. As a tumor grows, cells die and are replaced by new ones. The dead cells get broken down and their contents, including DNA, are released into the bloodstream. ctDNA are small pieces of DNA, usually comprising fewer than 200 building blocks (nucleotides) in length.

The quantity of ctDNA varies among individuals and depends on the type of tumor, its location, and for cancerous tumors, the cancer stage.

Detection of ctDNA can be helpful in the following cases:

Detecting and diagnosing a tumor. Because tumor DNA has acquired multiple genetic mutations, leading to tumor development, ctDNA is not an exact match to the individual’s DNA. Finding DNA with genetic differences aids in tumor detection. Diagnosing the type of tumor using ctDNA can reduce the need for getting a sample of the tumor tissue (tumor biopsy), which can be challenging when a tumor is difficult to access, such as a tumor in the brain or lung.

Guiding tumor-specific treatment. Analyzing the genome of tumor cells using ctDNA can help doctors determine which treatment will be most effective. Currently, however, approval from the U.S. Food and Drug Administration for ctDNA testing to personalize cancer treatment is limited.

Monitoring treatment. A decrease in the quantity of ctDNA suggests the tumor is shrinking and treatment is successful.

Monitoring periods with no symptoms (remission of cancer). A lack of ctDNA in the bloodstream indicates that the cancer has not returned.

Scientists have discovered that dying tumor cells release small pieces of their DNA into the bloodstream. These pieces are called cell-free circulating tumor DNA (ctDNA)

https://ghr.nlm.nih.gov/primer/testing/ ... ngtumordna

Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer.



Abstract
Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of circulating tumor DNA (ctDNA) on the efficacy of nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of nivolumab and at the first tumor evaluation with nivolumab. ctDNA was analyzed by Next-Generation Sequencing (NGS), and the predominant somatic mutation was followed for each patient and correlated with tumor response, clinical benefit (administration of nivolumab for more than 6 months), and progression-free survival (PFS). Of 23 patients, 15 had evaluable NGS results at both times of analysis. ctDNA concentration at the first tumor evaluation and ctDNA change correlated with tumor response, clinical benefit and PFS. ROC curve analyses showed good diagnostic performances for tumor response and clinical benefit, both for ctDNA concentration at the first tumor evaluation (tumor response: positive predictive value (PPV) at 100.0% and negative predictive value (NPV) at 71.0%; clinical benefit: PPV at 83.3% and NPV 77.8%) and the ctDNA change (tumor response: PPV 100.0% and NPV 62.5%; clinical benefit: PPV 100.0% and NPV 80.0%). Patients without ctDNA concentration increase >9% at 2 months had a long-term benefit of nivolumab. In conclusion, NGS analysis of ctDNA allows the early detection of tumor response and long-term clinical benefit with nivolumab in NSCLC.

https://europepmc.org/article/PMC/5927532

Association Between Circulating Tumor DNA and Pseudoprogression in Patients With Metastatic Melanoma Treated With Anti–Programmed Cell Death 1 Antibodies


Question What is the predictive value of circulating tumor DNA in differentiating pseudoprogression from true progression in patients with metastatic melanoma treated with anti–programmed cell death 1 antibodies?

“Findings In this cohort study of 125 patients with metastatic melanoma who were treated with anti–programmed cell death 1 antibodies, the number of circulating tumor DNA copies was reduced by greater than 10-fold within 12 weeks of treatment and accurately identified patients with pseudoprogression. These profile patterns of circulating tumor DNA were significantly associated with overall survival.

Meaning Reduction in the number of circulating tumor DNA copies within 12 weeks of anti–programmed cell death 1 inhibitor treatment represents a liquid molecular biomarker profile for prognosis.“


https://jamanetwork.com/journals/jamaon ... ct/2671602