Australian researchers led an international study that evaluated five commercially available assays to diagnose and monitor cancer.
DNA-based tests represent a fast, cheap and non-invasive approach to diagnose and monitor cancer. However, until now there have been no clear evaluation of the efficacy reliability of these tests. Now, a new study, published in the journal Nature Biotechnology, is providing answers.
About the new study
An international team of researchers, led by Dr Ira Deveson, Head of the Genomic Technologies Group at the Garvan Institute of Medical Research, in New South Wales, has analysed five leading DNA cancer tests. Their findings show that all the DNA tests they evaluated could reliably detect circulating tumour DNA (ctDNA), as long as it was found at a level of 0.5% of the total DNA in blood, or higher.
ctDNA enters the bloodstream when cancer cells break down, releasing fragments of their DNA. DNA from cancer cells usually contains specific mutations, which can be detected by advanced DNA tests using next-generation sequencing. The use of such DNA tests can help identify and monitor cancer, and provide a less invasive option than traditional tissue biopsies.
However, while these ctDNA tests are already available, we lack a clear understanding of their accuracy.
In this new study, an international team of researchers from across Europe, Asia and the United States, evaluated the performance of current industry-leading ctDNA assays. The tests evaluated came from leading companies, like Roche Sequencing Solutions, Illumina, Integrated DNA Technologies and Burning Rock Dx and Thermo Fisher Scientific. For their analyses, researchers used synthetic experiments and mock-ctDNA reference samples.
What the study found
The results obtained support the use of these tests for the detection and monitoring of late-stage and metastatic tumours but may not be useful for early detection of cancer.
“The study shows that ctDNA sequencing tests generally work well and can accurately detect cancer mutations in the circulation. However, none of the participating assays could reliably detect very rare mutations, at around 1 in 1000 DNA molecules in the blood, which limits their suitability for certain applications such as early-stage cancer detection,” Dr Deveson said.
The results of this study provide valuable information about the use of ctDNA assays as cancer diagnostics, including best-practice guidelines and aspects that need further research and development.
Why this study matters
The study was an international effort, involving the Garvan Institute of Medical Research, the FDA National Center for Toxicological Research and the University of Arkansas for Medical Sciences. It also forms part of the Sequencing Quality Control Phase 2 project, an FDA-let initiative that aims to develop standard protocols and quality control metrics for the use of DNA-based testing in precision medicine. Their ultimate goal is for these tests to reach and help patients.
“By identifying the strengths and weaknesses of these techniques, the study clearly highlights priority areas for further development of ctDNA sequencing tests. We hope this will facilitate improvement of this exciting technology, leading to regulatory approvals and widespread adoption in Australia and globally,” Dr Deveson said.
“Our findings indicate that the participating ctDNA assays may be suitable for molecular stratification and profiling tumour evolution in advanced cancer patients. This should help clear a path for more advanced clinical trials of ctDNA assays,” says Associate Professor Donald Johann Jr., M.D., from the University of Arkansas for Medical Sciences College of Medicine departments of Biomedical Informatics and Internal Medicine, in a press release.
In Australia, no ctDNA test is currently approved for clinical use, as there have been no evaluation about the accuracy and reproducibility of these tests. With the results on this new study on the table, Dr Deveson hopes things will change.
“Our assay removes these question marks, showing which applications ctDNA sequencing is suitable for and which areas require further improvement. While a given ctDNA test must still go through the rigorous process to achieve regulatory approval in Australia, our study provides a framework to assist this process,” he said.