An global group today reports the findings of an independent evaluation of 5 commercially-available assays for growth DNA sequencing – a quick, inexpensive and less intrusive technique to detect and keep an eye on cancer.
The scientists exposed that all assays might dependably find so-called flowing growth DNA (ctDNA) when it comprised 0.5% of the overall DNA in blood, a level of level of sensitivity that permits detection, hereditary analysis and tracking of late-stage and metastatic growths.
Published in the journal Nature Biotechnology, the research study is a significant turning point for making use of ctDNA assays as cancer diagnostics, describing best-practice standards and discovering crucial locations of future advancement.
The research study was led by the Garvan Institute of Medical Research, the FDA National Center for Toxicological Research and the University of Arkansas for Medical Sciences. It forms part of the FDA-led Sequencing Quality Control Phase 2 job, which intends to establish basic procedures and quality assurance metrics for making use of next-generation sequencing in accuracy medication, to make it a truth for clients.
“In order for ctDNA assays to be of benefit to patients in the clinic, they need to accurately and consistently detect cancer mutations across different labs and samples. Our study is the most comprehensive evaluation of analytical performance among ctDNA assays to date and represents a significant step forward in the field,” states very first author Dr. Ira Deveson from the Garvan Institute.
Next-generation sequencing to keep an eye on cancer DNA
When cancer cells establish, they collect anomalies in their DNA, pieces of which go into the blood stream when cancer cells break down. Thanks to assays using next-generation sequencing, these ctDNA pieces can now be spotted in a client’s blood samples, which might be utilized to determine and keep an eye on cancer as an option to more intrusive tissue biopsies.
However, while ctDNA assays are currently being embraced in accuracy oncology medical trials, scientists and clinicians still do not have a comprehensive understanding of how precise present assays are, and which elements of the innovation still require to be enhanced. This understanding assists specify what applications ctDNA sequencing appropriates for and is required prior to ctDNA sequencing can be carried out commonly in medical practice.
In their research study, scientists from 12 getting involved labs in Europe, Asia, and the United States assessed the efficiency of present industry-leading ctDNA assays, from business Roche Sequencing Solutions, Illumina, Integrated DNA Technologies and Burning Rock Dx and Thermo Fisher Scientific.
They evaluated the assays utilizing artificial experiments and mock-ctDNA recommendation samples. Their analysis exposed that all labs spotted ctDNA anomalies above 0.5% relative frequency (constant with late-stage and metastatic growths) with high level of sensitivity, accuracy, and reproducibility utilizing all getting involved assays. However, the assays spotted lower levels of ctDNA (constant with early-stage cancer or early indications of illness regression) unreliably and inconsistently in between various tests.
In their released paper, the scientists detail top priorities for the future advancement of ctDNA assays, which they state will assist advance the innovation for medical applications in keeping an eye on growth development, reaction to treatment, and cancer regression.
“Our findings indicate that the participating ctDNA assays may be suitable for molecular stratification and profiling tumor evolution in advanced cancer patients. This should help clear a path for more advanced clinical trials of ctDNA assays,” states 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.
“Understanding the current assays’ detection limits was a crucial step towards a future where blood tests can be routinely used as a cancer screening tool. This critical study is a thorough analytical evaluation of ctDNA assays, which defined diagnostic limits, assessed reproducibility and identified key experimental variables that impact performance, and which has been called for by government, regulatory and clinical organizations,” states Dr. Joshua Xu from the U.S. FDA National Center for Toxicological Research.
“Our independent performance analysis is a crucial mechanism to drive advances in next-generation sequencing approaches for their use in cancer detection and management. We expect it will help improve the tests’ sensitivity and reliability for diagnosing tumors at early stages,” states co-senior author Associate Professor Tim Mercer from the Garvan Institute and the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland.
Reference: “Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology” by Ira W. Deveson, Binsheng Gong, Kevin Lai, Jennifer S. LoCoco, Todd A. Richmond, Jeoffrey Schageman, Zhihong Zhang, Natalia Novoradovskaya, James C. Willey, Wendell Jones, Rebecca Kusko, Guangchun Chen, Bindu Swapna Madala, James Blackburn, Igor Stevanovski, Ambica Bhandari, Devin Close, Jeffrey Conroy, Michael Hubank, Narasimha Marella, Piotr A. Mieczkowski, Fujun Qiu, Robert Sebra, Daniel Stetson, Lihyun Sun, Philippe Szankasi, Haowen Tan, Lin-ya Tang, Hanane Arib, Hunter Best, Blake Burgher, Pierre R. Bushel, Fergal Casey, Simon Cawley, Chia-Jung Chang, Jonathan Choi, Jorge Dinis, Daniel Duncan, Agda Karina Eterovic, Liang Feng, Abhisek Ghosal, Kristina Giorda, Sean Glenn, Scott Happe, Nathan Haseley, Kyle Horvath, Li-Yuan Hung, Mirna Jarosz, Garima Kushwaha, Dan Li, Quan-Zhen Li, Zhiguang Li, Liang-Chun Liu, Zhichao Liu, Charles Ma, Christopher E. Mason, Dalila B. Megherbi, Tom Morrison, Carlos Pabón-Peña, Mehdi Pirooznia, Paula Z. Proszek, Amelia Raymond, Paul Rindler, Rebecca Ringler, Andreas Scherer, Rita Shaknovich, Tieliu Shi, Melissa Smith, Ping Song, Maya Strahl, Venkat J. Thodima, Nikola Tom, Suman Verma, Jiashi Wang, Leihong Wu, Wenzhong Xiao, Chang Xu, Mary Yang, Guangliang Zhang, Sa Zhang, Yilin Zhang, Leming Shi, Weida Tong, Donald J. Johann Jr, Timothy R. Mercer, Joshua Xu and SEQC2 Oncopanel Sequencing Working Group, 12 April 2021, Nature Biotechnology.
Drs Deveson and Mercer were partly supported by Australia’s National Health and Medical Research Council, the Medical Research Future Fund, Cancer Institute NSW and The Kinghorn Foundation.