Collaborator presented AccuraGen's ctDNA-NGS kit validation at AACR

On April 15, the American Association for Cancer Research (AACR) 2018 annual meeting of the liquid biopsy sub-forum (mini symposium: liquid biopsy 1) gathered lots of experts and scholars all around the world, as well as the well-known firms including Guardant Health, Inivata, Dana-Farber Cancer Institute. Many excellent speeches were delivered. The speech introducing EGFR/ KRAS / BRAF ctDNA-NGS multi-center performance validation for lung cancer that as the only research project presented by Chinese experts, was the most attractive one among them.

The study was conducted by Professor Jiatao Lou, director of the Chest Hospital (Affiliated of Shanghai Jiao Tong University), together with xperts from the Tumor Center ofthe First Hospital of Jilin University and the Cancer Radiology Department of the Cancer Hospital of Zhong Shan University. The performance of the kit has been evaluated comprehensively according to results of plasma digital PCR and tissue ARMS simultaneously on clinical samples from multi-centers.  In the meeting, Professor Lou explained in detail the pioneering significance of this study.

Q: Professor Lou, what is the main reason for this study to beselected as an oral speech by the AACR Expert Committee?

A: I think our research is closely related to the pain points in the current clinical application of ctDNA testing. Recently, from a joint review by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP), the clinical application of ctDNA is not mature enough. The main reason is that many clinical applications based on ctDNA have not been sufficiently validated even for the intended clinical application. This is not accpetable for traditional medical testing projects.

Our team went back to the fundamentals of medical testing of ctDNA detection. We focused on the accuracy and clinical effectiveness, and carefully validated the performance of the kit, using a variety of methods for side-by-side comparisons. Only in this way, we can effectively consider whether a technical platform is accurate and reliable, and further discuss the clinical value and significance of medical testing based on this platform. I am glad that our efforts in the fundamentals of a clincal test were recognized by AACR expert committee.

Q: What do you think is the practical significance of this study for the clinical application of ctDNA in China?

A: This study is only a pilot study. We have many colleagues explore a model for establishing high-performance ctDNA-NGS detection capabilities in hospitals. In this study, we highlighted laboratory performance validation based on standard materials (sensitivity, specificity, LOD, etc.) and clinicalperformance validation based on clinical samples, taking into account thefuture detection of various clinical application situations in the world. Theseresearch ideas are based on the perspective of laboratory medicine. I thinkthis is the greatest affirmation of this work if it can provide some referencefor similar work and help to improve the standardization and repeatability ofclinical verification procedures for liquid biopsy.

Q: What is your outlook on the future application of ctDNA-NGStechnology in clinical practice?

A: ctDNA-NGS is a new technology with great potential in clinicalapplication. I believe this technology will help precision medicine in manydirections after achieving standardization and standardization. As a leadinglung cancer diagnostic and therapeutic institution in China, we focus on theprospective development of new molecular diagnostic techniques for thedetection of lung cancer. I do believe the medical laboratories withprofessional staff and equipment will have sufficient incentive to carry out thetests independently in future. They will ensure higher quality control of thetesting process, and effective accumulation of testing data. Meanwhile, thetesting costs will reduce and the turnaround time will be shortened in order toachieve ultimate better results and to serve clinicians and serve patients.

Abstract of speech

This study assessed the sensitivity, specificity and LOD of thecfDNA-based assay using the Accu-Kit™ EGFR / KRAS /BRAF amplifier sequencing kit. The plasma samples from 134 patients withnon-small cell lung cancer and 50 healthy controls were analyzed cfDNA, and thetumor tissue ARMS technique and the results of the same blood sample ddPCRtechnique were compared. The results showed that when the sample size of cfDNAwas 20 ng and the AF value (allele frequency) was 0.1%, the common mutation ofEGFR was detected with an average detection rate of 100%, and no false positivewas detected in all blank control samples. On the comparison of tissue andplasma assay, the concordance of EGFR mutation was 94% between the pre-treatmentplasma ctDNA detection by NGS and the matched tissue gDNA-detection by ARMS,and the concordance of EGFR mutation was 98% between the pre-treatment plasma ctDNAdetection by NGS and the ctDNA-detection by ddPCR. In terms of quantitativeaccuracy, the AF concordance (R²) of ctDNA-NGS is 0.95 comparedwith ddPCR. This study also found that detection of de novo mutation 19 Indel that multiple PCR methods cannot detectedfully reflects the advantages of ctDNA-NGS.