On April 28, 2022, Bristol Myers Squibb (BMS), the world's top international pharmaceutical company in the field of oncology and hematology, published a PLOS ONE article online, officially releasing the results of its large panel head-to-head test evaluation that invited five of the world's top liquid biopsy companies to participate. Huidu Medical's 600 gene Predicine ATLAS new generation liquid biopsy technology with excellent sensitivity, specificity, accuracy, repeatability and high performance under low starting cfDNA volume conditions, the best performance in all liquid biopsy technology evaluation indicators, perfectly surpassing the technology platform of four other well-known european and American large companies, the overall performance ranks first in the international industry.
As the world's first approved PD-1 inhibitor, BMS's Opdivo (O drug) has been approved for clinical use for many indications and benefited many oncology patients worldwide. BMS is also a leader in the application of liquid biopsy in oncology drug research. Liquid biopsy based on blood and other body fluids has the advantages of minimally invasive or non-invasive, overcoming tumor heterogeneity, repeatable detection, dynamic monitoring, can achieve minimal residual disease (MRD) monitoring and early tumor screening, etc., clinical accessibility and future application prospects are higher than tissue biopsy, but limited by technical means, further optimization and verification are needed in terms of detection sensitivity, specificity, accuracy and stability. Choosing a reliable, accurate liquid biopsy product is key to bringing more benefits to patients.
In this study, the BMS North America team selected five internationally leading and widely used large panel liquid biopsy products in Europe and the United States. Huidu Medical's Predicine ATLAS cfDNA 600 gene test is one of the Assay B, and it is also the only liquid biopsy technology platform that can reliably detect cfDNA copy deletion. The two sets of standard samples in the assessment simulated cfDNA samples from solid tumors and clinical plasma samples from myeloid tumors, and added special mutation types such as long fragment insertion/deletion, repeat sequence region mutations, and gene deletions, and were validated and evaluated from four genetic mutation abundances (VAFs) close to clinical practice: 1%, 0.5%, 0.125%, and 0%.
*Note: Assay B is the Predicine ATLAS of the Huidu Medical 600 gene.
Huidu medical technology proves for the first time that high sensitivity, high specificity (low false positive rate), and low starting cfDNA amount can be achieved simultaneously.
In the clinical practice of liquid biopsy, sensitivity, specificity and sample demand have been difficult to achieve balance for a long time. High sensitivity is a guarantee that low-frequency mutations do not miss tests, while low false-positive rates help patients seize the treatment opportunities that are truly beneficial, avoiding the waste of treatment costs and valuable treatment time windows, and the technical mutual "checks and balances" seem to have caused a situation in which sensitivity and false-positive rates are difficult to complete. In order to take into account the sensitivity and false positive rate, the requirements for the initial cfDNA input are transformed into strict requirements for the amount of plasma samples drawn by patients and the content of tumor cells in clinical practice. A significant proportion of patients who fail to provide adequate sample sizes miss out on testing opportunities and miss valuable possible treatment windows.
In the evaluation of the most technically challenging cfDNA low metering and extremely low detection limit, Huidu Medical's liquid biopsy products show excellent sensitivity and specificity.
The evaluation compared the performance of each product by different detection initiations and detection mutation frequency (VAF) for the two most important indicators in the clinical application of liquid biopsy, sensitivity and specificity (low false positive rate). When using the recommended detection starting amount (30 ng or 50 ng cfDNA) of each product, the detection of VAF gene mutations greater than or equal to 0.5% of the five products showed very good sensitivity and good specificity, and the overall performance was significantly higher than that of previous parallel comparative evaluations, such as SEQC2 studies.
But when the VAF reached the "challenge zone" below 0.5%, the performance of the different panels began to show significant differences. When the VAF is 0.125%, Huidu Medical (assary B in the figure) is the best sensitivity NGS liquid biopsy panel, both in the solid tumor standard sample group or in the myeloid tumor standard sample group: when the VAF is 0.125%, the sensitivity (solid tumor group) is > 95%, and the sensitivity (myeloid tumor group) is 100%.
A) Solid tumor 30 or 50 ng starting DNA; B) solid tumor 10 ng starting DNA; C) myeloid tumor 30 or 50 ng starting DNA; D) myeloid tumor 10 ng starting DNA
Because in actual clinical practice, especially in the plasma of some patients in the early stage of cancer or after radical resection, it is often not possible to collect the recommended amount of cfDNA (30 ng or 50 ng) for genetic testing. Huidu Medical's liquid biopsy technology has developed solutions specifically for this real-world challenge, optimized from all angles of experimentation and analysis, and shined in this comparison.
Under the condition of a starting amount of 10ng, when the VAF reaches less than 0.5%, the sensitivity of other products has decreased sharply compared with Huidu Medical Technology. When the VAF is 0.125%, only Huidu medical products have a sensitivity of more than 90%, maintaining the highest. It is worth mentioning that Huidu Medical is the only product that has not had a "false positive" under all evaluation conditions. It perfectly solves the sample problem in clinical trials and clinical practice, improves the success rate of detection while ensuring the sensitivity and specificity of the detection, and brings accurate and sensitive tumor molecular diagnosis to patients.
Huidu Medical Technology achieves high uniformity and accuracy without the need for comparisons – the technical guarantee of accurate detection of copy number variation and non-invasive customized MRD.
CtDNA includes a large number of low-abundance gene variants and background noise mutations, how to minimize background noise, detect the signal of a tumor cell from a million normal cells, has always been the technical bottleneck of clinical applications of liquid biopsy, which also makes "do you need control?" What is the panel sequencing depth? Become a frequently mentioned issue when clinical experts pay attention to liquid biopsy techniques.
Huidu Medical's liquid biopsy products are based on technology optimization and always maintain the highest effective coverage of mutation sites in the evaluation products. This is the basis for huidu medical liquid biopsy products to achieve excellent performance.
Comparing the average VAF obtained by the test with the expected VAF, Huidu Medical's liquid biopsy technology is one of the best performing products under the conditions of conventional starting amount of 30ng and low starting amount of 10ng, especially when the VAF is as low as 0.125%, Huidu medical results are the best, the effective sequencing depth is the deepest, and it has extremely high accuracy and extremely high uniformity. Such performance can not only accurately detect gene mutations in cfDNA (SNV and InDel), but also further analyze gene copy number amplification (CNA) and copy number deletion (CNR, copy number reduction), providing accurate molecular detection for targeted drugs with copy number variation as biomarkers, benefiting patients.
Huidu Medical's liquid biopsy products are based on a proprietary bioxin algorithm that accurately filters more than 95% of background noise mutations without germline control. In the case of thousands of background noise mutations detected in other entries, Huidu Medical Products maintained an extremely low number of background noise mutations, demonstrating a huge technological lead.
With the expansion of the clinical practice application of liquid biopsy, especially the in-depth study of immunotherapy-assisted biomarker - tumor mutation load (TMB) and tiny residual lesions (MRD), accurately finding tumor mutations from complex background noise mutations is an important trend and technical consideration for future clinical applications. The study also compared the background noise mutation detection and processing capabilities of the participants, and Huidu Medical's liquid biopsy technology can effectively eliminate 95% of the background noise, thus winning overall. On the one hand, it explains why Huidu medical detection products show extreme sensitivity and specificity, and on the other hand, it also provides reliable bio-information and product performance proof for the technology in a wide range of clinical applications such as TMB and MRD.
In recent years, Huidu Medical has cooperated with the world's top ten international pharmaceutical companies in the field of clinical trials and CDx concomitant diagnosis, and published a series of research results in top international academic journals. The results of the liquid biopsy study of Huidu Medical and AstraZeneca were published in Gastroenterology & Hepatology, a Lancet sub-journal with an impact factor of nearly 20 points, which verified the feasibility of ctDNA mutation abundance after treatment as a biomarker for evaluating the efficacy of immunotherapy combined with chemotherapy, laying a foundation for the application of clinical prognosis assessment.
Adhering to the practice standard of "the starting point is the apex of the industry", Huidu Medical has honed a new generation of liquid biopsy technology that attracts global attention and is the world's premier after seven years of meticulous work.
"I am very pleased to see BMS's public recognition and industry endorsement of Huidu Medical's liquid biopsy technology." Dr. Jia Shidong, founder and global CEO of Huidu Medical, said, "In the era of precision medicine, liquid biopsy will greatly promote the clinical trial of new tumor drugs and the personalized clinical treatment of patients, and realize the company's vision as soon as possible: to send the best hospitals to every village and the best doctors to every family." ”
Original English text:
Direct comparison of circulating tumor DNA sequencing assays with targeted large gene panels
Huidu Medical is a high-tech group company focusing on precision medicine. Adhere to the industry standard of "the starting point is the apex of the industry" and create a fine product in the liquid biopsy industry.
Starting from European and American pharmaceutical companies, Huidu Medical Industry's original ctRNA + ctDNA combined liquid biopsy technology, global solutions for precision clinical trials and CAP and CLIA laboratory network operating simultaneously in China and the United States have cooperated with the world's top ten European and American pharmaceutical companies and top experts and medical institutions at home and abroad to support global new drug clinical trials, accompanying diagnostic development and cancer early screening through a one-stop biomarker platform system based on blood, urine and organization.
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