Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
A WGS-Based Hyper-Accurate Method for Lung Cancer Screening and Postoperative MRD Detection
43 Pages Posted: 2 Sep 2022
More...Abstract
Background: Liquid biopsy is a promising non-invasive alternative for cancer screening and MRD detection, although there are some concerns regarding its clinical application.
Methods: To evaluate its efficiency in detecting lung cancer (LC), we applied a modified WGS-based HIFI method for LC screening and postoperative MRD detection by combining the hyper-co-methylated read approach and the circulating single-molecule amplification and resequencing technology (cSMART2.0).
Findings: For early screening of LC, the LC score model was constructed using the support vector machine method, which showed satisfactory sensitivity at a high specificity of 98% and achieved an area under the curve of 0.912 in the validation set comprising 306 participants prospectively enrolled from multiple centers. The LC score model outperformed other models. Especially for stage I patients, the LC-score model achieved a sensitivity of more than 60% at a specificity of 90.8%. When applied the HIFI model to the real social population, an NPV of 99.92% was achieved in the Chinese population at 0.15% prevalence. Additionally, the MRD detection rate improved significantly by combining WGS and ctDNA detection, with a sensitivity of 74.00% at the same high specificity (98%).
Interpretation: In conclusion, the HIFI method is promising for the diagnosis and treatment of LC.
Trial Registration: This study was registered on Clinical Trails.gov (NCT04558255).
Funding: This study was supported by Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences（2021RU002), National Natural Science Foundation of China (No.82072566), Peking University People's Hospital Research and Development Funds (RS2019-01) and Daxuesheng Chuangxin Shiyan Project of Peking University Health Science Center.
Declaration of Interest: Wendy Wu, Wenjie Liu, Hao Yang, Airong Yang and Xueying Zhang are the employee of Berry Oncology Corporation. The other authors declare that they have no competing interests.
Ethical Approval: All procedures were approved by the Medical Ethics Committee (2019PHB058-02) of the Peking University People’s Hospital. Informed consent was obtained from all enrolled participants prior to participation.
Keywords: liquid biopsy, WGS, lung cancer, diagnostic model, prognostic model
Suggested Citation: Suggested Citation