Author of

• 20183

  +

  P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Clinical Design, Statistics and Clinical Trials
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 24086

    +

    P3.04-010 - Validation of a ctDNA Methylation Assay to Differentiate Benign and Malignant Pulmonary Nodules: A Chinese Nationwide Multi-Center Study (ID 10039)

    09:30 - 09:30  |  Author(s): X. Zhi
    • Abstract

    Background:
    Current state-of-the-art lung cancer early screening utilizes low-dose CT scan to identify lung nodules smaller than 3 cm in diameter. However, it's still a clinical challenge to differentiate between malignant and benign nodules. In previous studies, we had taken the approach of methylation profiling by high- throughput bisulfite DNA sequencing to learn methylation patterns that differentiate malignant vs. benign lesions from tissue samples by in-depth data mining, and then used pattern matching to classify plasma samples. We were able to achieve a preliminary sensitivity of 94.3% for identification of malignancies, with a preliminary specificity of 93.6% against all benign specimens in the training set (129 malignant specimens and 101 benign specimens). From an independent validation set of 145 plasma samples (79 malignant specimens and 66 benign specimens from asymptomatic normal individuals and patients), this assay obtained a preliminary sensitivity of 78.5% and a preliminary specificity of 83.3% for differentiating patients with malignant tumor. Specifically, the assay is demonstrated to be highly sensitive towards early‐stage lung cancer detection, with a preliminary sensitivity of 71.1% in 38 patients with stage Ia lung cancer and 87.5% in 16 patients with stage Ib lung cancer. In this multi-center clinical study, we aim to validate the accuracy of ctDNA methylation test for diagnosing early-stage lung cancer by comparing the pre-operational ctDNA methylation test results with the surgical pathology results. (NCT03181490，CCTC-1701)
    
    Method:
    Patients who are diagnosed with solitary pulmonary nodules (<=3cm) by LDCT/CT scans and have decided to undergo surgery will be recruited in this study. All blood samples are collected before surgery. We take the approach of targeted methylation profiling by high-throughput bisulfite DNA sequencing of plasma samples to identify lung cancer specific methylation signatures. By comparing the results of the methylation test and the histopathological diagnostic results, we calculate the specificity and sensitivity of the methylation test on differentiating patients with malignant lesions from benign diseases. The laboratory technicians and analysts who perform the methylation tests are blinded to this study. Sample size determination: expected specificity and sensitivity is 80% based on pre-clinical study, permissible error is ±5%, α=0.05, β=0.10. According to the study design, patients with benign nodules make up ~20% of all patients. Therefore, the estimated sample size for each of the benign and malignant group is estimated to be at least 246.
    
    Result:
    Section not applicable
    
    Conclusion:
    Section not applicable