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Wenhua Liang
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P1.06 - Epidemiology/Primary Prevention/Tobacco Control and Cessation (ID 692)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.06-019 - The Association Between HPV Presence and EGFR Mutations in Asian Patients with NSCLC: A Meta-Analysis (ID 10108)
09:30 - 09:30 | Author(s): Wenhua Liang
- Abstract
Background:
The etiology of non-smoking NSCLC remains largely unknown. It has been widely proved that human papillomavirus (HPV) participate in the development of various cancers unrelated to smoking. Epidermal growth factor receptor (EGFR) mutation patients represent a large part of non-smokers with NSCLC. We performed this meta-analysis to evaluate whether HPV infection in NSCLC tissue is associated with EGFR mutation compared with HPV negative controls.
Method:
MEDLINE, EMBASE, PubMed and Web of Science were searched through June 2017, using the search terms “lung cancer”, “human papillomavirus”, “HPV”, “epidermal growth factor receptor”, “EGFR” and their combinations. We included studies in which HPV detection was based on PCR methods. Association was tested using odds ratio (OR) with 95% confidence intervals (95%CI). Heterogeneity was assessed using Q and I[2] statistic.
Result:
Finally, three studies with a total of 288 patients from Asian countries were identified as eligible publications. The presence of EGFR mutation was significantly related to HPV DNA compared with HPV negative controls (57% vs. 27%,OR 3.91, 95% CI 1.85 to 5.50; p<0.001), with no statistical heterogeneity among studies (I[2]=0; p=0.525).
Conclusion:
Our results suggest that HPV may contribute in part to EGFR mutations in non-small cell lung cancer, at least in Asian population.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-008 - Non-Invasive Diagnosis of Solitary Pulmonary Nodules Using High-Throughput Targeted DNA Methylation Sequencing of Circulating Tumor DNA (ID 9178)
09:30 - 09:30 | Presenting Author(s): Wenhua Liang
- Abstract
Background:
It remains a great challenge to differentiate solitary pulmonary nodules which might cause excessive medical care and unnecessary psychological burden. Disadvantages of previous image-based or invasive methods call for better diagnostic tools .
Method:
Based on several cohorts, we performed methylation profiling by high throughput bisulfite DNA sequencing in tissue samples to learn methylation patterns that differentiate cancerous from benign lesions by in-depth data mining. Then we filtered out methylation patterns exhibiting high background in cfDNA for plasma sample classification. Notably, given the usual low amount of ctDNA in plasma, we developed an ultra-sensitive library preparation method (AnchorIRIS[TM]) to perform targeted bisulfite DNA sequencing from as low as 1 ng of cell free DNA (cfDNA) or 1 mL of plasma.
Result:
In the training set (n = 230) which includes 129 malignant specimens with different subtypes (invasive adenocarcinoma, MIA, AIS, squamous carcinoma, small cell and large cell lung cancer) as well as 101 benign specimens in different categories (hamartoma, granuloma/tuberculosis, inflammation and infections), we were able to achieve a preliminary sensitivity of 94.3% ± 4.3% for identification of maglignacies, with a preliminary specificity of 93.6% ± 4.9% against all benign specimens. From an independent validation set of 145 plasma samples, this assay obtained a preliminary sensitivity of 78.5% and a preliminary specificity of 83.3% for differentiating patients with malignant tumor (n = 79) from patients with benign lesions and asymptomatic normal individuals (n = 66). Specifically, our 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. To further confirm the clinical application of this model, an additional validation study was carried out in an independent center. Our assay obtained an overall sensitivity of 89.2% for 37 malignant tissue samples, particularly with a sensitivity of 100% for adenocarcinoma, and an overall specificity of 85.7% for 21 benign tissue samples. For plasma samples, our assay achieved a sensitivity and a specificity of 80% and 66.7% respectively for 20 malignant and 3 benign samples.
Conclusion:
We have developed a highly sensitive blood based non-invasive diagnostic assay for differentiation of solitary pulmonary nodules, which can aid clinical decisions for patients with a CT scan positive for lung nodules. To the best of our knowledge, this is the first study to examine the diagnostic value of high throughput targeted DNA methylation sequencing for early stage lung cancer.
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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)
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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 | Presenting Author(s): Wenhua Liang
- 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:
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Conclusion:
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