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Biniam Kidane



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    OA01 - Advanced Diagnostic Approaches for Intrathoracic Lymph Nodes and Peripheral Lung Tumors (ID 117)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 1
    • Now Available
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      OA01.02 - Endobronchial Ultrasound Staging of Operable NSCLC: Triple Negative Lymph Nodes May Not Require Routine Biopsy (Now Available) (ID 2621)

      10:30 - 12:00  |  Author(s): Biniam Kidane

      • Abstract
      • Presentation
      • Slides

      Background

      Current staging guidelines with endobronchial ultrasound (EBUS) still recommend systematic biopsy of at least 3 mediastinal stations prior to surgical resection. Recently, a 4-point ultrasonographic score (Canada Lymph Node Score- CLNS) was developed to determine the probability of nodal metastasis in any given lymph node. A LN with CLNS<2 is considered very low probability for malignancy. We hypothesized that, during EBUS assessment of patients with cN0 non-small cell lung cancer, individual nodal stations that have CLNS<2 do not require routine biopsy because they are likely to represent true pN0 disease.

      iaslc 2019 - clns lymph node figure.png

      Method

      The CLNS is a prospectively validated score that uses four ultrasonographic features to accurately predict LN malignancy. LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. “Triple Negative” LNs were defined as cN0 on CT (LN≤1cm), PET (no hypermetabolic activity) and EBUS (CLNS<2). Specificity, NPV, and false-negative rates were calculated against the gold-standard pathological diagnosis from surgically excised specimens.

      Result

      In total, 122 LNs in 58 cN0 patients were assessed. Triple Negative LNs were associated with the following T-stage distribution (T1a=12.07%, T1b=24.14%, T2a=34.38%, T2b=10.34%, T3=17.24%, T4=1.72%). Triple Negative LNs had a specificity, NPV, and false-negative rate of 86.10% (95%CI: 78.40-91.80%), 93.40% (95%CI: 86.90-97.30%), and 6.60%, respectively when using <2 as the CLNS malignancy cut-off. In total, only 5.74%(n=7) Triple Negative nodes were actually proven to be malignant, 6/7 (85.71%) on EBUS-TBNA, and 1/7 (14.29%) only after surgical resection.

      Conclusion

      Triple Negative LNs have a high NPV for malignancy. At the time of EBUS in cN0 patients, it may be possible that Triple Negative LNs do not require tissue sampling, thereby saving procedural time, cost, and discomfort. Findings also suggest that Triple Negative LNs with inconclusive biopsy results may not require repeat sampling. A prospective comparative trial is required to confirm these findings.

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    P2.11 - Screening and Early Detection (ID 178)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.11-10 - Discovery of Potential Biomarkers That Discriminate Early Stage NSCLC from Controls by Non-Targeted Metabolomics Profiling (ID 1857)

      10:15 - 18:15  |  Author(s): Biniam Kidane

      • Abstract

      Background

      Detection of NSCLC at the early stage is a potential means to reduce mortality and morbidity of lung cancer. Development of an accurate, non-invasive, economical, and safe test to detect early stage NSCLC remains a challenge. We explored metabolomics profiling of plasma to discriminate early stage NSCLC cases from Cancer-Free Controls (CFC).

      Method

      Frozen plasma samples collected from 2004 to 2014 from 250 patients with clinical early stage NSCLC (drawn prior to surgical resection) and 250 CFCs were obtained from a provincial biorepository. Samples were thawed, extracted, and analyzed in duplicate by blinded laboratory personnel using non-targeted Ultra High Performance Liquid Chromatography/Quadrupole Time-Of-Flight Mass Spectrometry (UHPLC-QTOF-MS). Individual metabolic entities were identified and quantified using Mass Profiler Professional Software (Agilent Technologies, CA, USA). Analysis was restricted to known human metabolites identified by the Metlin and Human Metabolome databases. Candidate metabolites quantified in less than 20% of samples were dropped; missing values were replaced with one-half of the smallest measurement for each metabolite. Final candidate metabolites were screened for differential abundance (DA) between NSCLC cases and CFCs using: (1) False discovery rate (FDR)-adjusted p-values less than 1% after controlling for age, sex and smoking status in linear regression; (2) <1% change in DA due to covariates; (3) up-regulation in NSCLC.

      Result

      Of the 250 NSCLC Cases, 185 (74%) had adenocarcinoma, 65 (26%) had Squamous Cell Carcinoma; 204 (81.6%) had pathological Stage I/II disease (AJCC 7th ed) and 46 (18.4%) had stage III/IV disease. Median age was 70 (range 46-88) in NSCLC cases and 56 (20-89) in CFCs (p<0.001), and NSCLC cases had more males compared to CFCs (46.4% vs 31.2%, p <0.001). NSCLC patients had a higher proportion of current (27.2% vs 6%) or ex-smokers (64.8% vs 20.8%) compared to CFCs (p<0.001).

      A total of 1,209 known human metabolites were detected using UHPLC-QTOF-MS technique, of which 676 were present in a minimum of 80% of all samples and were used for modeling. Table 1 lists candidate metabolomics biomarkers strongly upregulated in NSCLC cases versus CFCs which were unaffected by covariates of age, sex, and smoking. A multiple logistic regression model using the top 3 metabolites correctly classified NSCLC case from CFC with an overall accuracy of 93.6% and an area under the curve of 0.975.

      table 1 snippet no compression.png

      Conclusion

      Metabolomics profiling of plasma represents a potential means to distinguish NSCLC cases from CFCs. Further targeted metabolomics analyses of specific classes of metabolites in larger cohorts are warranted.