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Jin-Shing Chen



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    FP09 - Screening and Early Detection (ID 175)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP09.03 - Circulating Nucleosomes in Lung Cancer Diagnosis Following Low-Dose Computed Tomography (ID 3748)

      00:00 - 00:00  |  Author(s): Jin-Shing Chen

      • Abstract
      • Slides

      Introduction

      Low-Dose Computed Tomography (LDCT) is the widely accepted standard for screening of individuals at high risk of lung cancer (LC). However, LDCT has several limitations including the high prevalence of non-malignant pulmonary nodules detected leading to overdiagnosis, the potential harms of cumulative radiation dose and poor adherence to recommended follow-up. Therefore, novel blood-based tests could offer a simple follow confirmation approach or front-line stratification test to help discriminate between lung cancer and non-malignant nodules noted by LDCT.

      Nucleosomes are DNA fragments wrapped around a histone core and have been associated with tumour burden and malignancy progression. We used a Nu.Q™ immuno-assay to investigate the clinical performance of circulating nucleosome levels containing the histone H3.1 alone and in combination with carcinoembryonic antigen (CEA) in blood from subjects referred to LDCT to evaluate their discriminant power towards LC and non-malignant nodules.

      Methods

      We measured H3.1 variant nucleosome levels and CEA in 220 patients referred for CT at National Taiwan University Hospital. The patients were later confirmed to have either a LC (n=100) (70 early stage, 30 late stage), or non-malignant nodules (n=50), or no-nodules (n=30). Whole blood was collected in EDTA plasma tubes for analysis by Nu.Q™ immunoassay. Plasma samples were analyzed in duplicate for nucleosome levels using a quantitative immunoassay for H3.1 nucleosomes (Nu.Q™-H3.1) developed and validated to CLSI guidelines using a recombinant nucleosome standard curve. CEA was analysed using a chemiluminescent magnetic microparticle immunoassay on the Abbott ARCHITECT analyzer. We evaluated circulating Nu.Q™-H3.1 and CEA levels individually for their performance in discriminating subjects into the following groups: cancer vs non-malignant nodule and no nodules (group A) or cancer vs non-malignant nodules (group B). A decision tree analysis was performed for combinatorial performance in discriminating group B.

      Results

      Nu.Q™-H3.1 gave an area under the curve (AUC) of 0.60 and 0.59 for group A and B, respectively, with a sensitivity at 90% specificity of 16% and 23% for group A and B, respectively. CEA gave an AUC of 0.65 and 0.60 and a sensitivity at 90% specificity of 28% and 26% for group A and B, respectively. A decision tree combining Nu.Q™ H3.1 with CEA resulted in improved discrimination between LC and non-malignant nodules (group B) relative to CEA marker alone, achieving a sensitivity of 41% at 90% specificity for the key clinical question faced by physicians utilizing LDCT. In addition, we observed that whereas CEA detect mostly late stage cancer, H3.1 levels detect better early stage cancer.

      Conclusion

      Our results indicate that nucleosome levels, as measured by Nu.Q ™-H3.1, are elevated in LC. Combining analysis with CEA exceeds the performance either biomarker alone and provides a discrimination power between LC vs non-malignant nodules in LD-CT screen positive individuals. These promising initial results suggest that the Nu.Q™ H3.1 assay may be a useful alternative blood-based test in addition to LD-CT for early identification of lung cancer and warrants further study.

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