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T.D. Azad



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    MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Early Stage NSCLC
    • Presentations: 1
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      MA 13.01 - Clinical and Pathological Variables Influencing Noninvasive Detection of Early Stage Lung Cancer Using Circulating Tumor DNA (ID 8686)

      15:45 - 17:30  |  Author(s): T.D. Azad

      • Abstract
      • Slides

      Background:
      Analysis of circulating tumor DNA (ctDNA) represents a potential strategy for the early detection of lung cancer. Despite significant interest, few studies have evaluated ctDNA levels in early stage lung cancer patients and the feasibility of ctDNA-based screening remains unclear.

      Method:
      We applied lung cancer-focused Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) to assess ctDNA levels in 55 localized lung cancer patients treated with curative intent (stage I: n=22, stage II: n=7, stage III: n=26) and 50 healthy controls. Histological subtypes included: adenocarcinoma (n=30), squamous cell carcinoma (n=19), NSCLC NOS (n=4), and small cell lung cancer (n=2). Sensitivity and specificity of ctDNA detection were evaluated in all patients and in a subset of NSCLC patients with node negative (N0) stage I-II disease. Additionally, for patients with stage I adenocarcinoma in whom ctDNA was not detectable using the standard population-based CAPP-Seq approach, we designed personalized CAPP-Seq assays covering a median of 320 mutations/patient based on tumor exome sequencing from the respective patients.

      Result:
      We detected ctDNA in the pre-treatment plasma of 43/55 (78%) patients at a median allele fraction (AF) of 0.48% (range: 0.004%-26.1%). ROC analysis revealed an area under curve of 0.91, with sensitivity and specificity of 78% and 98%, respectively. Among patients with non-adenocarcinoma histologies, 92% (23/25) had detectable ctDNA (median AF: 0.90%), compared to 67% of patients with adenocarcinoma (20/30; median AF: 0.23%; P=0.046). However, tumor volumes were significantly smaller in adenocarcinomas (P=0.01) and in multivariate analysis ctDNA detection was significantly associated with tumor volume (P=0.01) but not histological subtype (P=0.16). In N0 stage I-II NSCLC patients (n=22), ctDNA was detected in 64% of patients (7/14 adeno vs 7/8 non-adeno) with a specificity of 98% and median AF of 0.022% (median AF of 0.018% vs 0.030% in adeno vs non-adeno patients, respectively). Using personalized CAPP-Seq assays, we detected ctDNA in 3/4 patients with stage I adenocarcinoma in whom ctDNA was not detected using our standard lung-cancer focused CAPP-Seq assay. In these 3 patients, tumor volumes ranged from 11.6-14.7 mL and the ctDNA AF ranged from 0.0014%-0.003%. Taken together, we detected ctDNA in 17/22 (77%) N0 stage I-II tumors.

      Conclusion:
      These data suggest tumor volume is a stronger determinant of ctDNA levels than histology in localized lung cancers. Additionally, our findings suggest that the majority of localized lung cancers shed ctDNA and that ultra-sensitive assays will be required for early detection of lung cancer using ctDNA

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.