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Cheol-Kyu Park



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-014 - Feasibility of Liquid Biopsy Using Plasma and Platelets for Detection of ALK Rearrangements in Non-Small Cell Lung Cancer (ID 9301)

      09:30 - 16:00  |  Presenting Author(s): Cheol-Kyu Park

      • Abstract
      • Slides

      Background:
      Fluorescence in situ hybridization (FISH) using tissue biopsy specimen is the gold standard for detection and confirmation of ALK rearrangement in non-small cell lung cancers (NSCLC), but it is time-consuming and labor-dependent procedure. Liquid biopsy using reverse-transcriptase polymerase chain reaction (RT-PCR) is expected to overcome these limitations, and provide an easy accessibility and frequent assessment of biomarkers. The aim of this study is to investigate the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement.

      Method:
      FISH was performed in 664 patients between January 2015 and May 2017. We retrospectively analyzed the formalin-fixed paraffin-embedded (FFPE) tissue and blood sample to detect ALK rearrangement using multiplex RT-PCR from 30 advanced NSCLC patients who had available tissue specimen and agreed with venous sampling. Total RNA were extracted from FFPE cell blocks, plasma and platelets, respectively. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK, the most common translocation, fusion RNA was detected using PANAqPCR[TM] EML4-ALK fusion gene detection kit.

      Result:
      Twenty-eight patients were FISH positive and two were negative. In a validation data compared with FISH, RT-PCR using FFPE tissue demonstrated 57.1% sensitivity and 69.2% accuracy. Liquid biopsy (plasma or platelets-positive) had higher sensitivity (96.4%) and accuracy (93.3%). Among the specimen of liquid biopsy, platelets showed slightly higher sensitivity and accuracy than plasma (82.1 and 83.3% vs 78.6 and 76.7%). Compared with FFPE tissue using RT-PCR, liquid biopsy showed 100% sensitivity, 20.0% specificity and 69.2% accuracy. Median proportion of positive cells in FISH was higher in subgroups of liquid biopsy with positive result (Plasma, 30.0 vs 15.0%; Platelets 30.0 vs 20.0%), but it was not statistically significant (p=0.062 and 0.104). In 18 patients with crizotinib treatment, platelets-positive subgroup showed a tendency of longer duration of treatment (7.2 vs 1.5 months) and higher response rate (57.1 vs 0.0 %), but the difference was not significant (p=0.071 and 0.100). However, platelets-positive subgroup showed significantly higher disease control rate than platelets-negative subgroup when they were treated with crizotinib (85.7 vs 25.0%, p=0.044).

      Conclusion:
      Plasma and platelets are a valuable source for liquid biopsy using RT-PCR technique in detection of ALK rearrangement, and they could play a supplementary role in diagnosis of ALK-positive NSCLC. Furthermore, platelets, especially, may be useful for predicting the treatment outcome of crizotinib.

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