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C. Zhao



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    MINI 10 - ALK and EGFR (ID 105)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI10.02 - Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Co-Altered Lung Adenocarcinoma (ID 685)

      16:45 - 18:15  |  Author(s): C. Zhao

      • Abstract
      • Presentation
      • Slides

      Background:
      Genetic intratumoral heterogeneity has a profound influence on the selection of clinical treatment strategies and addressing resistance to targeted therapy. The purpose of our study is to explore the potential effect of intratumoral heterogeneity on both the genetic and pathologic characteristics of ALK-rearranged lung adenocarcinoma (LADC).

      Methods:
      We tested ALK fusions and EGFR mutations in 629 LADC patients by using laser capture microdissection (LCM) to capture spatially separated tumor cell subpopulations in various adenocarcinoma subtypes and test for ALK fusions and EGFR mutations in ALK-rearranged, EGFR-mutated, and ALK/EGFR co-altered LADCs in order to compare the oncogenic driver status between different tumor cell subpopulations in the same primary tumor.

      Results:
      Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and 2 had ALK fusions coexisting with EGFR mutations. Intratumoral heterogeneity of ALK fusions was identified in 9 patients by RT-PCR. In the 2 ALK/EGFR co-altered patients, intratumoral genetic heterogeneity was observed both between different growth patterns and within the same growth pattern. Genetic intratumoral heterogeneity of EGFR mutations was also identified in EGFR-mutated NSCLC. ALK fusions were positively associated with a micropapillary pattern (P=0.002) and negatively associated with a lepidic pattern (P=0.008) in a statistically-expanded analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.

      Conclusion:
      Intratumoral genetic heterogeneity was demonstrated to co-exist with histologic heterogeneity in both single-driver and EGFR/ALK co-altered LADCs. As for the latter, one of the dual altered drivers may be the trunk-driver for the tumor.

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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-010 - EML4-ALK Fusion Detected by qRT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced NSCLC (ID 2338)

      09:30 - 17:00  |  Author(s): C. Zhao

      • Abstract
      • Slides

      Background:
      Quantitative reverse transcriptase polymerase chain reaction assay (qRT-PCR) has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by qRT-PCR.

      Methods:
      Patients with advanced NSCLC who had their ALK rearrangement status detected by qRT-PCR were included in this analysis. The utility of qRT-PCR and fluorescence in situ hybridization assay (FISH) were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.

      Results:
      1010 patients were included in this study. Among them, 104 patients were ALK qRT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases which were missed by FISH. The overall response rate (ORR) and median progression free survival (mPFS) of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95%CI, 47.2-73.6) and 8.4 months (95% CI 6.75-10.05) respectively, which were similar to the 21 patients detected by FISH with ORR of 57.1% (95% CI 33.3-76.2) (p=0.799) and mPFS of 7.4 months (95% CI 4.43-10.38) (p=0.833) after crizotinib treatment. Interestingly, there were 2 patients responded to crizotinib had their ALK rearrangement detected by qRT-PCR but not FISH.

      Conclusion:
      qRT-PCR should be considered as an alternative assay to detect ALK fusion oncogene in NSCLC patients who might be benefit from crizotinib treatment.

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