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Dongmei Lin



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    MA 15 - Lung Cancer Biology II (ID 670)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 15.04 - Detection of ALK Rearrangements in Non-Small-Cell Lung Cancer (NSCLC) Patients by Liquid Biopsy (ID 8969)

      15:45 - 17:30  |  Presenting Author(s): Dongmei Lin

      • Abstract
      • Presentation
      • Slides

      Background:
      The ALK rearrangement (ALK+) is an important actionable genetic aberration of NSCLC, which is associated with high sensitivity to targeted agents such as crizotinib and alectinib. Currently, ALK+ is mainly detected by fluorescent in situ hybridization (FISH) or immunohistochemistry that strictly require the availability of tumor sample, however, in NSCLC, tumor tissue are not always valid or sufficient for testing and non-invasive analyzing methods are urgently needed. Recent years, next generation sequencing (NGS) based liquid biopsy has emerged as a useful complementary technique for the analysis of cancer genetic profile, in the present study, we aimed to evaluate the performance of liquid biopsy for the detection of ALK rearrangements in NSCLC.

      Method:
      From January 2016 to May 2017, paired tumor and cell-free plasma samples were collected form 360 histologically proven NSCLC patients. The presence of ALK+ was detected by fluorescent in situ hybridization (FISH) in tumor samples and by a NGS based liquid biopsy technology that targeted 96 genes, including ALK, in plasma samples. Genomic alterations in cancer-associated somatic variants are analyzed by massively parallel sequencing. The FISH results were set as golden-standard for the presence of ALK+. The specificity and sensitivity of liquid biopsy for the detection of ALK+ were evaluated.

      Result:
      ALK+ were detected in 28/360 (7.8%) of the tumor samples and 25/360 (6.9%) of the plasma samples. All the 25 ALK+ plasma samples were also ALK+ in their corresponding tumor samples. Liquid biopsy failed to detect ALK+ in 3 samples that were positive in tumor sample. Thus, the specificity and sensitivity of liquid biopsy for detection of ALK+ in plasma were 100% and 89.3%, respectively.

      Conclusion:
      NGS based liquid biopsy technology is a promising, non-invasive method for the detection of ALK rearrangement that may benefit NSCLC patients who have difficult to obtain tumor samples or need continuous monitor of ALK status.

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    MA 18 - Global Tobacco Control and Epidemiology II (ID 676)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Epidemiology/Primary Prevention/Tobacco Control and Cessation
    • Presentations: 1
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      MA 18.13 - Mutation Profile of EGFR Gene in Chinese Patients with Non-Small-Cell Lung Cancer (NSCLC): An Analysis of 2,666 Cases (ID 8974)

      15:45 - 17:30  |  Presenting Author(s): Dongmei Lin

      • Abstract
      • Presentation
      • Slides

      Background:
      Mutations of epidermal growth factor receptor (EGFR) gene have been proved as the strongest predictor of response to EGFR-tyrosine kinase inhibitor (TKI) treatment in NSCLC. Currently, 7 most common somatic mutations of EGFR have been reported, among which, L858R and exon 19 deletion theoretically confer sensitivity to EGFR TKIs, other primary EGFR mutations may confer resistance. The EGFR mutation profile showed significant geographical differences (about 35% in East-Asia and 10% in Caucasian population) but very limit data have been reported from China. In addition, we carried liquid biopsy and next generation DNA sequencing analysis on 180 samples from NSCLC patients. We hereby reported the mutation profile EGFR gene in a large scale, real world cohort of 2,666 Chinese NSCLC patients.

      Method:
      From January 2016 to June 2017, 7 primary EGFR mutations (L858R, Exon 19 del, G719X, L861Q, Exon 20 ins, S768I and T790M) were assayed in tumor tissue (paraffin-embedded or fresh) of 2,666 Chinese patients with NSCLC by a commercial TaqMan PCR kit (Human EGFR Gene Mutations Detection Kit(ACCB)). For liquid biopsy analysis, cell-free DNA is extracted from plasma, a panel of 96-targeted genes was assayed, and genomic alterations in cancer-associated somatic variants are analyzed by massively parallel sequencing.

      Result:
      Among the 2,666, 1,601(45.9%) were female and 1,447(54.1%) were male, 2,446 (91.7%) had adenocarcinoma (ADC) and 220(8.3%) had squamous carcinoma (SC).The median age of patients was 63 yr (range 17yr-91yr). The detailed EGFR mutation profile was shown in Table 1, the overall incidence of EGFR mutation was 1,319(49.5%). Compare to female patients, male patients showed significant lower rate of EGFR mutation (67.2% vs. 34.6%, p<0.01). More than 50% of patients with ADC showed EGFR mutation while the rate was only 10% in patients with SC. Exon 19 del and L858R, 2 markers for potential better response of TKI, account for the vast majority of all the EGFR mutations. We found the mutation profiles from samples analyzed by NGS is similar to those analyzed by PCR method.

      Conclusion:
      In Chinese NSCLC female patients with lung adenocarcinoma, exon 19 del and L858R represented more than 90% of the total EGFR mutations, thus, for those whose EGFR status was unable to be determined, direct TKI treatment many has an odd of 60% to benefit the patients. About 5% of SC patients also showed exon 19 del and L858R mutation which means they could be subjects for TKI treatment.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.