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J. Wang



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    MA17 - Genetic Drivers (ID 409)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      MA17.03 - Identifying Genomic Alteration and Inter-Tumor Heterogeneity of Multiple Primary Lung Cancers by Targeted NGS of Tumor Tissue and ctDNA (ID 4616)

      14:32 - 14:38  |  Author(s): J. Wang

      • Abstract
      • Presentation
      • Slides

      Background:
      Evidence supports the existence of genomic discrepancy in multiple primary lung cancers (MPLC). This study identified genomic alterations of MPLC by targeted next-generation sequencing (NGS) and assessed whether inter-tumor heterogeneous somatic mutations could be detected in circulating tumor DNA (ctDNA).

      Methods:
      94 tumor samples originating from 45 clinically considered multiple primary lung cancer patients (including multiple solid tumors and multifocal tumors) were available for genomic alteration analysis (NCT02833467). DNA and RNA were extracted from fresh tumor tissue or formalin-fixed, paraffin-embedded tissue. 143 cancer-related genomic alterations including single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs) and gene rearrangements were identified by Oncomine Comprehensive Panel (OCP), Ion Torrent techniques. High frequency clinical relevant mutations (EGFR, KRAS, BRAF, PIK3CA) were identified in circulating tumor DNA by droplet digital PCR (ddPCR).

      Results:
      The median age of the patients was 61 years and 71% were female. 91% patients were stageⅠ. Molecular analysis performed with a good quality. One hundred and thirty-six mutations and twenty four fusions were detected. Alterations were found in 81 of the 94 lesions (86%), involving EGFR (50.0%), TP53(10.6%), KRAS (8.5%), BRAF (4.3%), ERBB2 (4.3%), PIK3CA(2.1%),PTEN(2.1%),ALK (2.1%),ROS1 (1.1%), RET (7.4%), NF2(2.1%), CDKN2A(2.1%), APC(5.3%), ATM(5.3%),etc. Forty-two (93.3%) patients harbored discordant gene distribution between multiple tumors. CNVs were much higher in patients with more than 2 lesions. Forty-eight lesions harbored detectable somatic mutations by ddPCR, in which 30(62.5%) lesions were identified positive in circulating tumor DNA. 76.9% (20/26) solid dominant lesions were positive, which is significantly higher than ground glass opacity(GGO) dominant lesions(45.5%, 10/22, p=0.037). Figure 1



      Conclusion:
      Targeted NGS by OCP is feasible to detect multiple mutations simultaneously in early stage multiple primary lung cancers. Circulating tumor DNA has the ability to detect discordant somatic mutations and may represent of the overall mutational load and inter-tumor heterogeneity in multiple solid lung tumors.

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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-046 - Heterogeneity of NSCLC Surgery Exists in Treatment Patterns and Hospital Costs among Different Centers of China, a Study of 5060 Patients (ID 6344)

      14:30 - 14:30  |  Author(s): J. Wang

      • Abstract

      Background:
      Lung cancer is the leading cause of death of all tumors in China. But due to imbalanced development of different provinces, the surgical treatments of Non-small cell lung cancer in different areas of China diverse. The Chinese National NSCLC outcome registry was founded in 2013, which covers 17 provinces across China. We analyze the data of 5060 NSCLC patients retrieved from this registry to reveal the imbalanced circumstances.

      Methods:
      Data of stage I-III patients were obtained from the NSCLC surgical outcome registry, which included 5060 patients who underwent lung resection surgeries from 17 tertiary hospitals nationwide in 2013-2014. Baseline data , surgical treatment pattern parameters, pathology, number of lymph nodes dissected, and total hospital costs. Heterogenity of quantitative data was analyzed using Kruskal-Wallis test.

      Results:
      Among the 5060 patients, the mean age was 59.7 , while 3204 were male. Mean pre-op forced expiratory volume in 1 second (FEV1) was 2.23L(P<0.01), FEV1/FVC was 81.8%(P<0.01). 64.6% patients combined with at least one comorbidity. The average diameter of the tumor was 3.28cm(P<0.01). Mean operation time was 181.2 minutes. (P<0.05).The post-operative pathology confirmed 59.8% as adenocarcinoma while 30.2% as squamous carcinoma. Based on the data submitted by different centers, 88.4%(mean,0 to 98.41) patients who were confirmed as stage III patients received adjuvant therapy before surgery(P<0.01). The rate of minimally invasive surgery was 48.1(mean, 8.1 to 94.7)% in different regions(P<0.01). The number of stations of lymph nodes harvested was 5.8(mean, 4.3 to 7.4)(P<0.05). Mean hospital cost was 55070 (mean, 43051 to 69686 ) RMB(P<0.01).

      Center No. of lymph nodes in lobectomy Cost(CNY) VATS% Adjuvant therapy ofStage III% No. of patientssubmitted
      1 6.3 46861 90.2 99.3 838
      2 6.4 52891 27.5 98.8 788
      3 4.5 47516 59.0 84.8 729
      4 5.6 70875 60.3 50.3 676
      5 5.3 51742 78.9 98.6 392
      6 7.4 65409 26.1 100 387
      7 6.8 50696 8.5 100 293
      8 4.8 42206 8.3 98.6 265
      Total 5.9 57757 50.07 88.45 5060


      Conclusion:
      The heterogenity of surgical treatment is quite huge in different centers of China. The baseline status before surgery, pre-operative therapy strategy, surgical technique, and health economic data submitted to the registry showed imbalanced development of NSCLC surgical treatment in different regions of China.