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Guangjian Yang



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    P1.11 - Screening and Early Detection (ID 177)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.11-12 - Genetic Landscape and Immune Microenvironment Features in Recurrence in Stage IA of Lung Adenocarcinoma (ID 2503)

      09:45 - 18:00  |  Author(s): Guangjian Yang

      • Abstract
      • Slides

      Background

      Lung adenocarcinoma (LUAD) leads to majority of lung cancer deaths. Various somatic mutations and copy number variations have been reported in LUAD, but their relevance to clinical prognosis of early stage LUAD is poorly understood. Besides, nearly 30% of patients with stage IA NSCLC eventually die of recurrence or metastasis in spite of the use of standard staging procedures. This study was designed to explore the genomic landscape in stage IA LUAD patients and find immune microenvironment features in recurrences.

      Method

      43 eligible stage IA LUAD patients with radical surgery and without adjuvant therapy from Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College were included in this study. Up to last follow-up in April 9th, 2018, 22 patients were relapsed and 21 were not recurrent. Clinical data were collected in the baseline data analysis. Whole-exome sequencing and RNA IO panel sequencing were performed in tumor and normal lung tissues.

      Result

      There were no significant differences in terms of clinical and pathological features comparing recurrences to non-recurrences. The most common mutated genes were TP53(48%), EGFR (18%) and KRAS (9%). Tumor mutation burden (TMB) values ranged from 0.2 to 16.4 Mutations/Mb, with a median of 2.5Mutations/Mb. Twenty-two differential genes were screened out and classified to five signatures in terms of its function. These five signatures including tumor cell proliferation, tumor antigen, cytotoxic T cells activity, T lymphocyte chemotactic factor, and natural killer cell activation were dramatically high expressed in non-recurrences (p<0.05). Besides, cytolytic activity was significantly higher in non-recurrences (p<0.05), which were represented as the log-average expression of GZMA and PRF1. Furthermore, six genes out of twenty-two genes were found to be significantly important in terms of disease-free survival (DFS) in stage IA LUAD with radical resection according to Kaplan-Meier analysis. However, there was no relation between TMB and DFS (p=0.501).

      Conclusion

      This is the first study reporting the relation of gene landscape and immune microenvironment features with prognosis in stage IA LUAD after curative resection. Host immunity is significantly related with the recurrence, whereas tumor mutation and TMB were not. Six genes related with host immunity have been found and promised to be novel prognostic factors in prognosis of stage IA LUAD.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-01 - Real World Treatment Outcomes in Chinese Patients with RET-Rearranged Lung Cancer (ID 2471)

      10:15 - 18:15  |  Author(s): Guangjian Yang

      • Abstract
      • Slides

      Background

      One global, multicenter study has identified available multi-targeted kinase inhibitors has limited activity in patients with RET-rearranged non-small-cell lung cancer (NSCLC). However, there is limited molecular and clinical data with RET-rearranged NSCLC in China.

      Method

      Retrospective real-world analysis of clinical, molecular, and treatment outcome of a web-based patient registry and hospital chart review in China.

      Result

      By 28/03/2019, 73 patients with RET-rearranged lung cancers from multiple hospitals in China were registered. The majority of patients were female (56.5%), never smokers (62.9%) with NSCLCs (98.4%). 15 different molecular subtypes of infusion partners were identified in which twelve subtypes were not reported before. KIF5B-RET was the most common (51.6%) followed by CCDC8-RET (25.8%). Two patients coexist with ALK fusion, one patient with EGFR mutation, and one patient with C-MET amplification. Median OS was 20.8m (95%CI 14.9-96.4) for 46 stage IV NSCLCs. Median PFS was 7.0m (95%CI 2.7-11.7) in patients who received 1st-line treatment including chemotherapy and multi-targeted kinase inhibitors. Patients with CNS (N=14, 30.4%) had significantly shorter PFS with those without CNS (N=32, 69.6%) (4.4m vs 9.1m; p=0.04, HR 2.343[1.040-5.279]). There was no statistically significant difference in PFS in terms of upstream fusion partners (KIF5B v other partner) (p=0.059). Besides, sixteen patients received one or more lines multi-targeted kinase inhibitors: cabozantinib (fourteen patients), vandetanib (two patients) and anlotinib (three patients). The median line of systemic therapy of the first RET TKI administered was as second line (range, first to third line). The median PFS of multi-targeted kinase inhibitor therapy in patients with CNS was 9.0m (95%CI 2.5-15.5m).

      Conclusion

      This is the first real-world study reporting clinical outcomes of Chinese RET-rearranged advanced NSCLC patients by now, which included the most samples, either. Most patients received chemotherapy with unfavorable survival, although several patients may benefit more from available multi-targeted kinase inhibitors. CNS is an important risk factor whereas upstream fusion partners are not. More and novel targeted therapies for RET-rearranged patients are urgently needed in China.

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    P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.16-06 - Molecular Features and Treatment Outcome of HER2 Mutated Advanced Non-Small Cell Lung Cancer Patients in China (ID 2826)

      10:15 - 18:15  |  Author(s): Guangjian Yang

      • Abstract
      • Slides

      Background

      HER2 mutations are found in 1-2% of lung adenocarcinoma patients. Chemotherapy remains the standard of care for patients harboring HER2 driver mutations, while many HER2 targeted tyrosine kinase inhibitors (TKIs) have been applied to them in practice in recent years. Studies comparing chemotherapy to HER2-TKIs was limited. This study was aimed to investigate molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer (NSCLC), and compare the different outcomes between chemotherapy and HER2-TKIs.

      Method

      Advanced or recurrent NSCLC patients with de novo HER2 mutations (N=75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web-based patient registry and hospital chart review.

      Result

      Between October 2012 and December 2018, 65 patients with in-frame insertion mutations, 8 with point mutations and 2 with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young-aged, females, never or light smokers, and adenocarcinoma. For HER2 mutated advanced NSCLC, chemotherapy achieved better outcomes than HER2-TKIs (median PFS: 5.5 vs 3.7 months in first line setting and 4.2 vs 2.0 months in second line setting, P=0.001 and 0.031, respectively). Especially for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2-TKIs both in first line (6.0 vs 2.6 months, P=0.008) and in second line (4.2 vs 2.6 months P<0.001).layout 1.jpglayout 2.jpg

      Conclusion

      Compared to existed HER2-TKIs, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype.

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