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Si-Yang Liu



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    JICC01 - Joint IASLC-CAALC-CSCO Session: The Truth and Myth of Oral Anti-VEGFR Inhibitors for Advance NSCLC (ID 276)

    • Event: WCLC 2020
    • Type: Workshop
    • Track: N.A.
    • Presentations: 1
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      JICC01.13 - Discussant (ID 4270)

      07:00 - 09:00  |  Presenting Author(s): Si-Yang Liu

      • Abstract

      Abstract not provided

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    MA02 - Technological Advances in Diagnostics, Imaging and Therapeutics for Lung Cancer (ID 103)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Diagnostics and Interventional Pulmonology
    • Presentations: 1
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      MA02.08 - Computed Tomography Attenuation Value as Considerable Predictor for Malignancy in Clinical T1 Lung Adenocarcinoma (ID 1611)

      14:15 - 15:15  |  Author(s): Si-Yang Liu

      • Abstract

      Introduction

      To explore the quantitative variables of thoracic computed tomography for predicting the pathologic malignancy of cT1 lung adenocarcinoma.

      Methods

      We retrospectively collected data from 96 consecutive patients with clinical T1 lung adenocarcinoma. -160 Hu was used as the cutoff of solid and ground glass opacity portion. AAH, AIS, MIA and LPA were considered as less malignant (LM), while other subtypes of IACs were included into more malignant (MM) group.

      Results

      The area under receiver operating characteristic curves of m-CT value, D_solid, D_whole, Area_solid, Area_whole, 1D_CTR and 2D_CTR were respectively 0.89 (95%CI, 0.81 ~ 0.97; Se=83%, Sp=93%), 0.895 (95%CI, 0.832 ~ 0.958; Se=88%, Sp=79%), 0.736 (95%CI, 0.634 ~ 0.839; Se=87%, Sp=60%), 0.89(95%CI, 0.82 ~ 0.96; Se=87%, Sp=81%), 0.738 (95%CI, 0.634 ~ 0.841; Se=83%, Sp=63%), 0.861 (95%CI, 0.780 ~ 0.942; Se=90%, Sp=74%), 0.869 (95%CI, 0.788 ~ 0.949; Se=85%, Sp=84%). Multiple logistic regression revealed that mean CT value was the independent risk predictor of more pathologically malignancy of clinically T1 lung adenocarcinoma (p=0.003).

      Table1: Clinicopathological comparison between the less malignant and more malignant groups
        Less malignant(n=43) More malignant(n=53) p value
      Age, years, mean 56.12 65.38 <0.001
      Gender     >0.05
      Male 13 22  
      Female 30 31  
      Loaction     >0.05
      RUL 21 19  
      RML 3 3  
      RLL 7 12  
      LUL 7 10  
      LLL 5 9  
      D_solid(mm) 2.18 13.32 <0.001
      D_whole(mm) 16.84 23.13 <0.001
      Area_solid(mm²) 8.73 122.32 <0.001
      Area_whole(mm²) 187.44 322.56 <0.001
      1D_CTR 0.13 0.56 <0.001
      2D_CTR 0.07 0.35 <0.001
      2D m-CT Value(Hu) -629.40 -348.55 <0.001
      EGFR Mutation     >0.05
      Mutation 19 25  
      Wild type 18 25  
      ALK Mutation     >0.05
      Mutation 0 2  
      Wild type 30 43  
      D_solid: the longest diameter of the solid portion in the greatest horizontal section of nodule; D_whole: the longest diameter of the greatest horizontal section of nodule; Area_solid: the area of the solid portion in the greatest horizontal section of nodule; Area_whole: the area of the greatest horizontal section of nodule; 1D_CTR: D_solid/D_whole; 2D_CTR: Area_solid/Area_whole; m-CT value: mean CT attenuation value of the greatest horizontal section of nodule. mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit.
      Table2: Univariate and multivariate analysis for predicting the more pathologically malignant cT1 lung adenocarcinoma.
          Univariate analyses Multivariate analyses
        Category odd ratio 95% CI p value odd ratio 95% CI p value
      Age continuity 1.075 1.032~1.119 <0.001 1.019 0.955~1.088 0.56
      Gender Male vs Female 0.611 0.261~1.428 0.255      
      D_solid(mm) ≤3.473 vs > 3.473 29.593 9.624~90.996 <0.001 6.086 0.079~469.082 0.415
      D_whole(mm) ≤14.807 vs >14.807 10.05 3.686~27.402 <0.001 14.991 0.635~353.753 0.093
      Area_solid(mm²) ≤6.513 vs >6.513 28.75 9.517~86.850 <0.001 0.258 0.10~6.642 0.413
      Area_whole(mm²) ≤156.641 vs >156.641 8.25 3.201~21.265 <0.001 0.336 0.017~6.748 0.476
      1D_CTR ≤0.124 vs >0.124 27.927 8.862~88.011 <0.001 0.546 0.015~19.903 0.741
      2D_CTR ≤0.040 vs >0.040 25.143 8.526~74.148 <0.001 4.232 0.454~39.442 0.205
      m-CT Value(Hu) ≤-494.927 vs >494.927 65.185 16.481~257.815 <0.001 19.723 2.783~139.780 0.003
      95%CI: 95% confidential index; mm: millimeter; CTR: consolidation tumor ratio. Hu: Hounsfield unit.

      figue.jpg

      Conclusion

      Mean CT attenuation value is useful for predicting the higher pathologically malignant degree of clinical T1 lung adenocarcinoma. M-CT value is a potential reference factor for the formulation of surgical procedure for cT1 lung adenocarcinoma.

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    MA04 - Health Policy and the Real World (ID 217)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Health Services Research/Health Economics
    • Presentations: 1
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      MA04.06 - Clinical Characteristics and Outcomes in Advanced KRAS Mutant NSCLC – A Multi-Centre Collaboration in Asia (ATORG-005) (ID 3475)

      16:45 - 17:45  |  Author(s): Si-Yang Liu

      • Abstract

      Introduction

      KRAS driver mutations in advanced NSCLC have long been considered to be undruggable. However, promising efficacy data from early phase trials of novel therapies targeting KRAS have renewed focus on KRAS as an oncogenic driver. There is limited data on the prognostic and predictive significance of KRAS mutation subtypes. We present an interim analysis of a real world observational multi-centre study of advanced KRAS mutant NSCLC patients from five countries in Asia, conducted by the Asian Thoracic Oncology Research Group (ATORG).

      Methods

      Patients with advanced KRAS mutant NSCLC treated with at least one line of systemic therapy at tertiary centres in five Asian countries (China, India, Japan, Singapore, South Korea) between Jan 2014 and Dec 2018 were included. Baseline clinical characteristics, molecular profile and treatment outcomes were collected (median follow-up 35.5 months, 95%CI 28.7-50.3).

      Results

      A total of 155 patients were included in this interim analysis, with median age at advanced stage diagnosis 63 years (interquartile range [IQR] 56-70), 93% were ECOG 0-1, 70% were male and 64% were current or ex-smokers. In terms of ethnicity, 39% were Korean, 36% were Chinese, 15% were Japanese, 8% were Indian and 2% were Malay. Baseline histology was adenocarcinoma in 90%, squamous cell carcinoma in 4% and other histologies in 6%. KRAS mutation was detected by NGS in 141 (91%) patients, Sanger sequencing in 12 (8%) patients and RT-PCR in 2 (1%) patients. KRAS G12C (26%) was most common, followed by G12D (23%) and G12V (21%). The incidence of KRAS G12C mutation in patients with a smoking history was 35/99 (35%) compared with 6/56 (11%) in patients without any smoking history. Co-alterations were found with EGFR mutations (14%), ALK fusions (1%), ROS1 fusions (1%) and BRAF mutations (3%). PD-L1 TPS was 0% in 22%, 1-49% in 19%, ≥50% in 14% and unknown/not tested in 45%. Brain metastases were present at advanced stage diagnosis in 25% and lifetime prevalence was 35%. Patients received a median 2 lines of therapy. First-line systemic therapy consisted of chemotherapy alone (66%), targeted therapy (15%) or other therapies (19%). Median time to next treatment (TTNT) on first-line chemotherapy alone was 7.3 months (95%CI 5.0-9.5). Overall, the median TTNT for first-line and second-line therapy was 7.7 (95%CI 6.5–10.0) and 7.0 (95%CI 5.3–10.9) months, respectively. 63% of patients had died, and 37% of patients were still alive or lost to follow-up at the time of data cut-off. Median OS for the overall cohort was 21.6 months (95%CI 15.9-27.6). Median OS was greater in immunotherapy treated (alone or in combination at any line; 45%) versus non-immunotherapy treated (55%) patients (27.6 [95%CI 19.1-37.9] months versus 15.4 [95%CI 10.3-23.7] months, HR 1.8, 95%CI 1.2-2.7, logrank p=0.005).

      Conclusion

      In Asian KRAS mutant NSCLC, duration of first-line therapy and survival outcomes remain poor – emphasising the need for greater therapeutic options for patients with a KRAS driver mutation. Additional sites/countries are planned and recruitment to this study is ongoing.

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    P72 - Tumor Biology and Systems Biology - Basic and Translational Science - Tumor Microenvironment (ID 211)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P72.02 - Cellular Landscape of Tumor Immune Microenvironment and Genetic Signatures Identify Prognostic of LUAD (ID 736)

      00:00 - 00:00  |  Presenting Author(s): Si-Yang Liu

      • Abstract
      • Slides

      Introduction

      Tumour microenvironment (TME) has been recognized to support the initiation and progression of lung adenocarcinoma (LUAD). The innate and adaptive immune cells in the lung TME harbour both tumour-promoting and tumour-suppressing activities, which may also predict clinical outcome. Therefore we carried out a systematic analysis of cellular interactions in tumor immune microenvironment. And identify cell-intrinsic and cell-extrinsic pathways cell types and activation states that may serve as biomarkers of overall survival (OS).

      Methods

      Public gene-expression data and relevant clinical annotation were obtained from Gene-Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Three TME infiltration patterns were comprehensively analyzed in 442 LUAD patients using CIBERSORT algorithm and the LM22 gene signature. Based on the TME patterns, we build a model to calculate TMEscore based on gene set variation analysis via ssGSEA algorithm. Functional enrichment analysis were performed by GO and KEGG.

      Results

      Four datasets with available outcome data and clinical information in GEO and TCGA-LUAD were enrolled in our study. GSE72094 was used as the training cohort, while GSE11969, GSE26939, GSE31210 and TCGA-LUAD was used as validation cohorts. TME cell network established based on GSE72094 depicted a comprehensive landscape of tumor-immune cell interactions, cell lineages, and their correlation with OS (Fig. 1A, 1B). Three subgroups with distinct TME signature gene sets were obtained/identified based on unsupervised hierarchical clustering in 442 LUAD cases. OS in TME gene subgroup B was significantly longer than which in TME gene subgroup A and subgroup C. TME gene group B was associated immune activation (Fig. 1C). TMEscore was further constructed using principal component analysis algorithms. Lower TMEscore is significantly associated with better prognosis. Functional annotation analysis showed TMEscore had a positive correlation with cell cycle, DNA replication, homologous recombination, mismatch repair, nucleotide excision repair and DNA damage repair (Fig. 1D). The enriched pathways in subtype with lowest/low TMEscore involved bile_acid_metabolism, fatty_acid_metabolism and myogenesis. While high TMEscore subtype was characterized by significant enrichment of interferon_alpha_response, myc_targets and unfolded_protein_response pathway (Fig. 1E). TMEscore model was then validated on 525 patients from GEO datasets and 585 patients from TCGA-LUAD project and proved to be a valuable method for prognostic stratification of LUAD except for TNM stage(Fig. 1F).

      fig-1.png

      Conclusion

      Variability in the composition of the tumor immune microenvironment contributes to heterogeneity in OS. Deeper validation is in need to define the positive association between lower TMEscore and longer OS.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.60 - FLAIR: Phase II Study of Osimertinib plus Bevacizumab versus Osimertinib in Advanced NSCLC Patients with EGFR L858R Mutation (ID 3221)

      00:00 - 00:00  |  Author(s): Si-Yang Liu

      • Abstract
      • Slides

      Introduction

      The 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib monotherapy has been considered as the new standard of care for advanced EGFR mutated non-small-cell lung cancer (NSCLC) patients. However patients with L858R mutation have achieved lower efficacy of EGFR-TKIs than those with 19Del mutation, even with osimertinib. Herein to improve the efficacy of L858R population is still unmet medical needs. While CTONG1509 study has presented the addition of bevacizumab to 1st generation EGFR TKI erlotinib appears to significantly improve L858R patients’ progression free survival the combination of osimertinib and bevacizumab is worth deep exploration.

      Here we present the rationale and study design for the FLAIR trial, a multicenter, open label, randomized, phase II study.

      Methods

      Study entry will be limited to adults aged ≥ 18 years with primary recurrent or metastatic nonsquamous non-small-cell lung cancer with documented an EGFR exon 21 L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until disease progression or unacceptable toxicity.

      The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of overall response (DoR), time to treatment failure (TTF), overall survival rate at 2 years, and safety and tolerability.

      In the HR assumption of 0.65, sample size of 90 patients is driven by the needs of 67% statistic power for the test at the significance level of 0.2, two sided, with the accrual period of 8 months and the longest follow-up of 32 months.

      The first analysis (primary analysis) data cut-off (DCO) point will be happened when 70% data maturity for PFS based on investigator assessment (according to RECIST 1.1) has been reached (depending on the actual event rate).

      o+t.jpg

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