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Xiang-Peng Chu



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    FP01 - Early Stage/Localized Disease (ID 111)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP01.03 - Genetic Predisposition for Pre-Invasive Lung Adenocarcinoma Manifesting as Ground-Glass Nodules with Family History of Lung Cancer (ID 1512)

      00:00 - 00:00  |  Author(s): Xiang-Peng Chu

      • Abstract

      Introduction

      Lung cancer with family history have been increasing gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGN with lung cancer family history remains baffling.

      Methods

      This prospective study (NCT04220268) enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, which presenting as GGN in computer tomography (CT) scans. We used extreme phenotype approach to select 50 GGN patients with a family history of lung cancer (FHLC) in one or more first-degree relatives. Blood samples were collected and sequenced by whole exome sequencing (WES) to investigate rare but potential pathogenic germline mutations with a stepwise filtering strategy including: variant quality and classification, minor allele frequency (MAF) < 0.01 in public and local database, functional prediction and family segregation.

      Results

      In total, 2325 single nucleotide variants (SNVs) and 238 frameshift mutations with MAF <0.01 were finally identified through the filter. The number of these rare, damaging germline mutations in non-smoking patients were significantly higher than those in smoking patients (Spearman’s ρ= -0.33, p=0.02). Fifty-nine SNVs and 10 frameshifts were not only rare and deleterious but also presented in more than two families. Importantly, twenty of them had been reported to be associated with higher risk or carcinogenesis of lung cancer. Two of them were validated in 126 nonoverlapping susceptibility loci for lung carcinogenesis identified by genome-wide association studies (GWAS).

      Conclusion

      Patients with GGNs and FHLC may have inheritable carcinogenesis mutations. These variants may potentially contribute to the risk of pulmonary pre-invasive adenocarcinoma susceptibility in Chinese population. Non-smoking patients with GGN probably had higher genetic predisposition than the smoking patients.

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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): Xiang-Peng Chu

      • 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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    MA12 - Controversies Old and New (ID 230)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
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      MA12.10 - Treatment and Survival Differences in Patients with Large Cell Neuroendocrine Carcinoma of the Lung: A SEER Database Analysis (ID 3389)

      16:45 - 17:45  |  Author(s): Xiang-Peng Chu

      • Abstract

      Introduction

      Large cell neuroendocrine carcinoma of the lung (L-LCNEC) is a rare but highly aggressive tumor. We aimed to determine the differences in treatment and survival in L-LCNEC and to identify predictors for survival using Surveillance, Epidemiology, and End-Results (SEER) data.

      Methods

      Data of patients diagnosed with L-LCNEC in 2004–2015 were retrieved. Age, sex, race, and tumor site, size, grade, and stage were evaluated. Multivariable logistic and Cox regression were performed to identify factors associated with overall survival (OS) and cancer-specific survival (CSS).

      Results

      figure 1.jpgtable 1.jpg

      Figure 1. Effect of treatments in patients with large cell neuroendocrine carcinoma of the lung

      Table 1. Univariate and multivariate analyses of overall survival (OS) in the eligible patients.

      A total of 2,838 eligible cases were enrolled at the time of L-LCNEC diagnosis. In total, 1,774 (62.5%), 796 (28.0%), and 268 (9.5%) patients were diagnosed at the ages of 60-79, <60, and ≥80 years, respectively. L-LCNEC incidence (83.6%, N=2,373) was significantly high among Caucasians. Most tumors were in the right (56.2%, N=1,594) upper (53.5%, N=1519) lung lobe. Grade III (34.7%) and stage IV (49.0%) diseases were commonly detected in men (56.1%). Old age (60-79 years, hazard ratio [HR] [95% confidence interval]: 1.352 [1.136-1.609], P=0.001; ≥80 years, 1.841 [1.313-2.582], P<0.0001), stage III (2.053 [1.371-3.074], P<0.0001) and IV (3.878 [2.595-5.796], P<0.0001), and tumor size >5 cm(1.391[1.071-1.808], P=0.013) were independent unfavorable prognostic factors. Surgery (0.553 [0.397-0.770], P<0.0001) and chemotherapy (0.455 [0.392-0.528], P<0.001) were significant independent favorable prognostic factors. Patients treated with surgery, chemotherapy, or surgery plus chemotherapy had the lowest distant metastases rates.

      Conclusion

      We provide population-based estimates of the incidence and prognosis of L-LCNEC. Surgery and chemotherapy significantly improved the OS and CSS of patients with L-LCNEC.

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    P56 - Tumor Biology and Systems Biology - Basic and Translational Science - CT DNA (ID 193)

    • 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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      P56.01 - Postoperative ctDNA Positive Presents the High-risk of Recurrence in Resectable Non-Small Cell Lung Cancers (ID 1436)

      00:00 - 00:00  |  Author(s): Xiang-Peng Chu

      • Abstract

      Introduction

      Effective biomarkers to predict the prognosis for non-small cell lung cancer (NSCLC) patients after radical resection are needed. As a potential novel maker, ctDNA help to determine which patients harbor residual disease after surgery. Here, we analyze the significance of postoperative ctDNA in this prospective cohort.

      Methods

      Twenty-six NSCLC surgical patients were enrolled. The paired surgical tissues and postoperative peripheral blood samples were collected. Using hybridization capture-based NGS ER-seq method, 1021-gene panel for 26 tissues and 293-gene panel for 30 ctDNA samples, which enables simultaneously assess snv/indel, cnv and rearrangement variation.

      Results

      Median age was 61 years (range 33-78), 9 had smoking history, and 17 were males. There were 16 lung adenocarcinoma, 6 lung squamous carcinoma, 2 sarcomatoid carcinoma, 1 adenosquamous carcinoma and 1 lymphoepithelioma-like carcinoma. Four were stage Ⅰ, 10 stage Ⅱ and 12 stage Ⅲ. Thirteen patients received adjuvant therapy.

      In tissue samples, TP53 was the most common driver gene (65.4%). Followed by EGFR (30.8%), APC (19.2%), KRAS (11.5%), et. The median mutation number was 8.5 (from 3-50), and median TMB was 6.9muts/Mb (range 1-48). The mutation number had no relationship with ctDNA status. Postoperative ctDNA positive was found in 5 of 26 patients (19.2%), 3 stage Ⅲ and 2 stage Ⅱ, with a total of 10 mutations, range from 1 to 6 per-sample. The median highest mutant allele frequency (hMAF) per-sample was 0.1% (range 0.07%-6.6%). Two (7.7%) patients had actionable mutation in ctDNA.

      The median follow-up time was 10 months (range 3.5-18). Only 5 (5/21, 23.8%) patients in ctDNA negative group had disease recrruence, but patients in ctDNA positive group were all relapsed (P=0.004). The disease-free survival (DFS) was significantly shorter in ctDNA positive group than ctDNA negative (mDFS 7.4 vs 16.9 mos, P﹤0.0001; HR, 9.455; 95% CI, 1.149 to 77.78). Among 12 stage Ⅲ patents, shorter DFS was also observed in ctDNA positive patients than negative (P=0.0017; HR, 7.032).

      There were three patients had ctDNA monitoring results. Two persistently ctDNA negative cases did not relapse. But the patient with ctDNA changed from negative to positive relapsed within one month after transformation.

      Conclusion

      Postoperative ctDNA could be a promising biomarker to indicate the recurrence risk for NSCLC patients after radical surgery.