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Bo Yan



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.19 - ALTER-0303 Study: Tumor Mutation Index (TMI) For Clinical Response to Anlotinib in Advanced NSCLC Patients at 3rd Line (ID 14708)

      11:15 - 11:15  |  Author(s): Bo Yan

      • Abstract
      • Slides

      Background

      Anlotinib is an effective multi-targeted receptor tyrosin kinase inhibitor (TKI) for refractory advanced Non-Small Cell Lung Cancer (NSCLC) therapy at 3rd line. ALTER-0303 clinical trial has been revealed that Anlotinib significantly prolongs progression free survival (PFS; Anlotinib: 5.37 months vs Placebo: 1.40 months) and overall survival (OS; Anlotinib: 9.63 months vs Placebo: 6.30 months) with the objective response rate (ORR) of 9.18% and the disease control rate (DCR) of 80.95%. Here, we sought to understand the gene mutation determinants for clinical response to Anlotinib via next generation sequencing (NGS) upon cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) at baseline.

      Totally 437 advanced NSCLC patients enrolled in ALTER-0303 study, and 294 patients received Anlotinib therapy. Of the 294 patients, 80 patients were analyzed in the present study. Capture-based targeted ultradeep sequencing was performed to obtain germline and somatic mutations in cfDNA and ctDNA. Response analyses upon discovery cohort (n = 62) and validation cohort (n = 80) were performed by use of germline and somatic (G+S) mutation burden, somatic mutation burden, nonsynonymous mutation burden, and unfavorable mutation score (UMS), respectively. Based on the above independent biomarkers and their subtype factors, tumor mutation index (TMI) was developed, and then used for response analysis.

      Our data indicated that the patients harbouring less mutations are better response to Anlotinib therapy (G+S muatation burden, cutoff = 4000, Median PFS: 210 days vs 127 days, p = 0.0056; somatic mutation burden, cutoff = 800, Median PFS: 210 days vs 130 days; p = 0.0052; nonsynonymous mutation burden, cutoff = 50, Median PFS: 209 days vs 130 days; p = 0.0155; UMS, cutoff = 1, Median PFS: 210 days vs 131 days; p = 0.0016). TMI is an effective biomarker for Anlotinib responsive stratification (Median PFS: 210 days vs 126 days; p= 0.0008; AUC = 0.76, 95% CI: 0.62 to 0.89) upon discovery cohort and validation cohort (Median PFS: 210 days vs 127 days; p = 0.0006). Lastly, integrative analysis of TMI and IDH1 mutation suggested a more promising result for Anlotinib responsive stratification upon validation cohort (Median PFS: 244 days vs 87 days; p < 0.0001; AUC = 0.90, 95% CI: 0.82 to 0.97).This study provide a biomarker of TMI to stratify Anlotinib underlying responders, that may improve clinical outcome for Anlotinib therapy on refractory advanced NSCLC patients at 3rd line. Clinical trial information: NCT02388919.

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    MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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      MA01.01 - Proposal on Incorporating Lymphovascular Invasion as a T-Descriptor for Stage I Non-Small Cell Lung Cancer (Now Available) (ID 12754)

      10:30 - 10:35  |  Author(s): Bo Yan

      • Abstract
      • Presentation
      • Slides

      Background

      Lymphovascular invasion (LVI) and Visceral Pleural Invasion(VPI) have been reported to be risk factors for stage I Non-Small Cell Lung Cancer (NSCLC). However, only VPI was incorporated into the current 8th Tumor–Node–Metastasis(TNM) classification. This study aimed at exploring the prognostic impact of LVI on TNM staging in Pathological Stage I NSCLC.

      Method

      We retrospectively reviewed 2600 consecutive p-stage I NSCLC patients in the Shanghai Chest Hospital (2008-2012). By using the Kaplan–Meier method and Cox proportional hazard regression model, we identified the correlations between LVI, VPI and clinical outcomes in p-stage I NSCLC.

      Result

      Of all p-stage I NSCLC 2600 patients, 221 were pathologically diagnosed with LVI and 815 pathologically with VPI, respectively. It was observed that patients with LVI had an unfavorable lung cancer specific survival (LCSS) (hazard ratio [HR]: 1.883; 95% confidence interval [CI]: 1.351-2.625; P < 0.001) and recurrence-free survival (RFS) (HR: 2.025; 95% CI: 1.560-2.630; P < 0.001). The 5-year RFS rates of patients with LVI was significantly worse than those without LVI (61.2% VS 82.7%, P< 0.001). Patients with LVI exhibit similar prognosis (HR: 2.538; 95% CI: 1.570-4.098; P < 0.001) compared with that of VPI in pN0 non-small-cell lung cancer and a tumor diameter of 3cm or smaller. When tumor size was between 3-4cm, patients with LVI and VPI were associated with inferior prognosis than those with only LVI or VPI (P < 0.001).

      Conclusion

      The presence of LVI independently and significantly affects LCSS and RFS in patients with stage I NSCLC. Our results suggest that stage T1a-1c(IA) patients with LVI should be upstaged to T2a(IB), meanwhile, stage T2a(IB) patients coexist with LVI and VPI should be upstaged again in the TNM classification.

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