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Jie Qian



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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): Jie Qian

      • 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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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-29 - Crizotinib in Advanced Lung Adenocarcinoma Patients with ALK or ROS-1 Rearrangement: Is it the Same? (ID 12929)

      16:45 - 18:00  |  Author(s): Jie Qian

      • Abstract
      • Slides

      Background

      Crizotinib is an orally taken tyrosine kinase inhibitor (TKI) targeting both ALK and ROS1 rearrangement, which have defined two different molecular subgroup patients. The aim of the study was to compare the therapeutic efficacy of crizotinib in advanced lung adenocarcinoma patients diagnosed with ALK or ROS1 mutation.

      Method

      Patients diagnosed with ALK (Group A) or ROS1 (Group B) mutation were identified from our standardized registration system. The effectiveness of crizotinib in eligible patients was retrospectively analyzed.

      Result

      A total of 5348 and 4695 patients were screened and 393 (7.3%, 95% CI, 6.6%-8.0%) and 105 (2.2%, 95% CI, 1.8%-2.7%) positive patients were identified among the two groups, respectively. There were 141 and 32 eligible patients were included for survival analysis. The ORR is 53.0% (95% CI, 43.0%-63.0%) in group A, without statistical significance compared with group B (71%, 95% CI, 51.2%-90.4%, P=0.11). Similar result was also observed in terms of DCR (86%, [95% CI, 79.1%-92.9%] vs. 92.0%, [95%, CI, 80.0%-100.0%], P=0.74). The median PFS in group A was 12.4 months (95% CI, 10.2 -14.7 months), which was statistically worse than patients in group B (18.2 months, 95% CI, 6.3 -29.0 months, P=0.02). The OS was too immature to analyze.

      Conclusion

      Patients harboring ROS1 rearrangement derived better prognosis compared with these who had ALK rearrangement when treated with crizotinib.

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      P1.01-30 - Crizotinib in Advanced Non-Adenocarcinoma, NSCLC (NA-NSCLC) Patients with ALK Rearrangement: A Retrospective Study and Literature Review (ID 12942)

      16:45 - 18:00  |  Author(s): Jie Qian

      • Abstract
      • Slides

      Background

      The aim of the study was to investigate the prevalence of anaplastic lymphoma kinase (ALK) rearrangement in non-adenocarcinoma, non-small cell lung cancer (NA-NSCLC) patients and therapeutic efficacy of crizotinib in these patients.

      Method

      From January 2013 to January 2017, NA-NSCLC patients who were diagnosed with ALK rearrangement were screened. The effectiveness of crizotinib in positive patients was retrospectively analyzed. A literature review was performed and eligible cases were analyzed combined with our data.

      Result

      A total of 1212 NA-NSCLC patients were screened during the period with 25 positive patients identified (2.1%, 95% CI, 1.3%-2.9%). A statistically higher percentage of female patients (40.0% vs. 10.4%, P< 0.01), non-smoker (72.0% vs.43.2%, P< 0.01), containing adenocarcinoma component (36.0% vs. 7.1%, P< 0.01) and advanced stage (68.0% vs. 45.6%, P=0.03) were observed in ALK positive group. The median PFS of the 9 eligible patients in our institution was 7.0 months (95% CI, 0-15.6 months). We combined our data with the sporadic cases from 10 previous case reports (total n=19) and found that the median PFS was 7.0 months (95% CI, 5.6-8.4 months).

      Conclusion

      Our study suggested the opportunity to test ALK rearrangement in NA-NSCLC patients, especially in female, non-smoker and patients containing adenocarcinoma component. Crizotinib provides an option for the treatment of NA-NSCLC patients who diagnosed with ALK rearrangement.

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    P2.11 - Screening and Early Detection (Not CME Accredited Session) (ID 960)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.11-01 - Blood Transcriptomics Enables Detection of Pre-Invasive &amp; Minimally-Invasive Lung Adenocarcinoma (Now Available) (ID 12959)

      16:45 - 18:00  |  Author(s): Jie Qian

      • Abstract
      • Slides

      Background

      Although the low-dose computed tomography scan has been proved a useful tool for lung cancer screening, its highly false positive rate that usually over 90% limits its effectiveness for early detection of lung cancer. There is an urgent need to develop a non-invasive and cost-effective method to detect lung cancer at early stage.

      Method

      Peripheral blood samples were collected from patients pathologically diagnosed pre-invasive or minimally-invasive lung adenocarcinomas and healthy volunteers who reported with no any pulmonary disorders. Total mRNA from peripheral whole blood was processed according to PAXgene Blood RNA Kit protocol. In this study, we compared blood gene expression data from 95 samples using microarray analysis. Quantitative PCR was then used to validate biomarker candidates identified by differential expression analysis in microarray hybridization (N = 251). The gene panel finally selected was validated in an independent population (N = 54) using quantitative PCR. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve.

      Result

      The lung cancer-specific gene signatures were identified to construct predictive model based on 6-gene panel such as HSP90AA1, UQCRQ, NDUFB2, RPL24, CKLF and GLRX, which correctly classified 29 of 39 pre-invasive or minimally-invasive lung adenocarcinomas, 30 of 38 health controls with 76.6% accuracy in training set, and 7 of 8 lung cancer, 8 of 10 health controls with 83.3% accuracy in test set. Validation by quantitative PCR confirmed the Affymetrix microarray data, with 75.7% accuracy, 75.0% sensitivity, 76..6% specificity, 0.83 of area under curve (AUC) in training set, and 91.9% accuracy, 91.7% sensitivity, 92.3% specificity, 0.94 of AUC in test set. Independent validation testing confirmed these specific gene signatures did not derived from the result of random chance with 83.3% accuracy, 84.6% sensitivity and 79.3% specificity.

      Conclusion

      Our results indicated the feasibility of blood-based genetic signatures to identify pre-invasive and minimally-invasive lung adenocarcinoma as screening for lung cancer at very early stage.

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    P2.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 961)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.12-17 - Prophylactic Cranial Irradiation Can Not Provide Survival Benefits for Resected Small Cell Lung Cancer Without Lymph Node Involvement (ID 13996)

      16:45 - 18:00  |  Author(s): Jie Qian

      • Abstract

      Background

      Currently, prophylactic cranial irradiation (PCI) was recommended for all patients after resection small-cell lung cancers, even those without lymph node metastasis. However, there is no directly evidence supporting this recommendation. The purpose of the present study is to assess the role of PCI for this subset of patients.

      Method

      We retrospectively identified completely resected SCLC without lymph node involvement (N0M0) at the Shanghai Chest Hospital between January 2006 and May 2017.

      Result

      A total of 146 patients (44 patients received PCI, 102 patients did not) were identified in the study. During the observation period, 8.8 % (9/102) patients in the non-PCI-treated cohort and 11.4 % (5/44) patients in the PCI-treated cohort developed brain metastases. There was no significant difference in the risk of cerebral recurrence between the two cohorts with regard to the time to recurrence (P = 0.677). What is more, neither overall survival benefit (HR = 0.88, 95% CI: 0.47–1.65, P = 0.700) nor disease-free survival (HR = 0.95, 95% CI: 0.55–1.62, P = 0.835) was significant between the PCI-treated and non-PCI-treated cohorts.

      Conclusion

      The present study did not support using PCI in surgically resected small cell lung cancer without lymph node involvement. A relatively lower risk of brain metastasis in this particular subset might explain the inferior efficacy of PCI.

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    P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.15-22 - Optimal Glycemic Control Improves Prognosis for Lung Cancer Patients with Diabetes Mellitus (ID 14008)

      16:45 - 18:00  |  Author(s): Jie Qian

      • Abstract

      Background

      Diabetes mellitus (DM) is a common comorbidity in patients with lung cancer (LC). This study aimed to evaluate the prognostic value of DM comorbidity for LC patients with DM and to assess whether an optimal glycemic control improves survival.

      Method

      A total of 4390 patients diagnosed with LC between 2012 and 2013 at Shanghai Chest Hospital were retrospectively reviewed, 491 patients with DM and 3899 without DM. The relationship between hemoglobin A1c (HbA1c) level and the overal survival (OS) was plotted by a smooth curve. LC patients with DM were subdivided into the well-controlled group (HbA1c < 7%, n=438) and uncontrolled group (HbA1c ≥ 7%, n=53). OS differences among patients without DM, with well-controlled DM, and uncontrolled DM were evaluated by multivariate Cox regression analysis with adjustment for stage, sex, age, histology, smoking history and EGFR mutation status. The survival benefit of well-controlled DM was compared across subgroups.

      Result

      The median follow-up of the entire cohort was 35.8 months. DM patients (11.2%) had a significantly worse OS than nondiabetic patients [median (95% CI): 47.5 (39.0-56.1) vs. 73.6 (54.8-92.4) months, P<0.001]. The risk of mortality increased along with the elevation of HbA1c level. Uncontrolled DM patients tended to be male, elder, non-adenocarcinoma, with smoking history, wide-type EGFR mutations and advanced stage. Well-controlled DM patients had a worse OS [HR (95% CI): 2.3 (1.9-2.7), P<0.001] compared to nondiabetic patients without adjustment but a similar OS with adjustment for stage, sex, age, histology, smoking history and EGFR mutation status [HR (95% CI): 0.9 (0.8-1.1), P=0.185]. Benefit of well-controlled DM was more obviously seen in patients with advanced stage (III-IV) [HR (95% CI): 0.8 (0.6-1.1), P=0.130] or EGFR mutations [HR (95% CI): 1.2 (0.9-1.5), P=0.262].

      Conclusion

      Elevated glycemic status negatively affected OS for patients with LC. LC patients with DM is recommended to have a glycemic control (HbA1c < 7%) especially for those with advanced stage and EGFR mutations.

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.13-09 - ALTER-0303 Study: Tumor Mutation Index (TMI) For Clinical Response to Anlotinib in Advanced NSCLC Patients at 3rd Line (ID 12395)

      12:00 - 13:30  |  Author(s): Jie Qian

      • 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.

      Method

      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.

      Result

      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).

      Conclusion

      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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