Virtual Library

Start Your Search

Changli Wang



Author of

  • +

    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
    • +

      JCSE01.17 - Weekly Nab-Paclitaxel Plus Carboplatin as Neoadjuvant Therapy for IIIA-N2 Lung Squamous Cell Carcinoma: A Prospective Phase II Study (ID 14706)

      11:15 - 11:15  |  Presenting Author(s): Changli Wang

      • Abstract
      • Slides

      Background
      To evaluate the safety and antitumor activity of weekly nab-paclitaxel combined with carboplatin in patients with advanced stage IIIA-N2 NSCLC patients with squamous histologyFrom April 2015 to August 2017, 36 treatment-naive, pathologically diagnosed IIIA-N2 lung squamous cell carcinoma patients were enrolled and given two cycles of weekly nab-paclitaxel (100mg/m2, day1,8,15 of a 21-day cycle) plus Carboplatin (AUC = 5 at day 1, q3w) as neoadjuvant therapy. Then resectability was assessed and surgery was performed for resectable lesions. Post-operative adjuvant chemotherapy regimens is the combination of Nab-paclitaxel (100mg/m2, qw x 6) and carboplatin (AUC 5, Q3W x 2) for patients with PD, adjuvant chemotherapy regimen will be changed. The primary objective is the safety and efficacy, and the secondary objectives are quality of life and the role of prognostic biomarker SPARC.

      Of 36 patients, 3 stopped treatment due to patient decision. 33 were finally evaluated and 1 is still on treatment. Significant tumor volume shrinkage was seen in some patients after the neoadjuvant therapy. 66.7% patients achieved partial response (PR), 21.2% patients achieved stable disease (SD). Disease control (PR +SD) rate was 87.9%. Finally, 23 patients underwent surgical resection, the respectability rate was 69.7%. 12.1% occurred disease progress and failed to achieve resection, including 3 with local progress and 1 with pulmonary metastatic nodule; Among 22 PR pts, 4 failed to achieve resection, in which 1 was due to heart function, the other 3 due to personal unwillingness. 2 of 7 with stable disease failed to achieve resection; the pathological improvement in T stage and N stage before and after treatment was 81.8% (18/22) and 50% (11/22) respectively. The major adverse event was neutropenia (grade I and II) and no serious AE was found.

      Nab-paclitaxel in combination with Carboplatin showed promising ORR rate and resection rate in of IIIA-N2 lung squamous cell carcinoma. The regimen could be a new chemo option as the neoadjuvant treatment. PFS and OS data will be reported after follow up completing.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
    • +

      MA21.05 - Comprehensive Genomic Characterization and Prognostic Nomogram Developed by 295-Gene Panel Targeted Sequencing (Now Available) (ID 13664)

      15:45 - 15:50  |  Author(s): Changli Wang

      • Abstract
      • Presentation
      • Slides

      Background

      The genomic landscape of lung cancer has been thoroughly studied in the western population. But comprehensive genetic profiling reports have been limited for the Chinese patients. Here we conducted deep targeted sequencing on a large cohort of Chinese treatment-naïve lung cancer patients and identified novel molecular patterns. We developed nomogram models for prognosis prediction by integrating genetic and clinical characteristics and aim to explore more precise models for risk stratification beyond TNM staging.

      Method

      This was a retrospective study, enrolling diagnosed lung cancer patients at Tianjin Medical University Cancer Institute & Hospital from 2009 to 2012. We developed genomic landscape by targeted sequencing using a panel consisting of exons and critical introns of 295 cancer-related genes. Nomogram models were established to provide risk stratification in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients

      Result

      513 tumor tissue samples were collected at very beginning of treatment (stage I, n=193; stage II, n=140; stage IIIA, n=140; stage IIIB, n=5; stage IV, n=28; unknown, n=7). The most frequently mutated oncogenic genes in LUAD were EGFR (55%) and KRAS (11%), compared to 14% and 33% in TCGA. Heterogeneity existed in terms of mutual exclusive and co-occurrent mutated gene pairs between LUAD and LUSC. In LUAD, pairs with most significant exclusivity was EGFR/KRAS and co-occurrent was NOTCH3/GRIN2A, whereas the most significant concurrent gene pair in LUSC was ZNF703/FGFR1. To predict survival, our nomograms identified that, in stage I-IIIA LUAD and LUSC, mutated TET2 contributed to more favorable DFS while mutations in EPHA3 and ETV5 indicated better OS. Stage and mutated KRAS were associated with inferior DFS and OS (DFS, n=222, c-index=0.714; OS, n=308, c-index=0.706). In the T1+2&N0&M0 subgroup, which is considered clinically low risk for relapse, older patients who carry BRCA2 mutations were found to strongly correlate with poor DFS (n=121, c-index=0.709), while age and mutated KRAS were distinct indicators of inferior OS (n=163, c-index=0.725). The calibration for survival probability displayed well agreement between nomogram prediction and actual outcomes. Stratification of different risk groups based on nomogram prediction displayed significant differences among Kaplan-Meier curves for survival outcomes (p<0.0001).

      Conclusion

      This is the so far largest cohort of Chinese lung cancer patients with comprehensive genomic profiling reported. We revealed unique molecular profiles than TCGA and distinct mutual exclusivity and co-occurrence patterns between LUAD and LUSC. In addition, the nomogram models show promise of more precise prognostic prediction of NSCLC patients when integrating genetic information with clinical characteristics.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.16-08 - Weekly Nab-Paclitaxel Plus Carboplatin as Neoadjuvant Therapy for IIIA-N2 Lung Squamous Cell Carcinoma: A Prospective Phase II Study (ID 12118)

      16:45 - 18:00  |  Presenting Author(s): Changli Wang

      • Abstract
      • Slides

      Background

      To evaluate the safety and antitumor activity of weekly nab-paclitaxel combined with carboplatin in patients with advanced stage IIIA-N2 NSCLC patients with squamous histology

      Method

      From April 2015 to August 2017, 36 treatment-naive, pathologically diagnosed IIIA-N2 lung squamous cell carcinoma patients were enrolled and given two cycles of weekly nab-paclitaxel (100mg/m2, day1,8,15 of a 21-day cycle) plus Carboplatin (AUC = 5 at day 1, q3w) as neoadjuvant therapy. Then resectability was assessed and surgery was performed for resectable lesions. Post-operative adjuvant chemotherapy regimens is the combination of Nab-paclitaxel (100mg/m2, qw x 6) and carboplatin (AUC 5, Q3W x 2) for patients with PD, adjuvant chemotherapy regimen will be changed. The primary objective is the safety and efficacy, and the secondary objectives are quality of life and the role of prognostic biomarker SPARC.

      Result

      Of 36 patients, 3 stopped treatment due to patient decision. 33 were finally evaluated and 1 is still on treatment. Significant tumor volume shrinkage was seen in some patients after the neoadjuvant therapy. 66.7% patients achieved partial response (PR), 21.2% patients achieved stable disease (SD). Disease control (PR +SD) rate was 87.9%. Finally, 23 patients underwent surgical resection, the respectability rate was 69.7%. 12.1% occurred disease progress and failed to achieve resection, including 3 with local progress and 1 with pulmonary metastatic nodule; Among 22 PR pts, 4 failed to achieve resection, in which 1 was due to heart function, the other 3 due to personal unwillingness. 2 of 7 with stable disease failed to achieve resection; the pathological improvement in T stage and N stage before and after treatment was 81.8% (18/22) and 50% (11/22) respectively. The major adverse event was neutropenia (grade I and II) and no serious AE was found.

      Conclusion

      Nab-paclitaxel in combination with Carboplatin showed promising ORR rate and resection rate in of IIIA-N2 lung squamous cell carcinoma. The regimen could be a new chemo option as the neoadjuvant treatment. PFS and OS data will be reported after follow up completing.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
    • +

      P3.03-10 - Transcriptomic Differences Between Early and Late Stage Lung Adenocarcinoma (Now Available) (ID 13656)

      12:00 - 13:30  |  Author(s): Changli Wang

      • Abstract
      • Slides

      Background

      Early and late stage lung adenocarcinoma patients differ significantly in overall survival. The tumor progression to advanced stage is driven by tumor genomic variation and the resulted abnormal gene expression profiles. A thorough study of molecular expression profiles between early and late stage lung adenocarcinoma will greatly contribute to the understanding of progression mechanism and biomarker discovery.

      Method

      We used RNA-seq to investigate the gene expression differences of 17 fresh frozen tissue samples, which were collected from 7 early (IA) and 10 late stage (IIIA, 3; IIIB, 2; IV, 5) lung adenocarcinoma patients.

      Result

      In total, 232 protein coding genes show differential expression levels between early and late stage subgroups. Gene functional annotations show that the differentially expressed (DE) protein coding genes are enriched in multiple KEGG pathways: pancreatic secretion, nicotine addiction, neuroactive ligand-receptor interaction, circadian entrainment, amphetamine addiction, and serotonergic synapse. The majority of pathway enriched DE genes (16 of 24) are translated into transmembrane proteins, such as ADCY2 (high in early) and GRIN2B (high in late) etc., with no correlation between expression level and certain stage. For cancer driver genes, ALK and NTRK2 show higher expression levels in late stage than in early stage. ERBB4 shows lower expression level in the late stage We also identified a group of keratin family genes (KRT2, KRT6A, KRT6B, KRT14, and KRT16) with higher expression levels in the late stage lung adenocarcinomas; Interestingly, keratin expression level distinguishes the subgroups of solid tumors in other cancer types. Though ERBB2, PIK3CA, and TP53 were not identified as differentially expressed genes, their expression variations in the late-stage samples are significantly larger than those in the early stagewhich could be a result of regulatory network change along the progression of tumor. Furthermore, 79 non-coding RNA were identified as DE “genes”. Among them, four previously studied ncRNA prognostic markers: MIR31HG, DRAIC, LUCAT1, and LINC00261 were also identified as DE “genes” with consistent expression-stage relationship comparing with the previous report. Two other ncRNA, VLDLR-AS1 and LINC01919, are highly expressed in early stage samples and may serve as potential prognostic markers for lung adenocarcinoma.

      Conclusion

      This study investigated the gene expression differences between early and late stage lung adenocarcinomas and identified differential expressed coding genes and non-coding genes, which will provide potential target information for the diagnosis and clinical intervention of lung adenocarcinoma patients.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

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

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
    • +

      P3.13-14 - Identification of Novel Mutations by High-Throughout Sequencing in T790M Wildtype/cMET Unamplified NSCLC with Acquired Resistance to EGFR TKIs (Now Available) (ID 12481)

      12:00 - 13:30  |  Author(s): Changli Wang

      • Abstract
      • Slides

      Background

      Lung cancer remains the leading cause of cancer-related death worldwide. Though most patients with EGFR activating mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), tumors will inevitably acquire resistance to first generation EGFR TKIs. EGFR T790M mutation and cMET amplification are common mechanisms. Further study is needed to explore unknown genomic alterations contributing to drug resistance.

      Method

      In the screening period of ASTRIS (D5160C00022) study of single center, tumor and blood samples from 69 stage ⅢB-Ⅳ NSCLC patients defined as acquired resistance to first generation EGFR TKIs (Gefitinib, Elortinib or Ecotinib) were collected. The cobas® and Droplet digital PCR (ddPCR) were used to detect T790M mutations in tumor samples and plasma ctDNA. cMET amplification were evaluated by Fluorescence in situ Hybridization (FISH). Exome sequencing were performed in four T790M wildtype/cMET unamplified samples.

      Result

      The T790M mutation rate of FFPE tissue cobas, plasma cobas and plasma ddPCR testing were 54.5%, 21.3% and 30.4% respectively. Taking all testing methods into account, the T790M positive rate was 52.2%. In 21 samples which tumor re-biopsy was performed, 14 were T790M positive (66.7%). cMET amplification were identified in 3 out of 7 T790M negative samples. Exome sequencing in 4 T790M wildtype/cMET unamplified samples and paired white blood cells identified a cohort of candidate key mutated genes including BRAF, FGFR1, PAK1, PCNT, PEBP4 and SOX3.

      Conclusion

      EGFR T790M mutation and cMET amplification are main mechanisms leading to EGFR TKI resistant in lung adenocarcinoma. These key mutated genes identified in the present study would need further functional study validation.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.