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Wen-Fang Tang



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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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      JCSE01.22 - Differential Molecular Mechanisms Associated with Dramatic and Gradual Progression in NSCLC Patients with Intrathoracic Dissemination (ID 14713)

      11:15 - 11:15  |  Author(s): Wen-Fang Tang

      • Abstract
      • Slides

      Background
      Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development.We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters.We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors.NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTENmutations, as well as chromosome 18q loss are associated with rapid progression.

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    MA16 - Novel Mechanisms for Molecular Profiling (ID 917)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 203 BD
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      MA16.10 - Clinical Utility of Cerebrospinal Fluid Cell-Free DNA for Clarifying Genetic Features of Leptomeningeal Metastases in ALK Rearrangement NSCLC (Now Available) (ID 12142)

      14:35 - 14:40  |  Author(s): Wen-Fang Tang

      • Abstract
      • Presentation
      • Slides

      Background

      Leptomeningeal metastases (LM) were associated with a poor prognosis in non small cell lung cancer (NSCLC). LM were much more frequent in EGFR mutant patients, and cerebrospinal fluid (CSF) cell-free DNA (cfDNA) has shown unique genetic profiles of LM in patients harboring EGFR mutations in our previous studies. However, studies in ALK positive NSCLC patients with LM are scarce.

      Method

      Lung cancer patients with ALK rearrangement were screened from Sept 2011 to Feb 2018 at our institute. Leptomeningeal metastases were diagnosed by MRI or CSF cytology or next-generation sequencing (NGS) of CSF cfDNAs. Paired plasma were also tested by NGS.

      Result

      LM were diagnosed in 22 (7.6%) of 288 ALK rearrangement patients with lung cancer. A total of 11 ALK positive patients with LM were enrolled with CSF cfDNA tested by NGS (one case used CSF precipitates instead of CSF cfDNA). Paired plasma were available in 11 patients. Driver genes were detected in 75.0% CSF samples and 45.5% plasma respectively (P=0.214). Max allele fractions were higher in CSF cfDNA than in plasma (40.8% versus 0%, P=0.021). ALK variant 1 (E13:A20) was detected in 3 cases of CSF and paired plasma, respectively. ALK variant 2 (E20:A20) was identified in 5 cases of CSF and 1 paired plasma. Multiple copy number variants (CNV) were mainly found in CSF cfDNA, including EGFR copy number gains. Resistance mutations including gatekeeper gene ALK G1202R was identified in CSF cfDNA with ALK variant 1 and ALK G1269A was detected in plasma. The detection rate of TP53 was 45.4% versus 27.3% in CSF cfDNA and plasma.

      figures.jpg

      Conclusion

      CSF cfDNA was more sensitive than plasma to reveal genetic features of ALK-fusion LM, confirming its role as a liquid biopsy medium for LM in driver gene positive NSCLC.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • 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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      P2.01-18 - Differential Molecular Mechanisms Associated with Dramatic and Gradual Progression in NSCLC Patients with Intrathoracic Dissemination (ID 12979)

      16:45 - 18:00  |  Author(s): Wen-Fang Tang

      • Abstract
      • Slides

      Background

      Lung cancer is a highly heterogeneous disease with diverse clinical outcomes. The pleural cavity is a frequent metastasis site of proximal lung cancer. Better understanding of its underlining molecular mechanisms associated with dramatic and gradual progression of pleural metastasis in patients with non-small cell lung cancer (NSCLC) is essential for prognosis, intervention and new therapy development.

      Method

      We performed whole-exome sequencing (WES) of matched primary lung adenocarcinoma and pleural metastatic tumors from 26 lung cancer patients with dramatic progression (DP, n=13) or gradual progression (GP, n=13). Somatic alterations at both genome-wide level and gene level were detected. Kaplan-Meier survival analysis and multivariate Cox regression models were applied to analyze the association between different somatic alterations and clinical parameters.

      Result

      We first analyzed the differences in somatic alterations between AP and RP group in the primary tumors, and identified higher somatic copy number alteration (SCNA) level in DP group compared to GP group, which is significantly (p=0.016) associated with poorer progression-free survival (PFS). More specifically, patients with chromosome 18q loss in the primary tumor showed a trend (p=0.107) towards poorer PFS. PTEN (p=0.002) and GNAS (p=0.002) mutations are enriched in the primary tumors of DP group, and are associated with poorer PFS. Furthermore, pleural metastatic tumors harbor a relatively higher level of mutation burden (p=0.105) and significantly increased SCNA (p=0.035) compared to the primary tumors.

      Conclusion

      NSCLC patients in the attenuated progression group have more stable genomes. High level of genomic instability, GNAS and PTEN mutations, as well as chromosome 18q loss are associated with rapid progression.
      scna&survival.jpg

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • 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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      P2.16-47 - “Improved aBVA Method” and “Anterior VAB Method” Result in Analogous Survival Benefits During Right Upper Lobectomy (Now Available) (ID 14321)

      16:45 - 18:00  |  Author(s): Wen-Fang Tang

      • Abstract
      • Slides

      Background

      As concluded in recent research, compared with “Anterior VAB Method” (dissecting pulmonary vessels first, followed by the bronchus), “Improved aBVA Method” (dissecting the posterior ascending arterial branch first, followed by the bronchus and vessels) during RUL would promote surgical feasibility and postoperative recovery for lung cancer patients. This study compared their long-term survival benefits basing on propensity score matching (PSM).

      Method

      Consecutive lung cancer patients undergoing RUL were grouped into aBVA and VAB groups. PSM was conducted to reduce confounding bias between groups. After PSM, DFS and OS were estimated using the Kaplan–Meier method.

      Result

      1_副本.png

      397 patients were selected (167 in the aBVA group, and 230 in the VAB group). Before PSM, the histological subtypes, the mean number of dissected lymph node stations, operation time, amount of blood loss, number of used staplers, and the rate of conversion to thoracotomy during the operation, and the rate of pneumothorax and pneumonia, the mean duration of postoperative chest drainage after the operation were not balanced (P<0.05) between two groups. After PSM (caliper=0.02), 96 pairs of patients were successfully matched, and these 9 characters were all balanced (P>0.05) among the two groups. DFS and OS of the two groups were not significantly different (both P > 0.05). The median DFS and OS were comparable for all patients in the two groups (not arrived vs. 39 months, P > 0.05; both not arrived, P > 0.05). DFS and OS among patients with disease recurrence were not significantly different (both P > 0.05). The median DFS and OS were still similar in the two groups (16 vs. 11 months, P > 0.05; both not arrived, P > 0.05).

      Conclusion

      “aBVA Method” and “VAB Method” result in analogous survival benefits during RUL for lung cancer patients basing on PSM.

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