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M. Chen



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    MA 01 - SCLC: Research Perspectives (ID 650)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA 01.11 - Timing of Thoracic Radiotherapy Is More Important Than Dose Escalation in Patients with Limited-Stage Small Cell Lung Cancer (ID 7354)

      11:00 - 12:30  |  Author(s): M. Chen

      • Abstract
      • Presentation
      • Slides

      Background:
      The optimal thoracic radiation dose/fraction for limited-stage small cell lung cancer (SCLC) is still in debate. This study mainly aims to retrospectively compare the impact on local/regional progression-free survival (LRPFS) of different thoracic radiation dose/fraction schedules from two prospective trials.

      Method:
      Patients in the hyperfractionated arm received thoracic radiotherapy consisted of 1.5 Gy twice a day in 30 fractions to 45 Gy. Patients in the hypofractionated arm received 2.5 Gy daily in 22 fractions to 55 Gy. Kaplan-Meier method was used to estimate survival data. Multivariate prognosis analysis was made by Cox proportional hazard regression analysis.

      Result:
      Nighty-two and 96 patients were accrued into to the hyperfractionated and hypofractionated arm respectively. The 1-year, 2-year LRPFS rates of the two arms were 82.1%, 60.7% and 84.9%, 68.8% respectively (P=0.27). The median OS time (months) of the two arms were 28.3 and 22.0 respectively, while 1-year, 3-year, 5-year OS rates were 85.2%, 40.8%, 27.1% and 76.9%, 34.3%, 26.8% respectively (P=0.37). On multivariate Cox regression study, the time (days) from the initiation of chemotherapy to thoracic radiotherapy (TCT) ≤ 43 (HR: 0.397, 95%CI: 0.207-0.762, P=0.005) was independently associate with improved LRPFS. The time (days) from the start of chemotherapy to end of thoracic radiotherapy (SER) ≤ 63 (HR: 0.508, 95%CI: 0.322-0.762, P=0.044) and PCI (HR: 0.433, 95%CI: 0.298-0.630, P=0.000) were favorably related to OS. Grade 2 and 3 acute radiation esophagitis were observed in 28.3%, 8.7% and 15.5%, 2.1% of patients in hyper- and hypofractionated arm respectively (P=0.009). Figure 1



      Conclusion:
      Both hyperfractionated and hypofractionated radiotherapy had achieved good LRPFS and OS in this study, although there was no statistical significance between the two arms. Keep TCT ≤ 43, SER ≤ 63 resulted in better LRPFS and OS. However, the incidence of acute radiation induced esophagitis was significantly more common in the hyperfractionated arm than in hypofractionated arm.

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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-007 - A Real-World Study of Clinicopathological Characteristics and Survival Outcome in Advanced ALK-Positive Non-Small-Cell Lung Cancer (ID 8775)

      09:30 - 16:00  |  Author(s): M. Chen

      • Abstract

      Background:
      Crizotinib has resulted in substantial benefits for advanced non-small- cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. With limited real-world data available, the present work aimed to explore the clinicopathological characteristics and survival outcome of patients with advanced ALK+ NSCLC in a single center in China.

      Method:
      Data of 83 advanced ALK-rearranged NSCLC patients treated in Zhejiang Cancer Hospital were collected and analyzed retrospectively. Survivals were analyzed using the Kaplan-Meier method and were compared using the log-rank test. Multivariate analysis were performed by the Cox proportional hazard model.

      Result:
      Of the 83 patients enrolled, 33(39.8%) patients received crizotinib, and the other 50(60.2%) patients received chemotherapy as the initial treatment. The first-line use of crizotinib prolonged PFS compared with chemotherapy (median PFS 19.0 m vs. 5.7 m, P < 0.001), but not OS (46.0 m vs. 30.6 m, P=0.797). Till the last follow up, 71(85.5%) patients had received crizotinib, and 12(14.5%) patients were crizotinib-naïve. Patients who had received crizotinib had significantly longer OS than those who did not (48.9 m vs. 19.8 m, P < 0.05). Among the 71 patients who had received crizotinib,33(46.5%) used in first-line therapy, 22(31.0%) used in second-line therapy, and 16(22.5%) used after second-line therapy. There were not significant difference of OS among the three groups (30.6 m vs. 57.7 m vs. 40.8 m, P=0.583). The Cox multivariate analysis identified the following independent negative prognostic factors for OS: smoking (HR=4.725), liver metastasis(HR=4.570), bone metastasis (HR=2.651), and use of crizotinib (HR=0.295).

      Conclusion:
      Our real-world study showed that the use of crizotinib improved long-term survival of patients with advanced ALK-rearrangement NSCLC. There were no difference in survival outcome between patients with initial crizotinib and those with non-initial crizotinib.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.01-027 - TET2 Mutation as a Novel Mechanism of Acquired Resistance to EGFR TKIs Identified by a Mutational Profiling Using NGS (ID 9085)

      09:30 - 16:00  |  Author(s): M. Chen

      • Abstract

      Background:
      Overcoming acquired resistance to EGFR TKIs remains challenging, identification of actionable genetic alterations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. In our previous study, we performed mutational profiling in a cohort of 83 NSCLC patients using targeted next generation sequencing (NGS) and identified TET2 mutations in 12% of patients. This study aims to further explore the role of TET2 mutation in acquired EGFR-TKIs resistance in NSCLC cell lines with mutant EGFR.

      Method:
      CRISPR/Cas9 system was used to knock out TET2 gene in NSCLC cell line PC-9. Quantitative real-time PCR was performed to detect mRNA levels of TET2 gene, and western bot was performed to detect the expression levels of TET2 protein, thus cell line of TET2 silencing can be selected; positive for Annexin V and/or propidium iodide by flow cytometry was used to determine apoptotic rate. Bisulfite sequencing PCR (BSP) and real-time PCR for detection of EGFR promoter methylation status and mRNA expression.

      Result:
      By applying combined analyses of gene expression, apoptotic rate, and biochemical analyses of EGFR inhibitor responsiveness, we identified homozygous loss of TET2 to segregate EGFR-dependent cells. We show that in EGFR-dependent cells, TET2 loss partially uncouples mutant EGFR from downstream signaling and activates EGFR, thereby contributing to erlotinib resistance. Figure 1



      Conclusion:
      Our study is expected to provide new ideas and put forward corresponding relevant tactics for patients with secondary resistance to the first-generation EGFR TKIs.

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    P3.14 - Radiotherapy (ID 730)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P3.14-004 - Pathological Study on the Clinical Target Volume (CTV) in Limited-Stage SCLC for CT-Simulation Based Thoracic Radiotherapy Planning (ID 9722)

      09:30 - 16:00  |  Author(s): M. Chen

      • Abstract

      Background:
      The microscopic extension, known as clinical target volume (CTV), of the primary tumor in locally advanced non-small cell lung cancer for chest radiotherapy planning has been well studied. However, the CTV of the primary tumor in limited-stage small cell lung cancer (SCLC) for thoracic radiotherapy planning has not been reported. In this study, we tried to quantify CTV of primary tumor in limited-stage SCLC with pathological approach.

      Method:
      Patients with stage T1-2N0-1M0 small cell lung cancer, treated with two cycles of etoposide plus cisplatin neoadjuvant chemotherapy or without neoadjuvant therapy were eligible for this study. Routine radical lobectomy and mediastinal lymph node dissection were performed for these patients. After operation, the intact lung lobe specimens were perfused with 10% neutral formalin and inflated as the natural state in the body. Specimens should be fixed for at least 12 hours. The fixed specimens were sectioned at 3mm thickness along the cross-sectional position of the body, and for each slice, the gross tumor and its surrounding 2cm lung tissue was embedded with paraffin and sliced with 4μm thickness. HE routine staining and CD56 immunohistochemical staining were applied. The slides were scanned by KFBIO reading software, and the pathologists confirmed the microscopic extension of the surrounding tumor. The minimal distances between microscopic nidus and the edge of gross tumor were measured.

      Result:
      Eight patients were enrolled, of whom 4 received 2 cycles of neoadjuvant chemotherapy and 4 received surgery without any neoadjuvant therapy. In patients who received neoadjuvant chemotherapy, one was diagnosed as squamous cell carcinoma after surgery and was excluded for further evaluation of CTV, while 1 patient achieved pathologically complete remission of tumor.The median range of CTV in patients received or did not receive neoadjuvant chemotherapy were 0.4mm (0.05mm-2.76mm) and 1.7mm (0.08mm-12.7mm) respectively, a margin of 1.4mm and 10.2mm could cover 95% of microscopic nidus (P=0.00).

      Conclusion:
      The preliminary results of this study indicated that to take into account 95% of the microscopic nidus, a 1.4mm and a 10.2mm margin should be need for CT-simulation based thoracic radiotherapy planning for limited-stage SCLC patients who were treated with or without induction chemotherapy. However, the sample size of this study was small and more cases are needed to justify the results.