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I. Schmitt-Opitz



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    P2.04 - Poster Session with Presenters Present (ID 466)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
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      P2.04-029 - Primary Pulmonary Sarcoma: Risks and Optimal Surgical Treatment Options (Now Available) (ID 5652)

      I. Schmitt-Opitz

      • Abstract
      • Slides

      Background:
      Primary pulmonary sarcoma (PPS) is a rare tumor among malignant lung neoplasms. We aimed to clarify the clinical characteristics and therapeutic outcomes of patients who underwent surgical resection for PPS and to discuss beneficial treatment and surgical options.

      Methods:
      We retrospectively reviewed the records of those who underwent surgical resection for primary pulmonary sarcoma in our institution between 1995 and 2014. Cases only with biopsy were excluded.

      Results:
      Twenty four patients were analyzed. Eighteen were male. Their ages ranged from 18 to 83 years (mean 57). Surgical procedures were pneumonectomy in 10, lobectomy in 11 and wedge resection in 3. Complete resection was achieved in 14. Pathological stage based on the 7th lung cancer TNM classification were stage I in 4, II in 12, III in 2, and IV in 5. Four patients had metastasis in lymph nodes. The pathological grades were G1 in 4, G2 in 5 and G3 in 15. Five patients had postoperative complications. Tumor recurrence was observed in 5. During the observation 12 patients died. 5-year overall survival was 50.1%. Adverse prognostic factors for overall survival were detected as (p=0.001), incomplete resection (p=0.014), advanced pathological stage (p=0.001), higher pathological grade (p=0.028), and tumor size more than 7cm (p=0.044).

      Conclusion:
      Our series of primary pulmonary sarcoma revealed that pneumonectomy, incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long survival. Although complete resection is essential for primary pulmonary sarcoma due to its poor prognosis, it is recommended to avoid pneumonectomy, if possible, and to consider conservative surgical approaches including sleeve lobectomy.

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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-021 - When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All? (ID 5025)

      I. Schmitt-Opitz

      • Abstract

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer associated with exposure to asbestos. Untreated, MPM has a median survival time of 6 months, and most patients die within 24 months of diagnosis. Therefore an urgent need exists to identify new therapies for treating MPM patients. The potential for therapeutically targeting receptor tyrosine kinase (RTK) signalling networks is emerging as a critical mechanism in ‘oncogene addicted’ cancer, with RTK inhibitors evolving as areas of considerable importance in cancer therapy. Furthermore, RTK hetero-dimerization has emerged as a key element in the development of resistance to cancer therapy. As such TKIs which target several RTKs may have superior efficacy compared with TKIs targeting individual RTKs. We and others have identified c-MET, RON, Axl and Tyro3 as RTKs frequently overexpressed and activated in MPM, making these attractive candidate therapeutic targets. A number of orally bioavailable small molecule inhibitors have been developed which can target these receptors. LCRF0004 specifically targets RON, whereas ASLAN002 (BMS-777607) or Merestinib (LY2801653) are orally bioavailable small molecule inhibitors which inhibit c-MET, RON, Axl and Tyro3 at nanomolar concentrations. These drugs may therefore have applicability in the treatment/management of MPM.

      Methods:
      A panel of MPM and normal pleural cell lines were screened for expression of Tyro3, c-MET, RON and Axl by RT-PCR, and subsequently examined in a cohort of patient samples comprising benign, epithelial, biphasic, and sarcomatoid histologies by qPCR. The effects of two small molecule inhibitors LCRF0004, ASLAN002 on MPM cellular health were assessed in vitro. The effects of LCRF0004 and ASLAN002 were subsequently examined in an in vivo SQ xenograft tumour model.

      Results:
      Expression of various RON isoforms, c-MET, Tyro3 and Axl were observed in all cell lines. Significantly higher expression of all genes were found in the malignant tumour material versus benign pleura and this was validated in other datasets. Both LCRF0004 and ASLAN002 demonstrated significant anti-tumour efficacy in vitro. In xenograft models ASLAN002 was far superior to LCRF0004.

      Conclusion:
      Our results suggest that a multi-TKI, targeting the RON/MET/TAM signalling pathways, may be a more effective therapeutic strategy for the treatment of MPM as opposed to targeting RON alone.

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    WS04 - Mesothelioma Workshop (Ticketed Session) (ID 416)

    • Event: WCLC 2016
    • Type: Workshop
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 12/04/2016, 08:00 AM - 11:00 AM, Stolz 2
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      WS04.01 - Debate - Extrapleural Pneumonectomies Should be Performed for Pleural Mesothelioma (Now Available) (ID 6981)

      I. Schmitt-Opitz

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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