Author of

• 10883

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  P1.14 - Poster Session 1 - Mesothelioma (ID 194)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10894

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    P1.14-012 - Activation of mTOR signal pathway is associated with prolonged survival in malignant pleural mesothelioma patients (ID 2715)

    09:30 - 16:30  |  Author(s): S. Hasegawa
    • Abstract

    Background
    Malignant Pleural Mesothelioma (MPM) is a rare disease with poor prognosis. The combination chemotherapy with cisplatin and pemetrexed is the first line of MPM. The AKT/mTOR (Mammalian Target of Rapamycin) pathways are known to be activated in some kind of cancer. The purpose of this study is to evaluate the correlation between the activation of these pathways and prognosis of MPM patients.

    Methods
    46 patients with MPM underwent a multimodality therapy including extrapleural pneumonectomy (EPP) at Hyogo College of Medicine, Nishinomiya, Japan from April 2004 to October 2012. The 46 cases included 35 males (76.0%) and 11 females (23.9%). Median Ages is 59.8 (ranged from 37 to 71 years). Histologic subtype is 42 epithelial type (91.3%), 2 biphasic type (4.3%), 1 desmoplastic type (2.1%), 1 small cell type (2.1%). Paraffin embedded surgical sample was used for immunohistochemistry to evaluate the expression of phospho- mTOR (p-mTOR) and phospho-S6 Ribosomal Protein (p-S6RP). Overall survival (OS) from the time of surgery was determined by Kaplan-Meier method and results were compared by log-rank test.

    Results
    OS was significantly better in phospho-S6RP positive patients (32/46) in comparative with phosphor-S6RP negative patients (14/46) (43.6 months vs. 14.4 months, P=0.03). OS was significantly better in phospho-mTOR positive patients (18/46) in comparative with phosphor-mTOR negative patients (28/46) (37.1 months vs. 14.4 months, P=0.08).

    Conclusion
    In MPM patients, high phospho-S6RP expression is predictive of improved OS. The assessment of phospho-S6RP expression is worth of prospective validation in future studies on a multimodality therapy of MPM. And this study support that the AKT/mTOR pathways is a promising candidate of molecular target therapy for MPM.

• 11826

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  P2.14 - Poster Session 2 - Mesothelioma (ID 196)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11831

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    P2.14-005 - Assessment of postoperative complications after the first all Japan multi-institutional trial of induction chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (ID 1517)

    09:30 - 16:30  |  Author(s): S. Hasegawa
    • Abstract

    Background
    The first all Japan multi-institutional trial was completed to evaluate the feasibility of induction chemotherapy using pemetrexed plus cisplatin, followed by extrapleural pneumonectomy (EPP) and postoperative hemithoracic radiation in patients with resectable malignant pleural mesothelioma (MPM). The main results were presented at the ASCO 2013. In this study, we especially reviewed major postoperative complications and mortality of patients who underwent EPP and determined the risk factors responsible for adverse outcomes.

    Methods
    From 2008 to 2010, 42 patients with MPM were enrolled in this study. Thirty-nine patients received planed chemotherapy. Thirty-three patients proceeded to EPP, which was completed in 30 patients. These patients were candidates in this study. Major complications were defined by grade 3, 4, 5 events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Treatment-related death was defined as any death occurring within 84 days after operation. Logistic regression analysis was performed on preoperative variables for major adverse outcomes.

    Results
    A total of 17 institutions in Japan with certified specialists in oncology, surgery and radiation therapy participated in this trial. Thirty patients (29 male, 1 female; median age of 66 years, range 43–74) completed EPP (14 right-sided and 16 left-sided), and macroscopic complete resection was accomplished in all patients. Histology of the tumors was epithelial in 22, biphasic in 4, sarcomatous in 1, and others in 3. Median operation time and blood loss were 437 minutes (range, 335-655) and 1461 gram (range, 390-4530), respectively. Major postoperative complications developed in 73.3% of the patients, and treatment-related death occurred in 4 patients (13.3%), which causes were cardiac herniation (n = 1), ARDS (n = 2), bronchial fistula and ARDS (n = 1). There were no significant predictors for major postoperative complications and treatment related death in both univariate and multivariate analysis.

    Conclusion
    We cannot find the predictor of major adverse events and treatment related death in MPM patients treated with induction chemotherapy followed by EPP. Although that is why sample size is small, we also recognize that multimodality treatment including EPP for MPM has more than 10% mortality and should be included in a prospective trial at specialized centers.

• 12441

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  P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12490

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    P3.06-050 - Characteristic Immunophenotype of Solid Subtype Component<br /> in Lung Adenocarcinoma (ID 3289)

    09:30 - 16:30  |  Author(s): S. Hasegawa
    • Abstract

    Background
    Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components.

    Methods
    We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results.

    Results
    Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P\\0.001, P\\0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor.

    Conclusion
    This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.