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A.G. Favaretto



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    MINI 24 - Epidemiology, Early Detection, Biology (ID 140)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI24.13 - Molecular and Pathological Features of Different Malignant Pleural Mesothelioma (MPM) Histologic Subtypes (ID 2121)

      16:45 - 18:15  |  Author(s): A.G. Favaretto

      • Abstract
      • Presentation
      • Slides

      Background:
      Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour, characterized by a higher resistance to systemic treatments, more frequent distant spread and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking

      Methods:
      The present study analyzed the expression levels of MDM2 and HIF1alpha and the presence of inflammation, necrosis and proliferation in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2, and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. A pathological assessment of necrosis, inflammation and proliferation index (through Ki67 immunostaining) was also performed. Molecular markers, pathological features and clinical characteristics were related to overall (OS) and progression free survival (PFS).

      Results:
      Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p<0.001), HIFalpha (p=0.013), necrosis (p=0.013) and proliferation index (p<0.001) were significantly associated with sarcomatoid/biphasic subtypes, while higher levels of inflammation were significantly associated with epithelioid subtype (p=0.044). MDM2 expression levels were correlated with HIF1alpha (p=0.0001), necrosis (p=0.008) and Ki67 (p=0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p=0.04), high levels of necrosis (p=0.037) and proliferation index (p=0.0002) with shorter PFS. This finding, however, was not confirmed by the multivariate analysis.

      Conclusion:
      Sarcomatoid/biphasic and epithelioid mesotheliomas show different MDM2 and HIF1alpha expression levels and are characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted in order to confirm a prognostic and predictive role of such markers and features.

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    P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Small Cell Lung Cancer
    • Presentations: 1
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      P2.07-011 - Maintenance with Lanreotide in SCLC Patients, Expressing Somatostatine Receptors, after Response to First Line Therapy (ID 2838)

      09:30 - 17:00  |  Author(s): A.G. Favaretto

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) is a rapidly progressive disease, characterized by rapid progression in spite of initial responsiveness to first-line chemotherapy. In this setting, an effective and safe maintenance therapy might result in improved disease control; to date, no maintenance strategy has been registered for SCLC yet. Since SCLC cells express a neuroendocrine phenotype, some tumors may express significant levels of somatostatin (SST) receptors; this feature might be exploited for new therapeutic approaches. The aim of our study is to investigate the activity of lanreotide, a SST analogue, as maintenance for patients with SCLC who have achieved a complete response (CR) or partial response (PR) to standard platinum-based chemotherapy (CHT) alone or combined with radiation therapy (RT) , in order to improve progression-free survival (PFS).

      Methods:
      In this prospective, open-label, multicenter, randomized phase III trial, patients with confirmed diagnosis of SCLC (limited or extended disease) expressing SST receptors (assessed by SST receptor scintigraphy) and with objective response (CR or PR) after CHT or CHT/RT are randomized (1:1) to one of the following arms: maintenance therapy/consolidation with 120 mg lanreotide, by deep subcutaneous injection, every 28 days up to progressive disease (PD) or one year (Arm A); or observation (Arm B). The patients were re-assessed every two months until documented PD during the first year after randomization, and then every three months. The planned enrollment period is 24 months, followed by a period of maintenance of 12 months and further 6 months for the completion of follow-up; the planned global period of the study is 3 years and a half.

      Results:
      This study is still ongoing; therefore, it is not possible to show its final results yet.. However, relevant preliminary data can be described. Currently, out of 76 expected patients, 53 were enrolled; of these, 11 patients (37.96%) in Arm A had limited disease and 18 (62.06%) extended disease. In Arm B, 11 patients had limited disease (45.83%) and 13 (54.17%) had extended disease. After one year of follow-up, among 29 patients randomized to Arm A, 1 patient died (3.45%), while 12 patients experienced PD (41.38%), and 16 are still on study (55.17%); among 24 patients randomized to Arm B, 2 deaths occurred (8.33%), while 11 patients experienced PD (45.83%) and 11 are still on study (45.83%). In Arm A, no significant adverse events were reported.

      Conclusion:
      This study will determine whether maintenance with lanreotide could prolong PFS of patients with SCLC expressing SST receptors and responsive to upfront CHT or CHT/RT. Moreover, the final results of this study might establish if this treatment could result in an improved overall survival rate after two years. To date, lanreotide has demonstrated an excellent safety profile in all the treated patients. On behalf of FONICAP (Forza Operativa Nazionale Interdisciplinare contro il Cancro del Polmone)

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