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A. Mussi

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    MS05 - Modern Management of Neuroendocrine Tumours (ID 22)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Surgery
    • Presentations: 1
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      MS05.3 - Mediastinal Neuroendocrine Tumours (ID 478)

      14:00 - 15:30  |  Author(s): A. Mussi

      • Abstract
      • Presentation
      • Slides

      INTRODUCTION Mediastinal Neuroendocrine Tumors occur most frequently in the thymus. Primary Thymic Neuroendocrine Tumors (NETs) are rare and highly aggressive neoplasms; a little more than 350 cases have been described in the literature, many of which are single case reports. We collected one of the largest series ever reported through a multicenter International study, with the aim to evaluate factors influencing survival and recurrence development in patients with Thymic NETs. MATERIAL AND METHODS A multicenter retrospective study of patients operated for NETs between 1989 and 2012 in 9 high-volume International Thoracic Surgery Institutions, was conducted. According to the International Thymic Malignancy Interest Group (ITMIG) outcome measures, primary and secondary outcome were Cause Specific Survival (CSS) and Disease Free Survival (DFS). Competing-risks regression models (Fine and Gray method), taking into account death by any causes as competing event, were used to identify the association between individual factors and tumor related death. Cox proportional hazards regression models were used to define association between individual factors and DFS, considering R0 cases only. Univariate and multivariate analyses were also performed. RESULTS There were 52 patients (41 males –79%-, median age 49 years). The tumor was asymptomatic in 22 cases (42%). Endocrine paraneoplastic syndromes were observed in 23 cases (44%): 13 Cushing’s syndrome and 10 MEN-1 syndrome. Well differentiated neuroendocrine carcinoma (Typical and Atypical Carcinoid) was the commonest histological subtype (30 cases –58%-). Eight patients (15%) received induction therapy (3 chemotherapy, 2 chemo+radiotherapy, 2 biological therapy and 1 chemo+radio+biological therapy), because of their radiological invasiveness. Median sternotomy was the commonest surgical approach (29 cases). The median tumor size was 8 cm (range 1 – 31 cm); a complete resection (R0) was achieved in 48 cases (92%). Advanced Masaoka-Koga stage (III-IV) was observed in 35 patients (67%). Postoperative treatment was offered to 26 (50%): radiotherapy in 17, chemotherapy in 1, chemo+radiotherapy in 5 and chemo+radio+biological therapy in 3 patient, respectively. Three, 5 and 10-year survival rates were 89%, 76% and 51% (Figure 1). Recurrences were observed in 32 cases (62%): 11 local, 10 intrathoracic and 11 distant. Cumulative incidence of recurrence was 41% at 2 years and 70% at 3 years (Figure 2). Variables influencing survival were: tumor size (p< 0.00) and recurrences (p=0.01). Independents DFS predictors were: age > 50 (p= 0.02), paraneoplastic syndromes (p=0.02), symptoms at presentation (p= 0.01) and poor differentiated histology (p= 0.04). CONCLUSIONS We have confirmed that Thymic NETs are rare mediastinal tumors presenting with an aggressive biological behavior; surgery remains the mainstay of treatment and it should be proposed whenever possible, even in case of advanced diseases. Recurrences are frequent, especially in the first years after operation. Survival is statistically related to the tumor size and to the presence of recurrences, whereas, surprisingly, it is not influenced by induction/adjuvant treatment. A global International effort is needed to collect larger series and to confirm these conclusions. Figure 1: Thymic NETs overall survival curveFigure 1Figure 2: Thymic NETs: cumulative incidence of tumor recurrencesFigure 2

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-048 - An extensive analysis on T1aN0 non-small cell lung cancer: from surgery to pathology. (ID 2881)

      09:30 - 16:30  |  Author(s): A. Mussi

      • Abstract

      Unfortunately, non-small cell lung cancers are often diagnosed at an advanced stage. Early stage, and particularly T1aN0 NSCLCs, still represent a small percentage of all lung cancers at the moment of diagnosis. Research on early stage lung cancer may lead to discover new molecular insights which, hopefully, will reflect on new treatment opportunities: in particular, MicroRNAs (miRNAs) play a key role in cancer pathogenesis. We retrospectively reviewed our recent experience on surgically resected T1aN0 non small cell lung cancers, focusing on their surgical, histological, and molecular characteristic.

      From 2000 to 2010 we operated 114 T1aN0 non small cell lung cancers (81 male and 33 female). Most of them (90; 78,94%) underwent a lobectomy, 11 (9,65%) a segmental resection and in 13 cases (11,40%) a wedge resection; systematic lymphadenectomy was always performed. Operation was performed in 104 (91,23%) cases by thoracotomy (either posterolateral or lateral), 3 (2,63%) by VATS surgery and in 7 (6,14%) cases by robot assisted technique. All specimens were reviewed by two pathologists: 48 (42,10%) were invasive adenocarcinoma, 14 (12,28%) in situ/minimally invasive adenocarcinoma, 51 (44,74%) squamous cell carcinoma and 1 (0,88%) anaplastic carcinoma. Furthermore we evaluated Let-7g, miR-21 and miR-205 expression and their prognostic and predictive value.

      With a mean follow-up of 67 months, the 5-year overall survival is 75,00%. Recurrence occurred in 25 cases (21,93%), with a average disease-free interval of 26 months: 7 cases had a local recurrence, while 18 patients had distant metastasis. No correlation between survival, the kind of intervention performed, histology and cancer grading was found. Furthermore, maximum diameter of cancer do not affect survival. In average 8 ± 5,5 (range 3-28) lymphnodes were resected in 3 ± 1,3 stations (range 2-7): neither numbers of lymphnodes resected nor number of stations examined affect survival. All MicroRNAs considered were compared to the pathological and clinical variables.

      T1N0 non small cell lung cancer have a good survival with a low recurrence rate. In our experience histology, grading and the kind of resection (wedge resection and segmentectomy vs lobectomy) do not seem to influence recurrence rate and the prognosis. MicroRNAs tools have a good potential role as prognostic and predictive factors in lung cancer.