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F. Guerrera



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    MS 07 - Neuroendocrine Tumors other than SCLC: Pathology to Patient Management (ID 529)

    • Event: WCLC 2017
    • Type: Mini Symposium
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MS 07.05 - ESTS Registration for Neuroendocrine Tumors (ID 7673)

      15:45 - 17:30  |  Author(s): F. Guerrera

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Lung Neuroendocrine Tumors (NETs) are rare neoplasms derived from the neuroendocrine cells of the bronchopulmonary epithelium. They represent about 25% of all the neuroendocrine tumors, and no more than 2%-3% of all the primary tumors of the lung. Their incidence has recently increased by approximately 6% per year, probably due to the improved awareness as well as for the diffusion of lung cancer screening programs worldwide. NETs’ incidence now ranges from 0.2 to 2 per 100,000 individuals per year in the United States. Their rarity, along with the lack of randomized clinical trials, make lung NETs’ global management still questioned, especially in case of advanced diseases, and only few clinical recommendations currently exist. In 2012, during the Annual Meeting in Essen (Germany), the European Society for Thoracic Surgeons (ESTS) created a new Working Group (WG) specifically dedicated to the Lung NETs. The Steering Committees was composed by the following Thoracic Surgeons: Pier Luigi Filosso (Torino, Italy-Chair), Pascal Alexandre Thomas (Marseille, France), Mariano Garcia-Yuste (Valladolid, Spain), Eric Lim (London, UK), Federico Venuta (Rome, Italy), Alessandro Brunelli and Konstantinos Papagiannopoulos (Leeds, UK), Hisao Asamura (Tokyo, Japan). The aim of this WG was to create a group of physicians expert on Lung NETs in order to improve scientific knowledge on such rare neoplasms, and disseminate it among the scientific community. A specific database was rapidly designed, to retrospectively collect data of patients operated for lung NETs, and it was sent to all the ESTS Members who expressed their interest to this project. Moreover, a survey concerning lung NETs’clinical management was prepared and its results were recently published (Future Oncol. 2016;12:1985-1999). Up to now, 2040 operated NETs patients have been collected amongst 17 high-volume International Thoracic Surgery Institution worldwide. This retrospective database was used for several studies about lung NETs clinical behavior and outcome. In particular, the outcome and prognostic factors of two aggressive lung NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs) were the object of the first publication (Eur.J.Cardiothorac Surg. 2015;48:55-64). For ACs, age (P<0.001), tumour size (P=.015) and sub-lobar resections (P=0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumors (P=0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases were statistically more frequent in LCNCs (P=0.02), as expected. A prognostic model of survival for typical carcinoids (TCs) was the matter of the second publication (Eur.J.Cardiothorac Surg. 2015;48:441-447): an analysis of 1109 TC patients was performed. A prediction model for mortality, evaluating age, gender, previous malignancies, peripheral tumour location, TNM stage and ECOG PS was elaborated, and the final model showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap optimism-corrected 0.806). Moreover, this model has been recently validated by Cattoni and Coll. The treatment of biologically aggressive/advanced lung NETs was recently investigated in a paper published by the Journal of Thoracic Disease (J.Thorac. Dis. 2015;7:S163-S171). Surgery, whenever feasible, remains the mainstay of treatment, and chemo/radiotherapy should be reserved to progressive diseases. In case of resected N1-N2 carcinoids, a "watch and see" policy and a close clinical/radiological follow-up is also recommended. Surgery alone is not sufficient to treat high-grade NETs (e.g.: LCNC): adjuvant CT is suggested even in early stages. Platinum-Etoposide regimen demonstrated to be the most effective; Irinotecan and other biological drugs are also regarded to be very promising. The management of advanced lung NETs should be tailored by multidisciplinary teams including Medical and Radiation Oncologists, Surgeons, Pathologists, Pulmonologists, Endocrinologists, Interventional Radiologists; patients’ prognosis is mainly dependent on tumor grade and its anatomical extent. Large-cell neuroendocrine carcinoma (LCNC) is a rare tumor characterized by an aggressive biological behaviour and poor prognosis; its optimal treatment is still under debate. Some recent reports indicate that adjuvant chemotherapy (CT) may have a beneficial effect on survival. Data from 400 patients with resected LCNC were analyzed. The 3- and 5-year survival rates were 54.1% and 45%, respectively. With the multivariable model, increasing age, ECOG ≥2 and advanced TNM stage were indicators of poor prognosis. Weak evidence of a higher overall survival in patients receiving adjuvant CT (adjusted hazard ratio 0.73; 95% confidence interval: 0.56-0.96, P  = 0.022) was also observed (Eur.J.Cardio-Thorac.Surg. 2017;52:339-345). In Stage I TCs (SITCs) non-anatomical resections (wedge) are sometimes advocated because of their indolent behavior. An analysis on effect of surgical procedure on SITC patients’ survival was therefore done (Eur.J.Cardiothorac.Surg. 2017 submitted paper). Eight-hundred seventy-six SITC patients (569 females,65%) were included in this study; the 5-year OS rate was 94.3% (95%CI:92.2 –95.9). At univariable analysis, wedge resection resulted to be associated with a poor prognosis (5-year OS 82%,95%CI:0.71-0.89,P<.001) compared to other anatomical resections. At multivariable score-adjusted analysis, wedge resection confirmed to be an independent predictor of poor prognosis (HR2.17,95%CI: 1.19-3.96,P=.012). Since 2106, a lung NETs prospective database is active through the official ESTS European Database, and up to now, more than 150 new cases have been collected. Through this new platform, very easy to be used, we are confident to collect, in few years, more data especially on possible tumor recurrences and their treatment, as well as on the role of emerging biological drugs used in the adjuvant setting in advanced diseases. An active participation of Medical/Radiation Oncologists to this scientific project would be also desirable. The active role of the most important Scientific Societies could strongly support the success of this scientific project.

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