Skip to main content
Erschienen in: World Journal of Surgery 7/2019

19.02.2019 | Original Scientific Report

Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection

verfasst von: Maria Cattoni, Eric Vallières, Lisa M. Brown, Amir A. Sarkeshik, Stefano Margaritora, Alessandra Siciliani, Pier Luigi Filosso, Francesco Guerrera, Andrea Imperatori, Nicola Rotolo, Farhood Farjah, Grace Wandell, Kimberly Costas, Catherine Mann, Michal Hubka, Stephen Kaplan, Alexander S. Farivar, Ralph W. Aye, Brian E. Louie

Erschienen in: World Journal of Surgery | Ausgabe 7/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies.

Methods

We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage.

Results

Median follow-up was 47 (95%CI 41–79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3–70.9) and 47.4% (95%CI 32.3–61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01–1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6–93.6) and 38.2% (95%CI 20.6–55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1–78.8) and 54.2% (95%CI 32.6–71.6) (p = 0.31), respectively.

Conclusions

A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.
Literatur
1.
Zurück zum Zitat Fasano M, Della Corte CM, Papaccio F et al (2015) Pulmonary large-cell neuroendocrine carcinoma: from epidemiology to therapy. J Thorac Oncol 10:1133–1141CrossRefPubMedPubMedCentral Fasano M, Della Corte CM, Papaccio F et al (2015) Pulmonary large-cell neuroendocrine carcinoma: from epidemiology to therapy. J Thorac Oncol 10:1133–1141CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Veronesi G, Morandi U, Alloisio M et al (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53:111–115CrossRefPubMed Veronesi G, Morandi U, Alloisio M et al (2006) Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases. Lung Cancer 53:111–115CrossRefPubMed
4.
Zurück zum Zitat Roesel C, Terjung S, Weinreich G et al (2016) A single-institution analysis of the surgical management of pulmonary large cell neuroendocrine carcinomas. Ann Thorac Surg 101:1909–1914CrossRefPubMed Roesel C, Terjung S, Weinreich G et al (2016) A single-institution analysis of the surgical management of pulmonary large cell neuroendocrine carcinomas. Ann Thorac Surg 101:1909–1914CrossRefPubMed
5.
Zurück zum Zitat Filosso PL, Rena O, Guerrera F et al (2015) Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group. Eur J Cardiothorac Surg 48:55–64CrossRefPubMed Filosso PL, Rena O, Guerrera F et al (2015) Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group. Eur J Cardiothorac Surg 48:55–64CrossRefPubMed
6.
Zurück zum Zitat Sarkaria IS, Iyoda A, Roh MS et al (2011) Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg 92:1180–1186CrossRefPubMed Sarkaria IS, Iyoda A, Roh MS et al (2011) Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas: a single institution experience. Ann Thorac Surg 92:1180–1186CrossRefPubMed
7.
Zurück zum Zitat Asamura H, Kameya T, Matsuno Y et al (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24:70–76CrossRefPubMed Asamura H, Kameya T, Matsuno Y et al (2006) Neuroendocrine neoplasms of the lung: a prognostic spectrum. J Clin Oncol 24:70–76CrossRefPubMed
8.
Zurück zum Zitat Paci M, Cavazza A, Annessi V et al (2004) Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study. Ann Thorac Surg 77:1163–1167CrossRefPubMed Paci M, Cavazza A, Annessi V et al (2004) Large cell neuroendocrine carcinoma of the lung: a 10-year clinicopathologic retrospective study. Ann Thorac Surg 77:1163–1167CrossRefPubMed
9.
Zurück zum Zitat Takei H, Asamura H, Maeshima A et al (2002) Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 124:285–292CrossRefPubMed Takei H, Asamura H, Maeshima A et al (2002) Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 124:285–292CrossRefPubMed
10.
Zurück zum Zitat Eichhorn F, Dienemann H, Muley T et al (2015) Predictors of survival after operation among patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 99:983–989CrossRefPubMed Eichhorn F, Dienemann H, Muley T et al (2015) Predictors of survival after operation among patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 99:983–989CrossRefPubMed
11.
Zurück zum Zitat Fournel L, Falcoz PE, Alifano M et al (2013) Surgical management of pulmonary large cell neuroendocrine carcinomas: a 10-year experience. Eur J Cardiothorac Surg 43:111–114CrossRefPubMed Fournel L, Falcoz PE, Alifano M et al (2013) Surgical management of pulmonary large cell neuroendocrine carcinomas: a 10-year experience. Eur J Cardiothorac Surg 43:111–114CrossRefPubMed
12.
Zurück zum Zitat Iyoda A, Hiroshima K, Toyozaki T et al (2001) Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. Cancer 92:1108–1112CrossRefPubMed Iyoda A, Hiroshima K, Toyozaki T et al (2001) Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features. Cancer 92:1108–1112CrossRefPubMed
13.
Zurück zum Zitat Rossi G, Cavazza A, Marchioni A et al (2005) Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol 23:8774–8785CrossRefPubMed Rossi G, Cavazza A, Marchioni A et al (2005) Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung. J Clin Oncol 23:8774–8785CrossRefPubMed
14.
Zurück zum Zitat Dresler CM, Ritter JH, Patterson GA et al (1997) Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 63:180–185CrossRefPubMed Dresler CM, Ritter JH, Patterson GA et al (1997) Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung. Ann Thorac Surg 63:180–185CrossRefPubMed
15.
Zurück zum Zitat RieberJ SJ, Warth A et al (2015) Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas. Eur J Med Res 20:64–71CrossRef RieberJ SJ, Warth A et al (2015) Outcome and prognostic factors of multimodal therapy for pulmonary large-cell neuroendocrine carcinomas. Eur J Med Res 20:64–71CrossRef
16.
Zurück zum Zitat Kujtan L, Muthukumar V, Kennedy KF et al (2018) The role of systemic therapy in the management of stage i large cell neuroendocrine carcinoma of the lung. J Thorac Oncol 13:707–714CrossRefPubMed Kujtan L, Muthukumar V, Kennedy KF et al (2018) The role of systemic therapy in the management of stage i large cell neuroendocrine carcinoma of the lung. J Thorac Oncol 13:707–714CrossRefPubMed
18.
Zurück zum Zitat Filosso PL, Guerrera F, Evangelista A et al (2017) Adjuvant chemotherapy for large-cell neuroendocrine lung carcinoma: results from the European Society for Thoracic Surgeons Lung Neuroendocrine Tumours retrospective Database. Eur J Cardiothorac Surg 52:339–345PubMed Filosso PL, Guerrera F, Evangelista A et al (2017) Adjuvant chemotherapy for large-cell neuroendocrine lung carcinoma: results from the European Society for Thoracic Surgeons Lung Neuroendocrine Tumours retrospective Database. Eur J Cardiothorac Surg 52:339–345PubMed
19.
Zurück zum Zitat Kozuky T, Fujimoto N, Ueoka H et al (2005) Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol 131:147–151CrossRef Kozuky T, Fujimoto N, Ueoka H et al (2005) Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma. J Cancer Res Clin Oncol 131:147–151CrossRef
20.
Zurück zum Zitat Yamazaki S, Sekine I, Matsuno Y et al (2005) Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer 49:217–223CrossRefPubMed Yamazaki S, Sekine I, Matsuno Y et al (2005) Clinical responses of large cell neuroendocrine carcinoma of the lung to cisplatin-based chemotherapy. Lung Cancer 49:217–223CrossRefPubMed
21.
Zurück zum Zitat Ramirez RA, Chauhan A, Gimenez J et al (2017) Management of pulmonary neuroendocrine tumors. Rev Endocr Metab Disord 18:433–442CrossRefPubMed Ramirez RA, Chauhan A, Gimenez J et al (2017) Management of pulmonary neuroendocrine tumors. Rev Endocr Metab Disord 18:433–442CrossRefPubMed
22.
Zurück zum Zitat Mazières J, Daste G, Molinier L et al (2002) Large cell neuroendocrine carcinoma of the lung: pathological study and clinical outcome of 18 resected cases. Lung Cancer 37:287–292CrossRefPubMed Mazières J, Daste G, Molinier L et al (2002) Large cell neuroendocrine carcinoma of the lung: pathological study and clinical outcome of 18 resected cases. Lung Cancer 37:287–292CrossRefPubMed
23.
Zurück zum Zitat Saji H, Tsuboi M, Matsubayashi J et al (2010) Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy. Anticancer Drugs 21:89–93CrossRefPubMed Saji H, Tsuboi M, Matsubayashi J et al (2010) Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy. Anticancer Drugs 21:89–93CrossRefPubMed
24.
Zurück zum Zitat Battafarano RJ, Fernandez FG, Ritter J et al (2005) Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer. J Thorac Cardiovasc Surg 130:166–172CrossRefPubMed Battafarano RJ, Fernandez FG, Ritter J et al (2005) Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer. J Thorac Cardiovasc Surg 130:166–172CrossRefPubMed
25.
Zurück zum Zitat Zacharias J, Nicholson AG, Ladas GP et al (2003) Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection. Ann Thorac Surg 75:348–352CrossRefPubMed Zacharias J, Nicholson AG, Ladas GP et al (2003) Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection. Ann Thorac Surg 75:348–352CrossRefPubMed
26.
Zurück zum Zitat García-Yuste M, Matilla JM, Alvarez-Gago T et al (2000) Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR). Ann Thorac Surg 70:258–263CrossRefPubMed García-Yuste M, Matilla JM, Alvarez-Gago T et al (2000) Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study. Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR). Ann Thorac Surg 70:258–263CrossRefPubMed
Metadaten
Titel
Large Cell Neuroendocrine Tumor Size >3 cm Negatively Impacts Long-Term Outcomes After R0 Resection
verfasst von
Maria Cattoni
Eric Vallières
Lisa M. Brown
Amir A. Sarkeshik
Stefano Margaritora
Alessandra Siciliani
Pier Luigi Filosso
Francesco Guerrera
Andrea Imperatori
Nicola Rotolo
Farhood Farjah
Grace Wandell
Kimberly Costas
Catherine Mann
Michal Hubka
Stephen Kaplan
Alexander S. Farivar
Ralph W. Aye
Brian E. Louie
Publikationsdatum
19.02.2019
Verlag
Springer International Publishing
Erschienen in
World Journal of Surgery / Ausgabe 7/2019
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-019-04951-x

Weitere Artikel der Ausgabe 7/2019

World Journal of Surgery 7/2019 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.