Z Gastroenterol 2018; 56(10): 1237-1246
DOI: 10.1055/a-0661-6099
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Neuroendokrine Neoplasien im deutschen NET-Register

Neuroendocrine Neoplasia within the German NET Registry
Authors
, Im Namen aller Teilnehmer/innen am Deutschen NET-Registers,
Kollaboratoren:
Weitere Informationen

Publikationsverlauf

17. April 2018

13. Juli 2018

Publikationsdatum:
10. Oktober 2018 (online)

Zusammenfassung

Neuroendokrine Neoplasien (NEN) umfassen eine seltene Tumorentität mit heterogener Biologie, Prognose und therapeutischen Optionen. In Zusammenhang mit der kürzlichen Publikation der ersten deutschen Leitlinie zur Diagnostik und Therapie von NEN erfolgte die Analyse der Kohorte des Deutschen NET-Registers der Deutschen Gesellschaft für Endokrinologie (DGE). Hierzu wurden 2686 Fälle extrahiert und ihre Patientencharakteristika wie Alter, Geschlecht, Primärtumorlokalisation, Grading und Staging dargestellt sowie das Gesamtüberleben berechnet. Zusätzlich wurden die systemischen Behandlungsstrategien in den beiden größten Untergruppen, NEN des Dünndarms und Pankreas, im Stadium der Metastasierung analysiert.

Die Verteilung der Primärtumoren, die histopathologische Charakterisierung, das Tumorstadium sowie das Gesamtüberleben waren vergleichbar mit den Ergebnissen internationaler Registerstudien. Somatostatinanaloga (SSA) und die Peptid-Rezeptor-Radionuklid-Therapie (PRRT) waren die häufigsten systemischen Therapieverfahren bei Dünndarm-NEN. Hingegen wurde eine Chemotherapie – in Übereinstimmung mit der neuen Leitlinie – vor allem bei pankreatischen NEN eingesetzt und kam in der Erstlinie in ähnlicher Frequenz wie die SSA-Therapie bzw. in der Zweitlinie ähnlich häufig wie eine PRRT zum Einsatz. Prognostisch relevante Parameter waren die WHO-Klassifikation 2010 und das TNM-Staging.

Die aktuelle Analyse des deutschen NET-Registers charakterisiert damit eine multizentrische, interdisziplinäre, deutschlandweite Kohorte von NEN-Patienten und beschreibt die angewendeten systemischen Therapieverfahren, das Gesamtüberleben und die prognostische Bedeutung der WHO-Klassifikation 2010 sowie des TNM-Stadiums.

Abstract

Neuroendocrine neoplasias (NEN) comprise a rare tumor entity with heterogeneous biology, prognosis and therapeutic options. Together with the recent publication of the first German guidelines on diagnostics and therapy of NEN, an analysis of the German NET-registry cohort of the German Society of Endocrinology (DGE) was performed. For this purpose, 2686 cases were extracted and their patient characteristics (e. g., age, sex, histopathological characterization, grading and staging) were displayed and outcomes were calculated. Additionally, the systemic treatment reality in the two largest subgroups, small intestinal and pancreatic NEN, was analyzed within metastatic patients.

Distribution of primary tumor localization, histopathological classification, disease stage and overall survival was comparable with results from international registry studies. In concordance with current guidelines, somatostatin analogues (SSA) and peptide-receptor-radionuclide-therapy (PRRT) were the most common therapeutic modalities in small intestinal NEN. In pancreatic NEN, chemotherapy was used in first line as often as SSA. In second line, chemotherapy was used as often as PRRT. WHO-classification of 2010 and TNM staging proved to be of prognostic relevance.

The current analysis of the German NET-registry characterizes a multicentric, interdisciplinary cohort of NEN patients throughout Germany and it describes the applied systemic treatment modalities and overall outcome as well as the prognostic value of the WHO classification of 2010 and TNM staging.

 
  • Literatur

  • 1 Schimmack S, Svejda B, Lawrence B. et al. The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors. Langenbecks Arch Surg Dtsch Ges für Chir 2011; 396: 273-298
  • 2 Perren A, Couvelard A, Scoazec JY. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Pathology: Diagnosis and Prognostic Stratification. Neuroendocrinology 2017; 105: 196-200
  • 3 Panzuto F, Merola E, Pavel ME. et al. Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome. The Oncologist 2017; 22: 409-415
  • 4 Dasari A, Shen C, Halperin D. et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol 2017; 3: 1335-1342
  • 5 Quaedvlieg PF, Visser O, Lamers CB. et al. Epidemiology and survival in patients with carcinoid disease in The Netherlands. An epidemiological study with 2391 patients. Ann Oncol Off J Eur Soc Med Oncol ESMO 2001; 12: 1295-1300
  • 6 Lepage C, Bouvier AM, Phelip JM. et al. Incidence and management of malignant digestive endocrine tumours in a well defined French population. Gut 2004; 53: 549-553
  • 7 Williams ED, Sandler M. The classification of carcinoid tumours. Lancet 1963; 1: 238-239
  • 8 Bosman FT, Carneiro F, Hruban RH. WHO Classification of Tumours of the Digestive System. 4. Aufl. World Health Organization; 2010
  • 9 Garcia-Carbonero R, Rinke A, Valle JW. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy – Chemotherapy. Neuroendocrinology 2017; 105: 281-294
  • 10 Pavel M, Valle JW, Eriksson B. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Systemic Therapy – Biotherapy and Novel Targeted Agents. Neuroendocrinology 2017; 105: 266-280
  • 11 Rinke A, Wiedenmann B, Auernhammer C. et al. S2k-Leitlinie Neuroendokrine Tumore, AWMF-Reg. 021-27. Z Gastroenterol 2018; 56: 583-681
  • 12 Ploeckinger U, Kloeppel G, Wiedenmann B. et al. The German NET-registry: an audit on the diagnosis and therapy of neuroendocrine tumors. Neuroendocrinology 2009; 90: 349-363
  • 13 Lloyd RV, Osamura RY, Klöppel G. et al. IARC WHO Classification of Tumours of Endocrine Organs. Volume 10, 4th. Edition World Health Organization; 2017
  • 14 Garcia-Carbonero R, Capdevila J, Crespo-Herrero G. et al. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol Off J Eur Soc Med Oncol ESMO 2010; 21: 1794-1803
  • 15 Lombard-Bohas C, Mitry E, O’Toole D. et al. Thirteen-month registration of patients with gastroenteropancreatic endocrine tumours in France. Neuroendocrinology 2009; 89: 217-222
  • 16 Niederle MB, Hackl M, Kaserer K. et al. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer 2010; 17: 909-918
  • 17 Pape UF, Berndt U, Müller-Nordhorn J. et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2008; 15: 1083-1097
  • 18 Pape UF, Perren A, Niederle B. et al. ENETS Consensus Guidelines for the management of patients with neuroendocrine neoplasms from the jejuno-ileum and the appendix including goblet cell carcinomas. Neuroendocrinology 2012; 95: 135-156
  • 19 Pavel M, O’Toole D, Costa F. et al. ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site. Neuroendocrinology 2016; 103: 172-185
  • 20 Rinke A, Müller HH, Schade-Brittinger C. et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol Off J Am Soc Clin Oncol 2009; 27: 4656-463
  • 21 Caplin ME, Pavel M, Ćwikła JB. et al. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 2014; 371: 224-233
  • 22 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 Trial of177Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 2017; 376: 125-135
  • 23 Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med 1980; 303: 1189-1194
  • 24 Moertel CG, Lefkopoulo M, Lipsitz S. et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992; 326: 519-523
  • 25 Dilz LM, Denecke T, Steffen IG. et al. Streptozocin/5-fluorouracil chemotherapy is associated with durable response in patients with advanced pancreatic neuroendocrine tumours. Eur J Cancer 2015; 51: 1253-1262
  • 26 Krug S, Boch M, Daniel H. et al. Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms – Predictive and Prognostic Markers for Treatment Stratification. PLoS One 2015; 10: e0143822
  • 27 Strosberg JR, Fine RL, Choi J. et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 2011; 117: 268-2675
  • 28 Yao JC, Shah MH, Ito T. et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011; 364: 514-523
  • 29 Raymond E, Dahan L, Raoul JL. et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011; 364: 501-513
  • 30 2017-09-29-PR-EMA-Approval-Lutathera-ENG.pdf [Internet]. [zitiert 6. April 2018]. Verfügbar unter: https://www.adacap.com/wp-content/uploads/2017/09/2017-09-29-PR-EMA-Approval-Lutathera-ENG.pdf
  • 31 Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients – Full Text View – ClinicalTrials.gov [Internet]. [zitiert 12. April 2018]. Verfügbar unter: https://clinicaltrials.gov/ct2/show/NCT03049189
  • 32 Lepage C, Ciccolallo L, Angelis RD. et al. European disparities in malignant digestive endocrine tumours survival. Int J Cancer 2010; 126: 2928-2934
  • 33 Pape UF, Jann H, Müller-Nordhorn J. et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 2008; 113: 256-265
  • 34 Jann H, Roll S, Couvelard A. et al. Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome. Cancer 2011; 117: 3332-3341
  • 35 Rindi G, Falconi M, Klersy C. et al. TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst 2012; 104: 764-777
  • 36 Nathan H, Pawlik TM. Limitations of Claims and Registry Data in Surgical Oncology Research. Ann Surg Oncol 2008; 15: 415-423
  • 37 Thygesen LC, Ersbøll AK. When the entire population is the sample: strengths and limitations in register-based epidemiology. Eur J Epidemiol 2014; 29: 551-558