Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors

Tobias Krauss, Alfonso Massimiliano Ferrara, Thera P. Links, Ulrich Wellner, Irina Bancos, Andrey Kvachenyuk, Karina Villar Gómez De Las Heras, Marina Y. Yukina, Roman Petrov, Garrett Bullivant, Laura Von Duecker, Swati Jadhav, Ursula Ploeckinger, Staffan Welin, Camilla Schalin-Jäntti, Oliver Gimm, Marija Pfeifer, Joanne Ngeow, Kornelia Hasse-Lazar, Gabriela SansóXiaoping Qi, M. Umit Ugurlu, Rene E. Diaz, Nelson Wohllk, Mariola Peczkowska, Jens Aberle, Delmar M. Lourenço, Maria A.A. Pereira, Maria C.B.V. Fragoso, Ana O. Hoff, Madson Q. Almeida, Alice H.D. Violante, Ana R.P. Quidute, Zhewei Zhang, Mònica Recasens, Luis Robles Díaz, Tada Kunavisarut, Taweesak Wannachalee, Sirinart Sirinvaravong, Eric Jonasch, Simona Grozinsky-Glasberg, Merav Fraenkel, Dmitry Beltsevich, Viacheslav I. Egorov, Dirk Bausch, Matthias Schott, Nikolaus Tiling, Gianmaria Pennelli, Stefan Zschiedrich, Roland Därr, Juri Ruf, Timm Denecke, Karl Heinrich Link, Stefania Zovato, Ernst Von Dobschuetz, Svetlana Yaremchuk, Holger Amthauer, Ozer Makay, Attila Patocs, Martin K. Walz, Tobias B. Huber, Jochen Seufert, Per Hellman, Raymond H. Kim, Ekaterina Kuchinskaya, Francesca Schiavi, Angelica Malinoc, Nicole Reisch, Barbara Jarzab, Marta Barontini, Andrzej Januszewicz, Nalini Shah, William F. Young, Giuseppe Opocher, Charis Eng, Hartmut P.H. Neumann, Birke Bausch

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2cm; P<0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P=0.001). All metastatic tumors were ≥2.8cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8cm (94% vs 85% by 10 years; P=0.020; 80% vs 50% at 10 years; P=0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Original languageEnglish (US)
Pages (from-to)783-793
Number of pages11
JournalEndocrine-Related Cancer
Volume25
Issue number9
DOIs
StatePublished - Sep 2018

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Keywords

  • Management recommendations
  • PanNET
  • Survival
  • Von Hippel-Lindau disease

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Cite this

Krauss, T., Ferrara, A. M., Links, T. P., Wellner, U., Bancos, I., Kvachenyuk, A., De Las Heras, K. V. G., Yukina, M. Y., Petrov, R., Bullivant, G., Von Duecker, L., Jadhav, S., Ploeckinger, U., Welin, S., Schalin-Jäntti, C., Gimm, O., Pfeifer, M., Ngeow, J., Hasse-Lazar, K., ... Bausch, B. (2018). Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors. Endocrine-Related Cancer, 25(9), 783-793. https://doi.org/10.1530/ERC-18-0100