Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease

SIMPLE SUMMARY: Von Hippel–Lindau (VHL) is a hereditary syndrome associated with various tumors in the brain, spine, eyes, kidneys, adrenals, and in the pancreas. Approximately a fifth of patients with VHL develop tumors in the pancreas, and most of these tumors are localized and can be followed or resected in surgery. However, about a tenth of these patients develop metastatic disease which requires treatment with drugs. This review details the various medical interventions available for treating these patients. Such medications target the key factors that are overactive in tumor cells in the context of VHL. Many of them have been tested in clinical studies, and some have been approved recently for clinical use for localized pancreatic tumors in patients with VHL. To assist in managing patients with VHL and metastatic pancreatic tumors, we suggest an algorithm for choosing the optimal medical intervention for patients in this rare scenario. ABSTRACT: Von Hippel–Lindau (VHL) is a rare autosomal dominant hereditary cancer predisposition syndrome. Patients with VHL have a high risk for developing retinal and central nervous system hemangioblastoma, pheochromocytoma, renal cell carcinoma, and pancreatic neuroendocrine neoplasms (PNEN). About a fifth of patients with VHL will develop PNEN, and only a tenth of them will develop metastatic or unresectable (advanced) PNEN requiring medical intervention. In this review, we performed a literature search for studies, written in English, on the medical interventions for VHL-related localized and advanced PNENs and their clinical outcomes. We detail the various medical interventions for this rare group of patients, including their mode of action and potential efficacy and toxicity. Finally, based on the current literature, we delineate a possible management algorithm for patients with VHL and advanced PNEN. We can conclude that data on the efficacy of various vascular endothelial growth factor (VEGF) receptor inhibitors, and on the efficacy of belzutifan, a novel hypoxia-inducible factor 2 inhibitor, for the management of advanced PNEN in VHL, are scarce. Hence, deduction from the management of sporadic PNEN is required, and is implemented in the proposed management algorithm provided within this review.