Response to Somatostatin Analog Therapy in a Patient With von Hippel-Lindau Disease and Multiple Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors (pNETs) are a feature of the inherited cancer syndrome von Hippel-Lindau (VHL) disease. An important management consideration in such patients, which differs from sporadic pNETs, is the potential for multifocal and metachronous disease. Repeated surgical interventions risk progressive parenchymal loss and consequent pancreatic endocrine and exocrine insufficiency; the risks of which must be weighed against the malignant potential of this poorly characterized pNET subgroup. Furthermore, the presence of other VHL-related tumors (eg, clear cell renal carcinoma, pheochromocytoma, and central nervous system hemangioblastomas) and previous collective family experience may impact on management strategy.
Surgical intervention is generally delayed until lesions exceed location-defined size criteria (≥3 cm body, ≥2 cm head), display a rapid growth rate (doubling time, <500 days), or there is evidence of locoregional disease,1 although these recommendations are based on limited retrospective data2 and have not been validated prospectively.
Somatostatin analogs (SSAs) are now an established treatment for advanced nonfunctioning enteropancreatic NETs and have been shown to increase progression-free survival,3 although an objective anatomical response is more rarely observed.4 Published evidence of the efficacy of SSAs in the context of pNETs in VHL is lacking. We report response to SSA therapy of multiple pNETs in a patient with VHL.
A 24-year-old woman with a known diagnosis of VHL (mutation in exon 3, R167W) was under routine surveillance. She had previously undergone staged bilateral adrenalectomies for pheochromocytomas and a distal pancreatectomy and splenectomy for a 35-mm grade 2 well-differentiated pNET. Her aunt had a metastatic and progressive pNET in the context of VHL.
During her postoperative imaging surveillance, 3 new pNETs developed within the tail, body, and uncinate process that grew on sequential examinations (maximum diameter, 16 mm; doubling time, 126 days). Chromogranin A and fasting gut peptides were not elevated. All the lesions were avid on Gallium DOTA-TATE imaging, confirming somatostatin receptor expression. Because of the lesion locations, there was a high risk of pancreatic insufficiency with further surgical resection. Given the rate of lesion growth, in combination with her family history of malignant disease and significant concerns about her ability to manage resultant pancreatic endocrine insufficiency, she underwent a trial of primary SSA therapy (lanreotide, Somatuline Autogel 90 mg monthly; Ipsen Limited, Slough, UK), which was well tolerated without adverse effects. After 6 months of treatment, reimaging demonstrated that all the pNETs had significantly reduced in size (largest diameter, 16–7 mm) and all met Response Evaluation Criteria in Solid Tumors criteria for partial response.5
This report documents the promising short-term radiological response to SSA therapy of multiple nonmetastatic nonfunctional pNETs in a patient with VHL. To our knowledge, this is the first published description of SSA use in this context. Although this initial observation requires confirmation in other patients and assessment of long-term response, it raises the possibility of SSA use as a strategy to delay the need for surgical intervention in VHL-related pNETs, thereby deferring, for a time at least, the associated risks of pancreatic insufficiency.