Chapter 147: Systemic and Regional Therapy for Pancreatic Neuroendocrine Tumors

INTRODUCTION

Pancreatic neuroendocrine tumors (PNETs) are thought to arise from mature endocrine cells in the pancreas and/or pleuripotent stem cells that have the capacity to differentiate into endocrine and exocrine cells.^1,2 Accumulating evidence also shows that PNETs are biologically and clinically distinct from other neuroendocrine tumors, NETs (i.e., carcinoids) and hence these tumor types should not be grouped together. The term carcinoid should also not be used to describe PNETs. PNETs comprise 1% to 3% of new pancreatic cancers but account for 10% of all prevalent pancreatic malignancies reflecting both the rarity of these tumors and also better prognosis as compared to pancreatic ductal adenocarcinoma.^3,4 An analysis of the Surveillance, Epidemiology, and End Results (SEER) database from 1973 through 2007 showed the relative rarity of all NETs, comprising approximately 0.9% of the database, with PNETs accounting for 7% of recorded primary sites within NETs. The reported incidence of PNETs in the United States is 1.8 in females and 2.6 in males per million, with most occurring in the fourth to sixth decades of life.⁵ However, with better awareness and advanced diagnostic tools, the incidence of PNETs has been rising. The natural history and principles of management of PNETs are discussed in detail in Chapter 145.

IMAGING FOR DIAGNOSIS AND STAGING OF PNET

Anatomic techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), with or without additional functional imaging such as somatostatin receptor scintigraphy (SRS; OctreoScan most commonly) positron emission tomography (PET) are used in staging of PNETs.

Helical multiphasic contrast-enhanced CT is recommended and has sensitivity of over 80%, although this may be diminished in tumors smaller than 2 cm.^6-8 NETs are highly vascular and typically enhance during the early arterial phase with washout during the portal venous phase (Fig. 147-1). MRIs reveal NETs as low intensity lesions on T1-weighted images and high signal intensity on T2-weighted images. MRI may detect more metastases than either CT or SRS scans with one study showing sensitivity rates of 95%, 79%, and 49% for each of these modalities, respectively.⁹

Endoscopic ultrasound provides the advantages of high-resolution imaging of the pancreas with an ability to detect very small subcentimeter lesions and can also provide tissue for histological diagnosis. In some studies, its sensitivity appears to be higher than that of CT, ranging from 80% to 90%, particularly for insulinomas.⁷ However, this procedure is highly dependent on the expertise of the endoscopist.

Most PNETs (except insulinomas) have high levels of somatostatin receptors subtypes 2 and 5, and can be imaged with a radiolabeled somatostatin analogue, typically 111-indium (¹¹¹In) pentetreotide (OctreoScan)^10...