Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of neoplasms with a complex spectrum of clinical behavior. Although generally more indolent than carcinomas, once they progress beyond surgical resectability, they are essentially incurable. Systemic treatment options have substantially expanded in recent years for the management of advanced disease. Imaging plays a major role in new drug development, as it is the main tool used to objectively evaluate response to novel agents. However, current standard response criteria have proven suboptimal for the assessment of the antiproliferative effect of many targeted agents, particularly in the context of slow-growing tumors such as well-differentiated NETs. The aims of this article are to discuss the advantages and limitations of conventional radiological techniques and standard response assessment criteria and to review novel imaging modalities in development as well as alternative cancer- and therapy-specific criteria to assess drug efficacy in the field of GEP-NETs.

Keywords: Functional imaging; Neuroendocrine tumors; Radiological evaluation; Response assessment; Response criteria.

Fig. 1

Coronal reformatted arterial phase contrast-enhanced multidetector CT image demonstrates multiple enteropancreatic neuroendocrine tumors (arrows) in a patient with MEN-1. These tumors and their metastases are often hypervascular. They are usually more conspicuous in the early arterial acquisition phase

Fig. 2

SRS using ¹¹¹In-pentetreotide (a) and ¹⁸F-FDOPA PET/CT (b) performed 1 week apart in a patient with a well-differentiated metastatic ileal NET. Planar scintigraphy (a1) shows an uncertain liver lesion (red arrow), clearly located in segment II of the liver in the SPECT/CT fusion image (a2). Whole-body PET/CT image using ¹⁸F-FDOPA (b1 and b2) shows the same liver metastasis (red arrow) but also detects an additional liver lesion in segment V (yellow arrow). Follow-up ¹⁸F-FDOPA PET/CT (c1 and c2) performed after 12 cycles of octreotide therapy identifies multiple hepatic and peritoneal implants (both abdominal and subdiaphragmatic costophrenic angle) reflecting tumor progression

Fig. 3

SRPET using ⁶⁸Ga-DOTANOC in a patient with multiple liver metastases of a well-differentiated ileal NET. PET/CT scans performed before (left) and after 4 cycles of PRRT (¹⁷⁷Lu-DOTA-TATE) and subcutaneous monthly lanreotide (right) show a partial response to therapy (courtesy of Valentina Ambrosini and Stefano Fanti, S. Orsola-Malpighi University Hospital, Bologna, Italy)

Fig. 4

Perfusion CT images in a patient with NET liver metastases. Conventional CT image depicts a hypervascular liver metastasis in the left liver lobe (white arrows). Parametric maps of blood flow (BF), permeability (PS), and time to peak (TTP) show a different functional behavior at the periphery of the metastatic deposit (black arrows) compared to normal liver or the center of the metastasis, with increasing BF and PS and decreasing TTP. Perfusion CT provides additional information compared to morphologic imaging that may have prognostic value or be useful in tumor response evaluation

Fig. 5

Perfusion CT images in a patient with liver metastases from a neuroendocrine tumor pre- and posttherapy using antiangiogenic drugs. Parametric maps of blood flow and permeability superimposed over conventional CT images. Pretherapy study (a) demonstrated increased mean values of blood flow (115 mL/min/100 g) and permeability (51 mL/min/100 g), mainly at the periphery of the metastatic deposit. Posttherapy exam (b) evidenced a clear tumor response with drastic decrease of the values of both parameters (blood flow = 12 mL/min/100 g and permeability = 12 mL/min/100 g)

Fig. 6

Diffusion-weighted MRI (DW-MRI) of the pancreas. a Axial HASTE T2-weighted image does not depict any abnormality in the uncinate process of the pancreas. b DW image (left) at high b value (b = 1000 s/mm²) and fused image (right) superimposing axial T2-weighted MRI image and color-coded map derived from high b value (b = 1000 s/mm²) DW image clearly demonstrate a small pancreatic neuroendocrine tumor (arrows) with restricted diffusion at this level