Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance

Abstract

Background: PET scans using FDG and somatostatin receptor imaging agents have both been used to study neuroendocrine tumours. Most reports have documented the sensitivity and specificity of each radiopharmaceutical independently, and even suggested the superiority of one over the other for different grades of disease. Aim: The aim of this work was to develop a grading scheme that describes the joint results of both the FDG and somatostatin receptor imaging PET scans in staging subjects with neuroendocrine tumours in a single combined parameter. The grading scheme that has been developed is referred to as the NETPET grade. Methods: This is a retrospective study which assessed subjects who had both FDG and somatostatin receptor PET imaging at our institution within 31 days of each other. The NETPET grade was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade and overall survival. Results: In the period 2011-2015 we were able to recruit 62 subjects with histologically proven metastatic neuroendocrine tumour for review. The NETPET grade incorporating both the FDG and somatostatin receptor imaging results was significantly correlated with overall survival by univariate analysis (p=0.0018), whereas in this cohort the WHO grade at the time of diagnosis did not correlate with survival. Conclusions: The NETPET grade has promise as a prognostic imaging biomarker in neuroendocrine tumours. It permits the capturing of the complexity of dual radiotracer imaging in a single parameter which describes the subjects' disease and is readily amenable to use in patient management and further research.

Keywords: Neuroendocrine tumour; PET scans.

Figure 1

The spectrum of results seen with SSRTI and FDG PET scanning in NETs, split into the categories that provided the basis for the NETPET grading scheme.

Figure 2

NETPET grading flowchart with selected example images shown.

Figure 3

An example of an SSTRI ([⁶⁸Ga]-DOTATATE) and FDG scan pair. The MIP (maximum intensity projections) images from the respective PET data sets are shown. The subject has SSTRI-dominant disease which exhibits some lesions with spatially concordant FDG uptake (closed arrows). While there are some sites of disease which are SSTRI-positive but FDG-negative (open arrows), importantly, there are no sites which are FDG-positive and SSTRI-negative. The example shown demonstrates a NETPET score of P3a, indicating that (i) the scans are positive on both SSTRI and FDG, and (ii) there were up to 2 lesions demonstrating approximately equivalent uptake between SSTRI and FDG, with the remaining lesions demonstrating greater SSTRI avidity than FDG.

Figure 4

Trial cohort selection

Figure 5

Kaplan-Meier curves for the NETPET subjects grouped as P1 (N=11), P2-P4 (N=33) and P5 (N=18).

Figure 6

Graphical representation of the concept behind the classification scheme

Figure 7

A 36 year old female was incidentally found to have obstructive liver function in a workup for an unrelated procedure. Computed tomography of the abdomen demonstrated a 20mm arterially enhancing mass in the tail of the pancreas and multiple enhancing bilobar hepatic lesions. Liver biopsy and subsequent pancreatectomy confirmed the presence of a grade 1 pancreatic neuroendocrine tumour (mitotic count<1, Ki-67 index =1%). Dual imaging at this point (7a, 7b) revealed the presence of SSTRI+ve/FDG-ve disease. Repeat imaging 20 months later (7c, 7d) demonstrated progressive disease and the new presence of FDG avidity. She underwent left hepatectomy for this lesion, with histology confirming the presence of a Grade 3 neuroendocrine tumour (mitotic count 20, Ki-67 index = 30%).