Abstract

Purpose: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. Patients and methods: Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52–66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. Results: Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1–8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). Conclusion: Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.

Highlights

  • Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of neoplasia, with a wide spectrum of clinical presentations and aggressiveness

  • All 83 patients underwent to 68Ga-DOTATOC PET and, in 68/83 patients, 18FFDG PET was performed

  • The availability of an accurate risk stratification assessment in patients affected by patients with PanNENs who are candidates to surgery is of utmost importance

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Summary

Introduction

Pancreatic neuroendocrine neoplasms (PanNENs) represent a heterogeneous group of neoplasia, with a wide spectrum of clinical presentations and aggressiveness. 2017 and WHO Classification of Tumours, Digestive System Tumours, 2019 [1,2] differentiate PanNENs with a well differentiated morphology (PanNETs: pancreatic neuroendocrine tumours) according to Ki67 proliferative index and mitotic count, which might have impact on patients’ survival [3]. Several imaging modalities are currently used to define morphological and functional features of PanNENs and to stage the disease [7]. Regarding morphological imaging, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are both essential to verify the resectability of the pancreatic lesion. These modalities are known to have limitations regarding the definition of pathological lymph nodes, which is based on the short axis diameter. In the field of molecular imaging, 68Ga-DOTA-peptides PET/CT seems to be the most accurate imaging modality to define somatostatin receptors (SSTR)

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