Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT

Abstract

Background: Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging 68Ga-DOTANOC and 18F-FDG-PET/CT in patients with NF-PNETs. Methods: Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18F-FDG and 68Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or follow-up (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months. Results: Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a 68Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18F-FDG-positive tumor. In addition, one 68Ga-DOTANOC-negative patient was 18F-FDG-positive. 18F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. 68Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were 18F-FDG-positive. The 18F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18F-FDG-positive tumors were significantly larger than the 18F-FDG-negative tumors (P = 0.012). 18F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%. Conclusions: 18F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18F-FDG-avid NF-PNETs should be referred for surgery. The 68Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade. Trial registration: The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.