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

Background: Predicting aggressive behavior of nonfunctional 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 the 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 ten 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.