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

Susanna Majala; Hanna Seppänen; Jukka Kemppainen; Jari Sundström; Camilla Schalin-Jäntti; Risto Gullichsen; Jukka Schildt; Harri Mustonen; Tiina Vesterinen; Johanna Arola; Saila Kauhanen

doi:10.1186/s13550-019-0585-7

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

EJNMMI Res. 2019 Dec 23;9(1):116. doi: 10.1186/s13550-019-0585-7.

Authors

Susanna Majala^{1

2}, Hanna Seppänen³, Jukka Kemppainen^{2

4}, Jari Sundström⁵, Camilla Schalin-Jäntti⁶, Risto Gullichsen¹, Jukka Schildt⁷, Harri Mustonen⁸, Tiina Vesterinen^{9

10}, Johanna Arola⁹, Saila Kauhanen^{11

12}

Affiliations

¹ Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.
² Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.
³ Department of Abdominal Surgery, Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland.
⁴ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.
⁵ Department of Pathology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.
⁶ Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland.
⁷ Department of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital, Haartmaninkatu 4, FIN-00029, Helsinki, Finland.
⁸ Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland.
⁹ HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 400, FIN-00029, Helsinki, Finland.
¹⁰ Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, P.O. Box 20, FI-00014, Helsinki, Finland.
¹¹ Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland. saila.kauhanen@utu.fi.
¹² Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland. saila.kauhanen@utu.fi.

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.

Keywords: 18F-FDG-PET/CT; 68Ga-DOTANOC-PET/CT; Ki-67; NF-PNET; prospective study; surgical management.

Associated data

ClinicalTrials.gov/NCT02621541

Abstract

Associated data

Grants and funding