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 68 Ga-DOTANOC and 18 F-FDG-PET/CT in patients with NF-PNETs. Methods: Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18 F-FDG and 68 Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or followup (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 68 Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18 F-FDG-positive tumor. In addition, one 68 Ga-DOTANOC-negative patient was 18 F-FDG-positive. 18 F-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. 68 Ga-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 18 F-FDG-positive. The 18 F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18 F-FDG-positive tumors were significantly larger than the 18 F-FDG-negative tumors (P = 0.012). 18 F-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: 18 F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18 F-FDGavid NF-PNETs should be referred for surgery. The 68 Ga-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.

Nordic guidelines 2021 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

“…Other types of positron emission tomography (PET) 18 FDG-PET and SRI provide complementary information regarding the different biological characteristics of the lesions. Prognosis is generally worse if a tumour is 18 FDG positive and SRI negative and vice versa [17][18][19]. 18 FDG-PET should be performed in localised NET G3 as well as in NECs and may be valuable in G1-2 NETs for prognostication and therapy planning.…”

Somatostatin Receptor PET/CT Imaging for the Detection and Staging of Pancreatic NET: A Systematic Review and Meta-Analysis

“…However, only the study by Ilhan et al [ 39 ] specifically addressed this point in a study cohort of pNET patients, in which imaging results altered the surgical management in 6/18 cases (33%), while the remaining studies contained mixed NET patients′ cohorts. In contrast, fewer studies explored the prognostic relevance of SSR-targeted imaging at staging in pNETs [ 20 , 52 ]. Majala et al [ 52 ] showed that 68Ga-DOTANOC integrated with 18F-Fluorodeoxyglucose (FDG) PET/CT can predict tumor grade and clinical outcome in non-functioning pNETs.…”

“…In contrast, fewer studies explored the prognostic relevance of SSR-targeted imaging at staging in pNETs [ 20 , 52 ]. Majala et al [ 52 ] showed that 68Ga-DOTANOC integrated with 18F-Fluorodeoxyglucose (FDG) PET/CT can predict tumor grade and clinical outcome in non-functioning pNETs. The authors showed that not only FDG but also 68Ga-SSR imaging has prognostic value in the preoperative setting, being able to predict the histopathological grade.…”

Risk Factors of Lymph Node Metastasis in Patients with Pancreatic Neuroendocrine Tumors (PNETs)

“…The rate of lymph node metastasis that was identified in our study was 38.7%, which is in line with previously published data by Hashim and colleagues, who reported a rate of 37.6% [ 5 ]. Moreover, a 33.3% rate of lymph node metastasis was reported by the PET/CT screening imaging [ 21 ]. However, our rate of 38.7% may be an overestimation of the true incidence of lymph node metastasis due to the exclusion of low-risk patients that did not undergo nodal sampling due to a low degree of suspicion.…”