The predictive impact of dual somatostatin receptor/fluorodeoxyglucose (FDG) positron emission tomography (PET) in metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs): review of literature and a single institution experience

Treatment with radiolabelled somatostatin analogs, a form of peptide receptor radionuclide therapy (PRRT), has changed the management of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). There is a subgroup of patients who have suboptimal benefit and rapidly progress on PRRT, indicating that accurate prognostic and predictive markers are urgently needed. Currently, most of the literature concentrate on the prognostic impact of the dual positron emission tomography (PET) scan with very few information regarding the predictive value. We report a case series and review the literature to summarizes the predictive value of combined somatostatin receptor (SSTR) and fluorodeoxyglucose (FDG) PET in metastatic GEP-NETs. We conducted a review of the literature for data published from 2010 to 2021 in MEDLINE, Embase, the National Institutes of Health trial registry, Cochrane CENTRAL, and published proceedings from major gastrointestinal and neuroendocrine cancer meetings. Our main criteria included all published prospective and retrospective data in which the predictive value of dual PET scans using SSTR and FDG was correlated with PRRT response in patients with metastatic GEP-NETs. We summarized clinical outcomes including progression-free survival (PFS), overall survival (OS), and post-therapy complications associated with PRRT according to FDG avidity. We excluded studies that did not include FDG PET scan, GEP patients, studies with no clear predictive value of the FDG PET scan, and studies that did not report a direct correlation between FDG avidity and primary outcome. Additionally, we summarized our institutional experience in eight patients who progressed during or within the first year of PRRT treatment. Our search identified 1306 articles; most of them showed only the prognostic value of Integrated SSTR/FDG PET imaging biomarker in GEP-NETs. Only three studies (n=75 patients) met our inclusion criteria and retrospectively investigated the predictive value of dual SSTR and FDG imaging in subjects being considered for PRRT. The results confirmed that FDG avidity correlates with advanced NET grades. Lesions that are both SSTR and FDG avid had early disease progression. In one study, at multivariate analysis, FDG PET results were independently predictive of lower PFS for PRRT. In our case series, there were eight patients with metastatic well-differentiated GEP-NETs (grades 2 and 3) who progressed within one year of PRRT. Seven of them had positive FDG PET scan at the time of progression. In conclusion, Dual SSTR/FDG PET imaging has a potential predictive impact for PRRT in GEP-NETs. It permits the capturing of the disease complexity and aggressiveness, which correlates with PRRT response. Therefore, prospective future trials should validate the predictive value of dual SSTRs/FDG PET for better PRRT stratification.

[1]  D. Metz,et al.  The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors , 2020, Pancreas.

[2]  R. Baum,et al.  Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients , 2018, The Journal of Nuclear Medicine.

[3]  Shouhao Zhou,et al.  Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States , 2017, JAMA oncology.

[4]  J. Berlin,et al.  Phase 3 Trial of 177Lu‐Dotatate for Midgut Neuroendocrine Tumors , 2017, The New England journal of medicine.

[5]  I. Virgolini,et al.  Direct comparison of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[6]  M. Cuggia,et al.  High Prognostic Value of 18F-FDG PET for Metastatic Gastroenteropancreatic Neuroendocrine Tumors: A Long-Term Evaluation , 2014, The Journal of Nuclear Medicine.

[7]  D. Lee,et al.  Effect of Peptide Receptor Radionuclide Therapy on Somatostatin Receptor Status and Glucose Metabolism in Neuroendocrine Tumors: Intraindividual Comparison of Ga-68 DOTANOC PET/CT and F-18 FDG PET/CT , 2011, International journal of molecular imaging.

[8]  M. Cuggia,et al.  Predictive Value of 18F-FDG PET and Somatostatin Receptor Scintigraphy in Patients with Metastatic Endocrine Tumors , 2009, Journal of Nuclear Medicine.

[9]  J. Polak,et al.  Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas , 1971, Gut.

[10]  Eva Segelov,et al.  The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors , 2017, Pancreas.