Clinical usefulness of FDG-PET for management of well-differentiated digestive neuroendocrine tumors

Abstract

Digestive well-differentiated neuroendocrine tumors (NETs) are heterogeneous but share many biological and clinical features. Their main prognostic factors include tumor stage and histopathological grade, which relies on the Ki67 proliferation index [ [1] de Mestier L Lepage C Baudin E et al. Digestive neuroendocrine neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, GTE, RENATEN, TENPATH, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig Liver Dis. 2020; 52: 473-492https://doi.org/10.1016/j.dld.2020.02.011 Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar ]. However, Ki67 assessment may be subject to sampling bias attributable to inter- and intratumor heterogeneity and may not always reflect tumor aggressiveness [ [2] Yang Z Tang LH Klimstra DS Effect of tumor heterogeneity on the assessment of Ki67 labeling index in well-differentiated neuroendocrine tumors metastatic to the liver: implications for prognostic stratification. Am J Surg Pathol. 2011; 35: 853-860https://doi.org/10.1097/PAS.0b013e31821a0696 Crossref PubMed Scopus (237) Google Scholar , [3] de Mestier L Armani M Cros J et al. Lesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors. Dig Liver Dis. 2019; 51: 1720-1724https://doi.org/10.1016/j.dld.2019.06.022 Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar . Hence, additional prognostic evaluation would be of great relevance. The impact of 18fluorodeoxyglucose–positron-emission tomography (FDG-PET) on neuroendocrine neoplasm prognosis is well-recognized. Higher FDG avidity is associated with greater tumor aggressiveness and higher Ki67 index [ 3 de Mestier L Armani M Cros J et al. Lesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors. Dig Liver Dis. 2019; 51: 1720-1724https://doi.org/10.1016/j.dld.2019.06.022 Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar , 4 Bahri H Laurence L Edeline J et al. High prognostic value of 18F-FDG PET for metastatic gastroenteropancreatic neuroendocrine tumors: a long-term evaluation. J Nucl Med. 2014; 55: 1786-1790https://doi.org/10.2967/jnumed.114.144386 Crossref PubMed Scopus (116) Google Scholar , 5 Rinzivillo M Partelli S Prosperi D et al. Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced entero-pancreatic neuroendocrine neoplasms. Oncologist. 2018; 23: 186-192https://doi.org/10.1634/theoncologist.2017-0278 Crossref PubMed Scopus (31) Google Scholar ]. Therefore, FDG-PET has been strongly recommended, in addition to conventional imaging, for the initial work-up of poorly differentiated neuroendocrine carcinomas or NETs defined by a Ki67 index >10% [ [1] de Mestier L Lepage C Baudin E et al. Digestive neuroendocrine neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis, treatment and follow-up (SNFGE, GTE, RENATEN, TENPATH, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFR). Dig Liver Dis. 2020; 52: 473-492https://doi.org/10.1016/j.dld.2020.02.011 Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar , [6] Abgral R Leboulleux S Déandreis D et al. Performance of (18)fluorodeoxyglucose-positron emission tomography and somatostatin receptor scintigraphy for high Ki67 (≥10%) well-differentiated endocrine carcinoma staging. J Clin Endocrinol Metab. 2011; 96: 665-671https://doi.org/10.1210/jc.2010-2022 Crossref PubMed Scopus (79) Google Scholar . In contrast, its clinical usefulness has not yet been clearly established for low-grade digestive NETs because of its relatively low sensitivity in this setting.