Abstract Background: Digestive Neuroendocrine Neoplasms (DNENs) express in up to 80% of cases somatostatin receptors (SSTRs), that are detected by Functional Imaging Tests (FITs). FITs are needed at DNENs first diagnosis to define therapy but their role in follow-up (FU) is unclear. Moreover, with the introduction of targeted therapies, RECIST criteria are showing difficulties to assess tumor response to these drugs. The aim of this study was to compare the accuracy in detecting new distant metastases (primary outcome) and the clinical usefulness (secondary outcome) of FITs and Computed Tomography scan (CT) in metastatic DNENs FU. Methods Retrospective analysis of stage IV DNENs expressing SSTRs with at least 24 month-FU. From 1995 to 2008 FIT performed was Octreoscan (OCT), from 2008 to 2013 it was 68Ga-DOTANOC PET/CT (GaPET). CT was repeated every 6-12 months, FIT yearly. FU time was divided into 12 month-”units”, in which each patient had at least 1 CT and 1 FIT. Units were analyzed separately and then compared to each other. The gold standard adopted was the result of the imaging tests, the surgical and pathology findings collected for each patient during FU. Clinical usefulness was defined as appropriate changes in management (indication to new imaging test, therapy, surgery or biopsy) due to CT and/or FITs during FU. Results 323 units (median 3 per patient, range 2-7) derived from 99 patients included (66% metastatic since the first diagnosis). New lesions were detected by CT alone in 86.4% of cases, with a positive predictive value (PPV) of 93.3% and a negative predictive value (NPV) of 91.9%; adding OCT, the diagnostic yield was 10.34% (P<0.05; PPV 100%, NPV 98.8%;), while adding GaPET it was 21.7% (P<0.05; PPV 100%, NPV 100%). Appropriate changes were due to CT alone in 84.9% of cases; adding OCT, the diagnostic yield was 11.6% (P<0.05), while with GaPET it was 33.3% (P<0.05). Conclusions The addition of FIT to CT during FU significantly improves the detection rate of new lesions and the clinical management of patients affected by metastatic DNENs. Citation Format: Elettra Merola, Francesco Panzuto, Gabriele Capurso, Patrizia Kump, Rainer Lipp, Noemi Cicchese, Elsa Iannicelli, Daniela Prosperi, Patrizia Pizzichini, Maria Rinzivillo, Stefano Partelli, Anja Rinke, Massimo Falconi, Gianfranco Delle Fave. Functional imaging tests vs. computed tomography scan: detection of new metastases and clinical usefulness in digestive neuroendocrine neoplasms follow-up. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3455. doi:10.1158/1538-7445.AM2015-3455