Supplementary Material for: High Metabolic Tumour Volume on 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Poor Survival from Neuroendocrine Neoplasms

Introduction: 18-Fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. ¹⁸F-FDG avidity and high SUV_max have been demonstrated to predict poor outcome. Quantitative metrics of ¹⁸F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs. Methods: Patients with NEN undergoing ¹⁸F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUV_max/SUV_mean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA. Results: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0–3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25–7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUV_max was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV – G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA). Conclusions: Quantitative analysis of ¹⁸F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients.