Dual-Threshold Contouring for [ 68 Ga]Ga-DOTATATE PET/CT and Correlation with Overall Survival in Patients with Neuroendocrine Neoplasms

Accurate contouring for [68Ga]Ga-DOTATATE PET/CT in neuroendocrine neoplasms (NENs) is challenging because of variable physiologic uptake in the liver, spleen, and other organs. This complicates absolute threshold algorithms using a single threshold, even if based on liver uptake (as suggested for [18F]FDG PET/CT by PERCIST). We proposed a [68Ga]Ga-DOTATATE PET/CT contouring algorithm with one threshold for hepatic lesions and another for extrahepatic lesions and investigated their prognostic significance in gastroenteropancreatic NENs (GEP-NENs). Methods: This retrospective study was conducted at Royal North Shore Hospital, Australia. Patients with advanced GEP-NENs who underwent [68Ga]Ga-DOTATATE PET/CT imaging between 2012 and 2020 were eligible for inclusion. Measures of total lesion volume (TLV) were derived using a flat threshold of 4 for extrahepatic lesions and a threshold of 1.5 × liver SUVmean + 2 SD for hepatic lesions, using a semiautomated software workflow with nuclear medicine physician verification. The primary endpoint was overall survival (OS), and the secondary endpoint was time to treatment failure (TTF). Results: In total, 151 patients were included (50% men; median age, 62 y); 38% had pancreatic and 50% had midgut tumors. Median OS was significantly shorter in the high-TLV cohort compared with the low-TLV cohort (41.0 mo vs. not reached; hazard ratio [HR], 2.17; 95% CI, 1.26–3.82; P = 0.006). TTF also was significantly shorter in the high-TLV cohort versus the low-TLV cohort (15.7 mo vs. 25.1 mo; HR, 1.63; 95% CI, 1.11–2.42; P = 0.01). After adjustment for other prognostic factors in a multivariate analysis, high TLV remained a strong independent predictor for poorer OS (HR, 2.25; 95% CI, 1.18–4.44; P = 0.02). Conclusion: Dual-threshold contouring is feasible for [68Ga]Ga-DOTATATE PET/CT, with TLV showing prognostic significance in a cohort with GEP-NENs.