Abstract
[177Lu]Lu-DOTATATE is an established treatment for metastasized neuroendocrine tumors (NETs). It is postulated that a higher tumor absorbed dose (AD) improves clinical efficacy. The aim of this study was to assess the average AD of the entire tumor burden and analyze its effect on survival outcomes. Methods: This post hoc analysis included 81 patients with metastasized grade 1 and grade 2 NETs treated with [177Lu]Lu-DOTATATE individualized based on renal dosimetry. Tumor ADs were quantified using quantitative SPECT imaging and mass-weighted averaging across all lesions. Patients were stratified into high- and low-AD groups based on median ADs for cycle 1 and cumulative AD over all cycles. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. Results: Higher tumor AD was significantly associated with improved progression-free survival and overall survival. In multivariable analysis, patients in the high-AD group had significantly lower hazard ratios (HRs) for progression-free survival (HR, 0.34 for cycle 1; HR, 0.37 for cumulative AD) and overall survival (HR, 0.41 for cycle 1; HR, 0.48 for cumulative AD). Patients with a cumulative AD of 118 Gy or more (top quartile) had significantly improved survival compared with the remaining cohort, without increased toxicity. Conclusion: Mean tumor AD to the entire tumor burden is an independent predictor of survival in patients with grade 1 and grade 2 NETs treated with [177Lu]Lu-DOTATATE. These findings support the use of tumor dosimetry in treatment planning and suggest that a target AD of around 118 Gy is clinically relevant.