Cumulative Absorbed Dose and Successive Cyclic Reduction in Absorbed Dose Predict Response to ¹⁷⁷ Lu-DOTATATE in Neuroendocrine Tumors

The aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [¹⁷⁷Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. <b>Methods:</b> Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [¹⁷⁷Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. <b>Results:</b> A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (<i>P</i> = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. <b>Conclusion:</b> Both AD and changes in AD/AA were independently associated with radiologic response to [¹⁷⁷Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [¹⁷⁷Lu]Lu-DOTATATE trials.