Full-Body Tumor Response Heterogeneity of Metastatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor...

Patients with metastatic neuroendocrine tumors (NETs) can present with hundreds of lesions, and each lesion might have a unique response pattern to peptide receptor radiopharmaceutical therapy (PRRT). This response heterogeneity has been observed but is poorly understood. In this work, we perform a quantitative analysis of longitudinal PET/CT scans to comprehensively characterize the NET response to PRRT. Methods: NET patients treated with [¹⁷⁷Lu]Lu-DOTATATE PRRT imaged at baseline, during, and after PRRT with [⁶⁸Ga]Ga-DOTATATE PET/CT were enrolled in this retrospective single-institutional study. A deep-learning model was used to identify and contour regions of nonphysiological elevated tracer uptake (lesion-regions of interest [ROIs]). An automated analysis was performed to identify, contour, and quantify the individual lesion-ROI uptake, match ROI between time points, and categorize each lesion-ROI as disappearing, decreasing (ΔSUV_total < -30%), stable (-30% ≤ ΔSUV_total ≤ 30%), increasing (ΔSUV_total > 30%), or new. A patient was considered to have response heterogeneity if both new or increasing lesion-ROIs and decreasing or disappearing lesion-ROIs were present after therapy. Results: Eighteen patients who received between 2 and 7 [⁶⁸Ga]Ga-DOTATATE PET/CT scans were enrolled. In total, 3,289 lesion-ROIs were contoured in the 67 scans acquired (median of 24 lesion-ROIs per image), and 1,459 lesion-ROI tracks, defined as the path that each unique lesion-ROI follows across all time points, were determined by the ROI tracking method (median of 49 tracks per patient). All patients presented with disease response heterogeneity at the first follow-up scan. All 10 patients with more than 1 follow-up scan showed nonmonotonic change in lesion-ROI uptake. Of 129 tracks containing new lesion-ROIs at the first follow-up, 80 (62%) eventually resolved on final follow-up, whereas only 12% (7/60) of the tracks with lesion-ROIs disappearing at the first follow-up scan returned on final follow-up. Conclusion: To the best of our knowledge, this is the first study to evaluate response comprehensively and quantitatively in terms of individual lesion-ROIs. Response heterogeneity was observed in 100% of the patients, which suggests that comprehensive, lesion-level, response assessment is vital for the accurate understanding of the NET response to PRRT.