Inter- and intra-tumoral heterogeneity on 68GaGa-DOTA-TATE/68GaGa-DOTA-TOC PET/CT predicts response to 177LuLu-DOTA-TATE PRRT in neuroendocrine tumor patients

Indices of tumor heterogeneity on somatostatin receptor PET/CT scans may potentially serve as predictive biomarkers of treatment efficacy in neuroendocrine tumor (NET) patients undergoing [177Lu]Lu-DOTA-TATE PRRT.BACKGROUNDIndices of tumor heterogeneity on somatostatin receptor PET/CT scans may potentially serve as predictive biomarkers of treatment efficacy in neuroendocrine tumor (NET) patients undergoing [177Lu]Lu-DOTA-TATE PRRT.NET patients who underwent [177Lu]Lu-DOTA-TATE therapy at the University of Iowa from August 2018 to February 2021 were retrospectively evaluated. Radiomic features on the pre-PRRT somatostatin receptor PET/CT were evaluated using a custom MIM Software® LesionID workflow. Conventional PET/CT metrics of tumor burden, such as somatostatin receptor expression and tumor volume, were calculated in addition to the indices of tumor heterogeneity for each lesion (intra-lesional) and then summarized across all lesions throughout the body (inter-lesional). Endpoints included post-PRRT 24-month time to progression (TTP) and overall survival (OS). Cox regression models were used to assess the predictive ability of the imaging factors on post-PRRT 24-month TTP and OS. LASSO-penalized Cox regression was used to build a multivariable model for each outcome.METHODSNET patients who underwent [177Lu]Lu-DOTA-TATE therapy at the University of Iowa from August 2018 to February 2021 were retrospectively evaluated. Radiomic features on the pre-PRRT somatostatin receptor PET/CT were evaluated using a custom MIM Software® LesionID workflow. Conventional PET/CT metrics of tumor burden, such as somatostatin receptor expression and tumor volume, were calculated in addition to the indices of tumor heterogeneity for each lesion (intra-lesional) and then summarized across all lesions throughout the body (inter-lesional). Endpoints included post-PRRT 24-month time to progression (TTP) and overall survival (OS). Cox regression models were used to assess the predictive ability of the imaging factors on post-PRRT 24-month TTP and OS. LASSO-penalized Cox regression was used to build a multivariable model for each outcome.Eighty patients with a mean age of 65.1 years were included, with most (71.3%) completing 4 cycles of PRRT. Median TTP was 19.1 months, and OS at 60 months was 50%. A large degree of variability between patients was evidenced for imaging features related to somatostatin receptor expression. On multivariable analysis, total receptor expression and