Inter- and intra-tumoral heterogeneity on [ ⁶⁸ Ga]Ga-DOTA-TATE/[ ⁶⁸ Ga]Ga-DOTA-TOC PET/CT predicts response to [ ¹⁷⁷ Lu]Lu-DOTA-TATE PRRT in neuroendocrine tumor patients.

Publisher: Springer Nature Country of Publication: England NLM ID: 9918752082606676 Publication Model: Electronic Cited Medium: Internet ISSN: 3005-074X (Electronic) Linking ISSN: 3005074X NLM ISO Abbreviation: EJNMMI Rep Subsets: PubMed not MEDLINE

Original Publication: [London] : Springer Nature, [2024]-

Background: 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 [ ¹⁷⁷ Lu]Lu-DOTA-TATE PRRT.
Methods: NET patients who underwent [ ¹⁷⁷ Lu]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.
Results: 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 mean liver-corrected SUVmean were selected for 24-month TTP. The model was not able to significantly predict progression (C-statistic = 0.58, 95% CI 0.50-0.62). Total receptor expression and mean skewness were selected for OS. The resulting model was able to significantly predict death (C-statistic = 0.62, 95% CI 0.53-0.67), but the predictive ability was limited, as evidenced by the low C-statistic.
Conclusions: Our exploratory analysis provides preliminary results showing that imaging indices of inter- and intra-tumor heterogeneity from pretreatment PET/CT images may potentially predict treatment efficacy in NET patients undergoing [ ¹⁷⁷ Lu]Lu-DOTA-TATE therapy. However, prospective evaluation in a larger cohort is needed to further assess whether a comprehensive characterization of tumor heterogeneity within a patient can help guide treatment decisions.
Competing Interests: Declarations. Ethics approval and consent to participate: All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its last amendments or comparable ethical standards. This study was approved by the University of Iowa Institutional Review Board (IRB#200903778). The study was granted a full waiver of HIPAA Authorization (informed consent) based on the DHHS Federal wide Assurance#FWA00003007 for this project involving retrospective secondary analysis of existing data. Consent to participate: Waived by the University of Iowa Institutional Review Board for this retrospective secondary analysis of existing data-please see the above for details. Competing interests: The authors declare that they have no competing interests or relevant financial or non-financial interests to disclose.
(© 2024. The Author(s).)

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Date Created: 20241129 Latest Revision: 20241202

20241204

PMC11607192

10.1186/s41824-024-00227-3

39613925