Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE

Carl Fredrik Warfvinge; Johan Gustafsson; Daniel Roth; Jan Tennvall; Johanna Svensson; Peter Bernhardt; Anna Åkesson; Elinore Wieslander; Anna Sundlöv; Katarina Sjögreen Gleisner

doi:10.2967/jnumed.123.266991

Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [¹⁷⁷Lu]Lu-DOTATATE

J Nucl Med. 2024 May 9:jnumed.123.266991. doi: 10.2967/jnumed.123.266991. Online ahead of print.

Authors

Affiliations

¹ Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden; carl_fredrik.warfvinge@med.lu.se.
² Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
³ Medical Radiation Physics, Lund University, Lund, Sweden.
⁴ Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶ Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and.
⁷ Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden.
⁸ Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund, Sweden.

PMID: 38724277
DOI: 10.2967/jnumed.123.266991

Abstract

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [¹⁷⁷Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [¹⁷⁷Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [¹⁷⁷Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm³ were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes.

Keywords: [177Lu]Lu-DOTATATE; dose response; dosimetry; neuroendocrine; radionuclide therapy; tumor.