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

Warfvinge, Carl Fredrik LU ; Gustafsson, Johan LU ; Roth, Daniel LU orcid ; Tennvall, Jan LU ; Svensson, Johanna ; Bernhardt, Peter ; Åkesson, Anna ; Wieslander, Elinore LU ; Sundlöv, Anna LU orcid and Sjögreen Gleisner, Katarina LU (2024) In Journal of Nuclear Medicine 65(7). p.1070-1075
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... (More)
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. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Nuclear Medicine
volume
65
issue
7
pages
1070 - 1075
publisher
Society of Nuclear Medicine
external identifiers
  • pmid:38724277
  • scopus:85198040878
ISSN
0161-5505
DOI
10.2967/jnumed.123.266991
language
English
LU publication?
yes
id
7ffe8f8e-c30f-4066-8c6a-35c8bf7f39cd
date added to LUP
2024-09-20 16:56:05
date last changed
2024-09-23 07:46:13
@article{7ffe8f8e-c30f-4066-8c6a-35c8bf7f39cd,
  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 [<sup>177</sup>Lu]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 [<sup>177</sup>Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar–SPECT/CT imaging using [<sup>177</sup>Lu]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.}},
  author       = {{Warfvinge, Carl Fredrik and Gustafsson, Johan and Roth, Daniel and Tennvall, Jan and Svensson, Johanna and Bernhardt, Peter and Åkesson, Anna and Wieslander, Elinore and Sundlöv, Anna and Sjögreen Gleisner, Katarina}},
  issn         = {{0161-5505}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1070--1075}},
  publisher    = {{Society of Nuclear Medicine}},
  series       = {{Journal of Nuclear Medicine}},
  title        = {{Relationship Between Absorbed Dose and Response in Neuroendocrine Tumors Treated with [<sup>177</sup>Lu]Lu-DOTATATE}},
  url          = {{http://dx.doi.org/10.2967/jnumed.123.266991}},
  doi          = {{10.2967/jnumed.123.266991}},
  volume       = {{65}},
  year         = {{2024}},
}