Evolution of Dosimetric Parameters Through PRRT and Potential Impact on Clinical Practice: Data from the Prospective Phase II LUMEN Study

Overview

Journal EJNMMI Res

Date 2024 Nov 18

PMID 39557730

Authors

Rachele Danieli

Magdalena Mileva

Gwennaelle Marin

Paulus Kristanto

Wendy Delbart

Bruno Vanderlinden

Zena Wimana

Alain Hendlisz

Hugo Levillain

Nick Reynaert

Patrick Flamen

Ioannis Karfis

Affiliations

Soon will be listed here.

Abstract

Background: Peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-DOTA-TATE has emerged as a promising treatment for gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Its treatment protocol is currently standardised for all patients, resulting in different patient outcomes. This study investigates the variability of tumours and organs-at-risk (kidneys and red marrow) dosimetric parameters across treatment cycles in patients with pancreatic and intestinal NETs. Data from 37 patients enrolled in a prospective phase II study (LuMEn) were analysed. Treatment consisted of four cycles of [Lu]Lu-DOTA-TATE administered 8-12 weeks apart. Three-time-point SPECT/CT imaging was performed after each treatment cycle, and dosimetry of tumours and organs-at-risk (kidneys and red marrow) was conducted following the medical internal radiation dose formalism. Coefficients of variation (CoV) assessed the variability of absorbed doses, activity concentrations on day 1, and effective half-lives. Linear mixed effect models (SAS software) were used to investigate the evolution of the dosimetric parameters over cycles, discerning between different primary NET types and grades of tumours.

Results: There is an important variability in absorbed doses and activity concentrations among patients, particularly in tumours (CoV: ~50%). Tumour absorbed doses and activity concentrations decreased over treatment cycles in pancreatic NETs, although at a limited rate (~-13%/cycle). An opposite trend was observed for the kidneys ( ~ + 8%/cycle). Effective half-lives remained relatively constant across cycles for both organs-at-risk and tumours. The primary NET type significantly influenced effective half-lives in tumours, shorter in pancreatic NETs than intestinal NETs (77 h vs. 107 h, p < 0.0001). No significant effect of the grade was observed on either of the variables investigated.

Conclusions: Our study revealed considerable variations in tumour absorbed doses among patients with NETs treated with a standardized protocol. These findings confirm the need for personalized dosimetry approaches in PRRT, considering patient and tumour characteristics.

Trial Registration: EudraCT Number: 2012-003666-41.

Clinicaltrials: gov identifier: NCT01842165. Registered 25 April 2013, https://clinicaltrials.gov/ct2/show/NCT01842165 .

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