通过肽受体放射性核素治疗（PRRT）的剂量学参数演变及其对临床实践的潜在影响：来自前瞻性II期LUMEN研究的数据

Evolution of dosimetric parameters through PRRT and potential impact on clinical practice: data from the prospective phase II LUMEN study.

作者信息

Danieli Rachele, Mileva Magdalena, Marin Gwennaëlle, Kristanto Paulus, Delbart Wendy, Vanderlinden Bruno, Wimana Zéna, Hendlisz Alain, Levillain Hugo, Reynaert Nick, Flamen Patrick, Karfis Ioannis

机构信息

Medical Physics Department, ENETS Centre of Excellence, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Brussels, Belgium.

Radiophysics and MRI Physics Laboratory (ULB836), Université Libre de Bruxelles (ULB), Brussels, Belgium.

出版信息

EJNMMI Res. 2024 Nov 18;14(1):110. doi: 10.1186/s13550-024-01163-w.

DOI:10.1186/s13550-024-01163-w

PMID:39557730

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11574229/

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 .

摘要

背景

使用[镥]镥-多胺基多羧基-奥曲肽（[Lu]Lu-DOTA-TATE）的肽受体放射性核素治疗（PRRT）已成为胃肠胰神经内分泌肿瘤（GEP-NETs）一种有前景的治疗方法。其治疗方案目前对所有患者都是标准化的，导致不同的患者治疗结果。本研究调查胰腺和肠道神经内分泌肿瘤患者在治疗周期中肿瘤及危及器官（肾脏和红骨髓）剂量学参数的变异性。分析了纳入一项前瞻性II期研究（LuMEn）的37例患者的数据。治疗包括四个周期的[Lu]Lu-DOTA-TATE，间隔8 - 12周给药。每个治疗周期后进行三次SPECT/CT成像，并按照医学内照射剂量学形式对肿瘤及危及器官（肾脏和红骨髓）进行剂量测定。变异系数（CoV）评估吸收剂量、第1天的活度浓度和有效半衰期的变异性。使用线性混合效应模型（SAS软件）研究剂量学参数在各周期的变化情况，区分不同原发神经内分泌肿瘤类型和肿瘤分级。

结果

患者之间吸收剂量和活度浓度存在重要变异性，尤其是在肿瘤中（CoV：约50%）。胰腺神经内分泌肿瘤中，肿瘤吸收剂量和活度浓度在治疗周期中降低，尽管速率有限（约-13%/周期）。肾脏则观察到相反趋势（约+8%/周期）。对于危及器官和肿瘤，有效半衰期在各周期中保持相对恒定。原发神经内分泌肿瘤类型对肿瘤的有效半衰期有显著影响，胰腺神经内分泌肿瘤的有效半衰期短于肠道神经内分泌肿瘤（77小时对107小时，p < 0.0001）。未观察到肿瘤分级对所研究的任何变量有显著影响。