治疗前的SSTR PET能预测177Lu-DOTATATE肾吸收剂量吗?来自多中心数据的发现

Azadeh Akhavanallaf, Zhonglin Lu, Avery B. Peterson, Johan Blakkisrud, Sara Kurkowska, Surekha Yadav, Chang Wang, Carlos Uribe, Caroline Stokke, Arman Rahmim, Ka Kit Wong, Jean-Mathieu Beauregard, Thomas A. Hope, Katarina Sjögreen Gleisner, Yuni K. Dewaraja
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引用次数: 0

摘要

在对神经内分泌肿瘤进行177Lu-DOTATATE治疗之前,目前使用生长抑素受体(SSTR) PET成像来确认肿瘤是否有足够的SSTR表达,但它也有可能通过预测关键器官的吸收剂量来个性化治疗。本研究旨在验证SSTR PET在预测177Lu-DOTATATE第一周期肾脏吸收剂量方面的预测能力,使用多中心数据集分析并从更广泛的患者群体中获得见解。方法:本研究纳入了来自5个中心的回顾性数据:1个在加拿大(n = 25), 1个在挪威(n = 75), 1个在瑞典(n = 18), 2个在美国(n = 36和26)。在每个中心,根据特定部位的方案进行治疗前SSTR PET/CT成像和周期后基于1 177Lu成像的剂量测定。采用基线SSTR PET肾脏摄取值预测177Lu-DOTATATE的肾脏吸收剂量,建立混合效应模型,将中心视为随机效应。此外,对外部验证和内部验证分别进行留一中心交叉验证和留一样本交叉验证,测量平均绝对误差和平均相对绝对误差。结果:在所有参与研究的中心,第1周期肾脏吸收剂量中位数为0.56 Gy/GBq(范围,0.14-1.27 Gy/GBq),而治疗前SSTR PET肾脏摄取中位数为110.7 Bq/mL/MBq(范围,28.6-287.7 Bq/mL/MBq)。吸收剂量和PET摄取的中心均值差异均有统计学意义(P <;单因素方差分析0.0001)。P <;各中心肾SSTR PET摄取与177Lu-DOTATATE吸收剂量呈正相关(中心特异性决定系数为0.14 ~ 0.53)。当汇总所有中心的数据时,混合效应模型的决定系数达到0.25 (P <;0.01),平均绝对误差为0.15 Gy/GBq (SD, 0.11 Gy/GBq),外部验证的平均相对绝对误差为28% (SD, 24%),内部验证的平均相对绝对误差为0.12 Gy/GBq (SD, 0.10 Gy/GBq)和22% (SD, 20%)。结论:在多中心人群中观察到的SSTR PET肾脏摄取与177Lu-DOTATATE肾脏吸收剂量之间的相关性具有统计学意义,但并不明显。预测模型在pet预测吸收剂量的外部和内部验证中实现了平均相对绝对误差28%或更小。中心间的差异表明需要标准化的成像方案和剂量学工作流程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Can 177Lu-DOTATATE Kidney Absorbed Doses be Predicted from Pretherapy SSTR PET? Findings from Multicenter Data

Before performing 177Lu-DOTATATE therapy for neuroendocrine tumors, somatostatin receptor (SSTR) PET imaging is currently used to confirm sufficient tumor SSTR expression, but it also has potential to be used to personalize treatment by predicting absorbed doses to critical organs. This study aims to validate the predictive capability of SSTR PET in anticipating renal absorbed dose in the first cycle of 177Lu-DOTATATE using a multicenter dataset to analyze and derive insights from a broader patient population. Methods: Retrospective data from 5 centers were included in this study: 1 in Canada (n = 25), 1 in Norway (n = 75), 1 in Sweden (n = 18), and 2 in the United States (n = 36 and n = 26). At each center, pretherapy SSTR PET/CT imaging and postcycle 1 177Lu imaging–based dosimetry were performed according to site-specific protocols. The mixed-effects model treating centers as random effects was developed using baseline SSTR PET renal uptake values to predict renal absorbed dose from 177Lu-DOTATATE. Additionally, leave-one-center-out cross-validation and leave-one-sample-out cross-validation were implemented for external and internal validation, respectively, measuring mean absolute error and mean relative absolute error. Results: Across all participating centers, the median cycle 1 renal absorbed dose was 0.56 Gy/GBq (range, 0.14–1.27 Gy/GBq), whereas the median pretherapy SSTR PET renal uptake was 110.7 Bq/mL/MBq (range, 28.6–287.7 Bq/mL/MBq). The differences among center means were statistically significant for both absorbed dose and PET uptake (P < 0.0001 from 1-way ANOVA). A significant (P < 0.05) correlation was observed between kidney SSTR PET uptake and 177Lu-DOTATATE absorbed dose for each center (center-specific coefficient of determination ranged from 0.14 to 0.53). When data across all centers were aggregated, the mixed-effects model achieved a coefficient of determination of 0.25 (P < 0.01), resulting in an mean absolute error of 0.15 Gy/GBq (SD, 0.11 Gy/GBq) and an mean relative absolute error of 28% (SD, 24%) for external validation and 0.12 Gy/GBq (SD, 0.10 Gy/GBq) and 22% (SD, 20%) for internal validation. Conclusion: The correlations observed between SSTR PET renal uptake and 177Lu-DOTATATE absorbed dose to kidneys across a multicenter population are statistically significant yet modest. The prediction model achieved a mean relative absolute error 28% or less for both external and internal validation of PET-predicted absorbed doses. The intercenter differences suggest the need for standardized imaging protocols and dosimetry workflows.

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