Much progress has been made in implementing selective internal radiation therapy (SIRT) as a viable treatment option for hepatic malignancies. However, there is still much need for improved options for calculating the amount of activity to be administered. To make advances towards this goal, this study examines the relationship between predicted biological outcomes of liver tumors via tumor control probabilities (TCP) and parenchyma via normal tissue complication probabilities (NTCP) given variations in absorbed dose prescription methodologies. Thirty-nine glass microsphere treatments in 35 patients with hepatocellular carcinoma or metastatic liver disease were analyzed using 99mTc-MAA SPECT/CT and 90Y PET/CT scans. Predicted biological outcomes corresponding to the single compartment (standard) model and multi-compartment (partition) dosimetry model were compared using our previously derived TCP dose-response curves over a range of 80–150 Gy prescribed absorbed dose to the perfused volume, recommended in the package insert for glass microspheres. Retrospective planning dosimetry was performed on the MAA SPECT/CT; changes from the planned infused activity due to selection of absorbed dose level and dosimetry model (standard or partition) were used to scale absorbed doses reported from 90Y PET/CT including liver parenchyma and lesions (N = 120) > 2 ml. A parameterized charting system was developed across all potential prescription options to enable a clear relationship between standard prescription vs. the partition model-based prescription. Using a previously proposed NTCP model, the change in prescribed dose from a standard model prescription of 120 Gy to the perfused volume to a 15% NTCP prescription to the normal liver was explored. Average TCP predictions for the partition model compared with the standard model varied from a 13% decrease to a 32% increase when the prescribed dose was varied across the range of 80–150 Gy. In the parametrized chart comparing absorbed dose prescription ranges across the standard model and partition models, a line of equivalent absorbed dose to a tumor was identified. TCP predictions on a per lesion basis varied between a 26% decrease and a 81% increase for the most commonly chosen prescription options when comparing the partition model with the standard model. NTCP model was only applicable to a subset of patients because of the small volume fraction of the liver that was targeted in most cases. Our retrospective analysis of patient imaging data shows that the choice of prescribed dose and which model to prescribe potentially contribute to a wide variation in average tumor efficacy. Biological response data should be included as one factor when looking to improve patient care in the clinic. The use of parameterized charting, such as presented here, will help direct physicians when transitioning to newer prescription methods.

中文翻译：

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Y-90 SIRT：跨剂量模型评估 TCP 变化

在实施选择性内部放射治疗 (SIRT) 作为肝脏恶性肿瘤的可行治疗选择方面取得了很大进展。然而，仍然非常需要用于计算要管理的活动量的改进选项。为了朝着这一目标取得进展，本研究通过考虑吸收剂量处方方法的变化，通过肿瘤控制概率 (TCP) 和通过正常组织并发症概率 (NTCP) 来检查肝肿瘤的预测生物学结果之间的关系。使用 99mTc-MAA SPECT/CT 和 90Y PET/CT 扫描分析了 35 名肝细胞癌或转移性肝病患者的 39 次玻璃微球治疗。使用我们先前导出的 TCP 剂量反应曲线比较了对应于单隔室（标准）模型和多隔室（分区）剂量学模型的预测生物学结果，在 80-150 Gy 规定的吸收剂量范围内对灌注体积进行了比较，推荐在玻璃微球的包装说明书。在 MAA SPECT/CT 上进行了回顾性计划剂量测定；由于选择吸收剂量水平和剂量学模型（标准或分区）而导致的计划输注活动的变化用于缩放从 90 年 PET/CT 报告的吸收剂量，包括肝实质和病变 (N = 120) > 2 ml。在所有潜在处方选项中开发了一个参数化图表系统，以实现标准处方与基于分区模型的处方之间的清晰关系。使用先前提出的 NTCP 模型，探索了从 120 Gy 标准模型处方到灌注体积到 15% NTCP 处方到正常肝脏的处方剂量变化。当规定剂量在 80-150 Gy 范围内变化时，分区模型与标准模型相比的平均 TCP 预测值从 13% 下降到 32% 上升不等。在比较标准模型和分区模型的吸收剂量处方范围的参数化图表中，确定了一条肿瘤的等效吸收剂量线。在将分区模型与标准模型进行比较时，对于最常用的处方选项，基于每个病变的 TCP 预测在 26% 和 81% 之间变化。NTCP 模型仅适用于一部分患者，因为在大多数情况下靶向的肝脏体积分数很小。我们对患者影像数据的回顾性分析表明，处方剂量的选择和处方模型可能会导致平均肿瘤疗效的广泛变化。在寻求改善诊所的患者护理时，应将生物反应数据作为一项考虑因素。参数化图表的使用，例如此处介绍的，将有助于指导医生在过渡到新的处方方法时。在寻求改善诊所的患者护理时，应将生物反应数据作为一项考虑因素。参数化图表的使用，例如此处介绍的，将有助于指导医生在过渡到新的处方方法时。在寻求改善诊所的患者护理时，应将生物反应数据作为一项考虑因素。参数化图表的使用，例如此处介绍的，将有助于指导医生在过渡到新的处方方法时。