Purpose

To evaluate dosimetry, dose–response and dose-toxicity relationships for holmium-166 (¹⁶⁶Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).

Methods

Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent ¹⁶⁶Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.

Results

Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44—332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 – 48 Gy) and based on target liver volume was 30 Gy (range 13 – 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.

Conclusion

This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with ¹⁶⁶Ho-microspheres.

中文翻译：

---

Holmium-166 放射栓塞剂量测定治疗 HCC

 目的

评估肝细胞癌 （HCC） 患者钬 166 （¹⁶⁶Ho） 放射栓塞的剂量学、剂量反应和剂量毒性关系。

 方法

31 例肝细胞癌患者被纳入 HEPAR Primary 研究 （NCT03379844，于 2017 年 12 月 20 日注册），并接受了 ¹⁶⁶例 Ho 微球放射栓塞术。线性混合模型在肿瘤和患者水平上基于 mRECIST 评估了肿瘤吸收剂量与反应之间的关联。根据预测价值估计初步肿瘤吸收剂量阈值。线性回归模型评估了非肿瘤吸收剂量与不良事件通用术语标准 4.03 版之间的关联。

 结果

中位肿瘤吸收剂量 （肿瘤水平） 为 95.5 Gy （范围 44—332 Gy）。基于全肝体积的中位非肿瘤吸收剂量为 19 Gy（范围 3 – 48 Gy），基于目标肝脏体积的中位非肿瘤吸收剂量为 30 Gy（范围 13 – 54 Gy）。非肿瘤吸收剂量与毒性之间存在显着关联。部分缓解/完全缓解 （PR/CR，缓解者） 的吸收剂量比疾病进展/疾病稳定的肿瘤 （PD/SD，无反应者） 高 41% （95%CI： 2%-93%，p = 0.04）。在肿瘤吸收剂量阈值为 90 Gy 时观察到 155% 的肿瘤反应预测值，在 184.5 Gy 时达到 100% 的预测值。

 结论

本研究证实了肿瘤吸收剂量与反应之间以及非肿瘤吸收剂量与毒性之间的正相关关系。本研究中发现的剂量阈值可作为接受 ¹⁶⁶个 Ho 微球治疗的 HCC 患者个性化剂量测定的基础。