¹⁶⁶Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose–response relationship and its association with overall survival for ¹⁶⁶Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an ¹⁸F-FDG PET/CT scan at baseline, a posttreatment ¹⁶⁶Ho SPECT/CT scan, and another ¹⁸F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment ¹⁶⁶Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo–based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose–response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178–303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113–191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87–159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose–response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161–274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81–165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose–response relationship in ¹⁶⁶Ho radioembolization. Treatment response is associated with a higher overall survival.

欧盟最近批准了^166个Ho-微球用于肝放射性栓塞的临床应用。这项研究的目的是研究肝转移患者中¹⁶⁶ Ho放射栓塞的吸收剂量-反应关系及其与总生存的关系。方法：在剖检可见我和II期临床研究谁接受了治疗的患者，¹⁸ F-FDG PET / CT扫描基线，硅酸盐，¹⁶⁶何SPECT / CT扫描，另有¹⁸架F-FDG PET / CT扫描在3月龄随访-up进行分析。后处理¹⁶⁶利用定量蒙特卡罗方法，通过定量SPECT / CT重建估计了Ho-微球活性分布。每个肿瘤的反应均基于基线和随访之间总病变糖酵解（TLG）的变化，根据PERCIST标准，将其分为4类中的1种，从完全缓解到进行性疾病。根据每个患者的TLG平均变化将患者水平的反应分组。使用线性混合模型评估吸收的剂量-反应关系，以说明患者体内肿瘤的相关性。使用对数秩检验比较具有和没有代谢性肝反应的患者之间的中位总生存期。结果：纳入了总共98个肿瘤的36例患者。探索了肿瘤吸收剂量与肿瘤水平和患者水平反应之间的关系。在肿瘤水平上，在完全缓解（232 Gy； 95％置信区间[CI]，178–303 Gy；n = 32）和稳定疾病（147 Gy； 95％CI， 113–191 Gy；n = 28）（P = 0.01）以及介于完全缓解和进行性疾病之间（117 Gy； 95％CI，87–159 Gy；n = 21）（P = 0.0008）。这构成了稳健的吸收剂量-反应关系。在患者水平上，发现完全或部分缓解的患者之间存在显着差异（210 Gy； 95％CI，161–274 Gy； 100 Gy；n = 13）和进行性疾病患者（116 Gy; 95％CI，81–165 Gy; n = 9）（P = 0.01）。随后根据患者的TLG平均变化将其分组。客观缓解（完全或部分缓解）患者的总生存期显着高于非缓解（稳定或进行性疾病）患者（中位19 mo vs. 7.5 mo；对数秩，P = 0.01）。结论：这些结果证实了¹⁶⁶ Ho放射性栓塞中存在显着的吸收剂量-反应关系。治疗反应与更高的总生存期有关。