Abstract

Purpose

Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([¹⁶⁶Ho]-radioembolization).

Materials and methods

Single center, retrospective study included patients with NELM that received [¹⁶⁶Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (D_t) and whole liver healthy tissue (D_h) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS).

Results

Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 – 82 months). Mean D_t in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a D_t of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1–2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached.

Conclusion

This study confirms the safety and efficacy of [¹⁶⁶Ho]-radioembolization in NELM in a real-world setting. A clear dose–response relationship was demonstrated and future studies should aim at a D_t of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

中文翻译：

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[166Ho]-放射栓塞治疗神经内分泌肿瘤肝转移的剂量-效应关系

摘要

目的

本研究的目的是调查钬166微球放射栓塞治疗神经内分泌肿瘤肝转移（NELM）的剂量反应关系、剂量毒性关系、无进展生存期（PFS）和总生存期（OS）（[ ¹⁶⁶ Ho ]-放射栓塞术）。

材料和方法

单中心回顾性研究包括接受[ ¹⁶⁶ Ho]放射栓塞治疗并进行治疗后SPECT/CT和CECT或MRI成像3个月随访的NELM患者。治疗后SPECT/CT用于计算肿瘤(D _t )和全肝健康组织(D _h )吸收剂量。临床和实验室毒性根据不良事件通用术语标准 (CTCAE) 第 5 版在基线和三个月随访时进行分级。根据 RECIST 1.1 确定疗效。肿瘤和健康剂量与基于病变的客观反应和基于患者的毒性相关。对无进展生存期 (PFS) 和总生存期 (OS) 进行 Kaplan Meier 分析。

结果

包括 25 名患者的 27 次治疗，总共 114 个肿瘤。中位随访时间为 14 个月（3 – 82 个月）。无应答者的平均 D _{t为 68 Gy，而应答者的平均 D t 为 118 Gy，} p  = 0.01。 ROC 分析确定 86 Gy 具有最高的灵敏度和特异性。 83%和81%。实现 ≥ 120 Gy 的 D _t提供了获得响应的最高可能性 (90%)。 16 名患者出现 1-2 级临床毒性，只有 1 名患者出现 3 级临床毒性。未发现明确的健康肝脏剂量毒性关系。中位 PFS 为 15 个月（95% CI [10.2;19.8]），中位 OS 尚未达到。

结论

这项研究证实了在现实环境中 NELM 中[ ¹⁶⁶ Ho]-放射栓塞的安全性和有效性。已证明了明确的剂量-反应关系，未来的研究应以 D _t ≥ 120 Gy 为目标，以预测反应。无法建立剂量-毒性关系。