University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
J Nucl Med. 2021 Feb;62(2):272-279. doi: 10.2967/jnumed.120.243832. Epub 2020 Jun 26.
Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relationship between dose and effect (i.e., response and toxicity) in CRC patients treated with Ho radioembolization. CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on posttreatment Ho SPECT/CT. Metabolic response was assessed using the change in total-lesion glycolysis on F-FDG PET/CT between baseline and 3-mo follow-up. Toxicity between treatment and 3 mo was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, and its relationship with parenchyma-absorbed dose was assessed using linear models. The relationship between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. Forty patients were included. The median parenchyma-absorbed dose was 37 Gy (range, 12-55 Gy). New CTCAE grade 3 or higher clinical and laboratory toxicity was present in 8 and 7 patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% CI, 1.18-10.32). On a patient level, metabolic response was as follows: complete response, = 1; partial response, = 11; stable disease, = 17; and progressive disease, = 8. The mean tumor-absorbed dose was 84% higher in patients with complete or partial response than in patients with progressive disease (95% CI, 20%-180%). Survival for patients with a mean tumor-absorbed dose of more than 90 Gy was significantly better than for patients with a mean tumor-absorbed dose of less than 90 Gy (hazard ratio, 0.16; 95% CI, 0.06-0.511). A significant dose-response relationship in CRC patients treated with Ho radioembolization was established, and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use a Ho scout dose to select patients and yo personalize the administered activity, targeting a mean tumor-absorbed dose of more than 90 Gy and a parenchymal dose of less than 55 Gy.
放射性栓塞是治疗无法手术、化疗耐药的结直肠癌（CRC）患者肝转移的一种治疗选择。个性化治疗需要建立剂量阈值。因此，本研究旨在探讨接受 Ho 放射性栓塞治疗的 CRC 患者中剂量与效应（即反应和毒性）之间的关系。分析了在 HEPAR II 和 SIM 研究中接受治疗的 CRC 患者。使用治疗后 Ho SPECT/CT 上的活性分布来估计吸收剂量。使用基线和 3 个月随访期间 F-FDG PET/CT 上总病变糖酵解的变化来评估代谢反应。根据不良事件常用术语标准（CTCAE）第 5 版评估治疗期间和 3 个月时的毒性，并使用线性模型评估其与实质吸收剂量的关系。使用线性混合模型分析肿瘤吸收剂量与患者和肿瘤水平反应之间的关系。使用 100%敏感性作为反应的阈值，确定最小平均肿瘤吸收剂量的阈值，并评估其对生存的影响。 纳入了 40 名患者。实质吸收剂量中位数为 37 Gy（范围 12-55 Gy）。新的 CTCAE 3 级或更高的临床和实验室毒性分别在 8 名和 7 名患者中出现。对于任何临床毒性（每位患者的最高等级），每增加一个 CTCAE 等级类别，实质剂量（Gy）的平均差异为 5.75（95%CI，1.18-10.32）。在患者水平上，代谢反应如下：完全缓解， = 1；部分缓解， = 11；稳定疾病， = 17；进展性疾病， = 8。完全或部分缓解患者的肿瘤吸收剂量平均值比进展性疾病患者高 84%（95%CI，20%-180%）。平均肿瘤吸收剂量大于 90 Gy 的患者的生存明显优于平均肿瘤吸收剂量小于 90 Gy 的患者（风险比，0.16；95%CI，0.06-0.511）。 在接受 Ho 放射性栓塞治疗的 CRC 患者中建立了显著的剂量反应关系，并发现毒性与实质剂量之间存在正相关。对于未来的患者，建议使用 Ho 探查剂量来选择患者，并根据个人情况调整给予的活性，目标是平均肿瘤吸收剂量大于 90 Gy，实质剂量小于 55 Gy。
