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个体化放射性栓塞治疗难治性肝内胆管细胞癌:一项多中心研究。

Personalised radioembolization improves outcomes in refractory intra-hepatic cholangiocarcinoma: a multicenter study.

机构信息

Nuclear Medicine Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.

Data Center Department, Jules Bordet Institute, Université Libre de Bruxelles, 1 rue Héger-Bordet, 1000, Brussels, Belgium.

出版信息

Eur J Nucl Med Mol Imaging. 2019 Oct;46(11):2270-2279. doi: 10.1007/s00259-019-04427-z. Epub 2019 Jul 19.

Abstract

PURPOSE

Reported outcomes of patients with intra-hepatic cholangiocarcinoma (IH-CCA) treated with radioembolization are highly variable, which indicates differences in included patients' characteristics and/or procedure-related variables. This study aimed to identify patient- and treatment-related variables predictive for radioembolization outcome.

METHODS

This retrospective multicenter study enrolled 58 patients with unresectable and chemorefractory IH-CCA treated with resin Y-microspheres. Clinicopathologic data were collected from patient records. Metabolic parameters of liver tumor(s) and presence of lymph node metastasis were measured on baseline F-FDG-PET/CT. Tc-MAA tumor to liver uptake ratio (TLR) was computed for each lesion on the SPECT-CT. Activity prescription using body-surface-area (BSA) or more personalized partition-model was recorded. The study endpoint was overall survival (OS) starting from date of radioembolization. Statistical analysis was performed by the log-rank test and multivariate Cox's proportional hazards model.

RESULTS

Median OS (mOS) post-radioembolization of the entire cohort was 10.3 months. Variables associated with significant differences in terms of OS were serum albumin (hazard ratio (HR) = 2.78, 95%CI:1.29-5.98, p = 0.002), total bilirubin (HR = 2.17, 95%CI:1.14-4.12, p = 0.009), aspartate aminotransferase (HR = 2.96, 95%CI:1.50-5.84, p < 0.001), alanine aminotransferase (HR = 2.02, 95%CI:1.05-3.90, p = 0.01) and γ-GT (HR = 2.61, 95%CI:1.31-5.22, p < 0.001). The presence of lymph node metastasis as well as a TLR < 1.9 were associated with shorter mOS: HR = 2.35, 95%CI:1.08-5.11, p = 0.008 and HR = 2.92, 95%CI:1.01-8.44, p = 0.009, respectively. Finally, mOS was significantly shorter in patients treated according to the BSA method compared to the partition-model: mOS of 5.5 vs 14.9 months (HR = 2.52, 95%CI:1.23-5.16, p < 0.001). Multivariate analysis indicated that the only variable that increased outcome prediction above the clinical variables was the activity prescription method with HR of 2.26 (95%CI:1.09-4.70, p = 0.03). The average mean radiation dose to tumors was significantly higher with the partition-model (86Gy) versus BSA (38Gy).

CONCLUSION

Radioembolization efficacy in patients with unresectable recurrent and/or chemorefractory IH-CCA strongly depends on the tumor radiation dose. Personalized activity prescription should be performed.

摘要

目的

接受放射性栓塞治疗的肝内胆管细胞癌(IH-CCA)患者的报告结果差异很大,这表明患者特征和/或与治疗相关的变量存在差异。本研究旨在确定与放射性栓塞治疗结果相关的患者和治疗相关变量。

方法

本回顾性多中心研究纳入了 58 名接受不可切除和化疗耐药的 IH-CCA 树脂 Y 微球治疗的患者。从患者病历中收集临床病理数据。在基线 F-FDG-PET/CT 上测量肝肿瘤的代谢参数和淋巴结转移的存在情况。使用体表面积(BSA)或更个性化的分区模型记录 Tc-MAA 肿瘤与肝脏摄取比(TLR)。记录使用 BSA 或更个性化的分区模型进行的放射性栓塞治疗的活性处方。研究终点是从放射性栓塞治疗开始的总生存期(OS)。使用对数秩检验和多变量 Cox 比例风险模型进行统计分析。

结果

整个队列接受放射性栓塞治疗后的中位 OS(mOS)为 10.3 个月。与 OS 显著相关的变量包括血清白蛋白(风险比(HR)=2.78,95%CI:1.29-5.98,p=0.002)、总胆红素(HR=2.17,95%CI:1.14-4.12,p=0.009)、天冬氨酸转氨酶(HR=2.96,95%CI:1.50-5.84,p<0.001)、丙氨酸转氨酶(HR=2.02,95%CI:1.05-3.90,p=0.01)和γ-GT(HR=2.61,95%CI:1.31-5.22,p<0.001)。存在淋巴结转移和 TLR<1.9 与较短的 mOS 相关:HR=2.35,95%CI:1.08-5.11,p=0.008 和 HR=2.92,95%CI:1.01-8.44,p=0.009,分别。最后,与分区模型相比,根据 BSA 方法治疗的患者的 mOS 明显更短:mOS 为 5.5 与 14.9 个月(HR=2.52,95%CI:1.23-5.16,p<0.001)。多变量分析表明,唯一能提高临床变量预测效果的变量是活性处方方法,HR 为 2.26(95%CI:1.09-4.70,p=0.03)。分区模型的肿瘤平均辐射剂量明显高于 BSA(86Gy)(38Gy)。

结论

不可切除复发性和/或化疗耐药的 IH-CCA 患者的放射性栓塞治疗效果强烈取决于肿瘤的辐射剂量。应进行个性化的活性处方。

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