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放疗联合抗 PD-1 与单纯放疗治疗肝细胞癌患者肝毒性。

Radiotherapy plus anti-PD1 versus radiotherapy for hepatic toxicity in patients with hepatocellular carcinoma.

机构信息

Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, China.

Department of Research, Guangxi Medical University Cancer Hospital, Nanning, 530021, China.

出版信息

Radiat Oncol. 2023 Aug 4;18(1):129. doi: 10.1186/s13014-023-02309-1.

Abstract

PURPOSE

In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD.

PATIENTS AND METHODS

Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram.

RESULTS

There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82).

CONCLUSIONS

The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.

摘要

目的

本研究旨在比较肝细胞癌(HCC)患者接受放疗(RT)联合程序性细胞死亡蛋白 1(抗 PD1)抗体与单纯 RT 治疗的放射性肝毒性(RIHT)结局,评估非经典放射性肝损伤(ncRILD)的预后因素,并建立预测 ncRILD 概率的列线图。

方法

回顾性纳入接受 RT 联合抗 PD1(RT+PD1,n=30)或单纯 RT(n=66)治疗的不可切除 HCC 患者。每组(n=30)患者采用倾向评分匹配(PSM)纳入匹配队列。在匹配前后评估并分析治疗相关肝毒性。采用单变量逻辑分析和 Spearman 秩检验在匹配队列中识别影响 ncRILD 的预后因素,以生成列线图。

结果

在 PSM 前,两组间除 AST 升高≥1 级和总胆红素升高≥1 级外,RIHT 无差异。PSM 后,RT+PD1 组更常出现 AST 升高≥1 级(p=0.020),两组间其他肝毒性指标无显著差异。在匹配队列中,V25、肿瘤数目、年龄和凝血酶原时间(PT)是 ncRILD 建模的最佳预后因素。列线图显示出良好的预测性能(曲线下面积=0.82)。

结论

接受 RT+PD1 治疗的 HCC 患者 RIHT 的发生率可接受,与 RT 治疗相似。基于 V25、肿瘤数目、年龄和 PT 的列线图可稳健预测 ncRILD 的概率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee52/10403970/e5d68d2bb4f9/13014_2023_2309_Fig1_HTML.jpg

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