Abstract：
OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC.
METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC.
UNASSIGNED: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy.
CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.
METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC.
UNASSIGNED: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy.
CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.
摘要：
目的：姑息性放疗（RT）和全身免疫或靶向治疗在中晚期肝细胞癌（HCC）的治疗中起着重要作用。这些疗法的同时应用正在增加，然而,没有关于全身治疗与RT联合治疗的指南.这篇叙述性综述总结了现有的文献报告在与HCC中常用的RT和免疫或靶向治疗剂同时治疗后观察到的毒性。
方法：在PubMed数据库中搜索了2011年至2023年之间发表的研究，报告了在HCC中同时使用RT和靶向药物治疗的患者的毒性数据。由于HCC的相关文献很少，纳入标准被扩大到包括接受晚期HCC常用靶向治疗的非HCC队列.
■本综述包括67篇文章。22篇文章报道了RT与索拉非尼的联合治疗，一个是Regorafenib,22与贝伐单抗，3人使用lenvatinib，19人使用免疫检查点抑制剂。重要的发现包括联合RT和索拉非尼的高发病率严重肝毒性，肝脏立体定向放疗（SBRT）的0-19％和常规分割肝脏RT的3-18％。贝伐单抗和RT联合治疗时出现严重的胃肠道（GI）毒性，包括穿孔和溃疡，急性设置为0-27%，晚期设置为0-23%。联合免疫检查点阻断剂和RT的安全性与单药治疗相似。
结论：现有数据表明，联合放疗和靶向治疗具有严重不良事件的风险，包括肝毒性和胃肠道毒性。迫切需要未来的研究，专门研究联合治疗对HCC患者的影响，以指导免疫和靶向治疗不断发展的临床决策。
方法：在PubMed数据库中搜索了2011年至2023年之间发表的研究，报告了在HCC中同时使用RT和靶向药物治疗的患者的毒性数据。由于HCC的相关文献很少，纳入标准被扩大到包括接受晚期HCC常用靶向治疗的非HCC队列.
■本综述包括67篇文章。22篇文章报道了RT与索拉非尼的联合治疗，一个是Regorafenib,22与贝伐单抗，3人使用lenvatinib，19人使用免疫检查点抑制剂。重要的发现包括联合RT和索拉非尼的高发病率严重肝毒性，肝脏立体定向放疗（SBRT）的0-19％和常规分割肝脏RT的3-18％。贝伐单抗和RT联合治疗时出现严重的胃肠道（GI）毒性，包括穿孔和溃疡，急性设置为0-27%，晚期设置为0-23%。联合免疫检查点阻断剂和RT的安全性与单药治疗相似。
结论：现有数据表明，联合放疗和靶向治疗具有严重不良事件的风险，包括肝毒性和胃肠道毒性。迫切需要未来的研究，专门研究联合治疗对HCC患者的影响，以指导免疫和靶向治疗不断发展的临床决策。
