粒子治疗肝细胞癌的长期有效性和安全性的Meta分析

Efficacy and safety of particle therapy for hepatocellular carcinoma:a meta-analysis

目的:系统评价质子、重离子治疗肝细胞癌(hepatocellular carcinoma,HCC)的长期有效性和安全性。方法:系统检索Medline、Embase、Web of Science、中国生物医学文献数据库、万方数据库和中国知网,检索时间均从建库至2022年7月。由2名研究者独立筛选文献、提取资料并评价纳入研究的方法学质量,并进行Meta分析。结果:共纳入20篇文献,其中质子治疗13篇,碳离子治疗8篇,其中1篇文献同时包含碳离子和质子治疗HCC结果,共包括1884例患者。Meta分析结果显示,碳离子和质子治疗HCC可获得较高的长期局部控制率[5年局部控制率分别为90%(95%CI:86%~94%),85%(95%CI:80%~91%)]及可接受的长期生存率[5年总生存率分别为33%(95%CI:23%~43%)、41%(95%CI:32%~50%)]。亚组分析结果表明,碳离子和质子治疗肿瘤病灶小、肝功能Child-Pugh A级、首次治疗、单发肿瘤的HCC患者可取得更好的生存结果。3级以上严重不良事件的发生率均较低。结论:质子、重离子治疗HCC具有良好的局部控制率、可接受的总生存率和较低的复发率。但现有研究文献质量较低,报道不全,尤其是毒性反应方面,因此需要开展更多前瞻性、多中心、高质量研究进行深入探讨。

Objective: To evaluate the efficacy and safety of proton and heavy ion therapy for hepatocellular carcinoma(HCC). Method: Medline, Embase, Web of Science, China Biology Medicine(CBM), Wanfang Database and China National Knowledge Internet(CNKI) were systematically searched from inception to July 2022. Two researchers independently screened the titles and abstracts, extracted the data, and evaluated the methodological quality of the included studies. STATA 14.0 software was used for meta-analysis. Result: Totally 13 proton irradiation and 8 carbon ion irradiation which included 1884 patients were included in our final research. The results of meta-analysis showed that carbon ion and proton irradiation could achieve higher longterm local control(LC) rates {5-year LC rate: 90% [95%(confidence interval, CI): 86%-94%], 85%(95%CI: 80%-91%)} and long-term overall survival(OS) rates for HCC [5-year OS rate: 33%(95%CI: 23%-43%), 41%(95%CI: 32%-50%)]. The results of subgroup analysis showed that HCC patients with small tumor diameter, Child-Pugh grade A, primary treatment and single tumor could achieve better survival outcomes, and the incidence of grade 3 or higher adverse events was low. Conclusion: Proton and heavy ion therapy offer high local control, acceptable overall survival and a low recurrence rate for HCC. However, the existing literature is of low quality and incomplete reporting, especially on toxicity. Therefore,there is a strong need for more prospective, multicenter, and high-quality studies.