Sullivan Jessica K, Fahey Paul P, Agho Kinglsey E, Hurley Simon P, Feng Zhihui, Day Richard O, Lim David
School of Medicine, Flinders University, South Australia, Australia.
School of Health Sciences, Western Sydney University, New South Wales, Australia.
Neurooncol Pract. 2022 Sep 30;10(1):13-23. doi: 10.1093/nop/npac078. eCollection 2023 Feb.
Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients.
A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures.
Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies ( = 6138) evaluated OS and 5 studies ( = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review.
This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.
包括丙戊酸（VPA）在内的组蛋白去乙酰化酶抑制剂（HDACi）有潜力通过对肿瘤细胞进行表观遗传修饰和放射增敏来提高放射治疗（RT）的疗效并减少治疗不良事件（AE）。本系统评价和荟萃分析旨在评估HDACi作为放射增敏剂用于成人实体器官恶性肿瘤患者的疗效和不良事件。
一项系统评价利用对MEDLINE（Ovid）、Embase（Ovid）、Cochrane图书馆和国际临床试验注册平台的电子检索，以确定研究HDACi治疗对接受RT的实体器官恶性肿瘤患者的疗效和不良事件的研究。荟萃分析以报告为风险比（HR）的总生存期（OS）作为主要结局指标进行。报告为中位生存差异的OS和不良事件为次要结局指标。
10项报告HDACi在接受RT治疗的实体器官恶性肿瘤患者中的疗效和/或不良事件的研究符合纳入标准。所有纳入研究均聚焦于高级别胶质瘤患者中的HDACi丙戊酸（VPA），其中9项研究（n = 6138）评估了OS，5项研究（n = 1055）检查了不良事件。在RT治疗方案中添加VPA可改善OS（HR = 0.80，95%CI 0.67 - 0.96）。没有针对非胶质瘤实体器官恶性肿瘤患者或非VPA HDACi的研究符合本评价的纳入标准。
本评价表明，接受RT的胶质瘤患者可能因给予HDACi VPA而生存期延长。需要进一步的随机对照试验来验证这些发现。此外，有必要对HDACi在非胶质瘤实体器官恶性肿瘤中的放射辅助治疗应用进行更多研究。
