She Lei, Su Lin, Liu Chao
Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacology, Engineering Research Center for Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha, China.
Front Oncol. 2022 Aug 4;12:961014. doi: 10.3389/fonc.2022.961014. eCollection 2022.
Glioblastoma is characterized by rich vasculature and abnormal vascular structure and function. Currently, there is no standard treatment for recurrent glioblastoma (rGBM). Bevacizumab (BEV) has established role of inhibiting neovascularization, alleviating hypoxia in the tumor area and activating the immune microenvironment. BEV may exert synergistic effects with re-irradiation (re-RT) to improve the tumor microenvironment for rGBM.
The purpose of this study was to evaluate the safety, tolerability, and efficacy of a combination of BEV and re-RT for rGBM treatment.
In this retrospective study, a total of 26 rGBM patients with surgical pathologically confirmed glioblastoma and at least one event of recurrence were enrolled. All patients were treated with re-RT in combination with BEV. BEV was administered until progression or serious adverse events.
Median follow-up was 21.9 months for all patients, whereas median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.5-9.5 months). In addition, the 6-month and 1-year PFS rates were 65.4% and 28.2%, respectively. The median overall survival (OS), 6-month OS rate, and 1-year OS rate were 13.6 months (95% CI: 10.2-17.0 months), 92.3%, and 67.5%, respectively. The patient showed good tolerance during the treatment with no grade > 3 grade side event and radiation necrosis occurrence rate of 0%. Combined treatment of gross total resection (GTR) before re-RT and concurrent temozolomide during re-RT was an independent prognostic factor that affected both OS and PFS in the whole cohort (OS: 0.067, 95% CI: 0.009-0.521, = 0.010; PFS: 0.238, 95% CI: 0.076-0.744, = 0.038).
In this study, re-RT combined with concurrent and maintenance BEV treatment was safe, tolerable, and effective in rGBM patients. Moreover, GTR before re-RT and selective concurrent temozolomide could further improve patient PFS and OS.
胶质母细胞瘤的特征是血管丰富以及血管结构和功能异常。目前，复发性胶质母细胞瘤（rGBM）尚无标准治疗方法。贝伐单抗（BEV）在抑制新生血管形成、减轻肿瘤区域缺氧以及激活免疫微环境方面已确立作用。BEV可能与再程放疗（re-RT）发挥协同作用，以改善rGBM的肿瘤微环境。
本研究的目的是评估BEV与re-RT联合治疗rGBM的安全性、耐受性和疗效。
在这项回顾性研究中，共纳入26例经手术病理证实为胶质母细胞瘤且至少有一次复发事件的rGBM患者。所有患者均接受re-RT联合BEV治疗。BEV持续给药直至病情进展或出现严重不良事件。
所有患者的中位随访时间为21.9个月；而中位无进展生存期（PFS）为8.0个月（95%置信区间[CI]：6.5 - 9.5个月）。此外，6个月和1年的PFS率分别为65.4%和28.2%。中位总生存期（OS）、6个月OS率和1年OS率分别为13.6个月（95%CI：10.2 - 17.0个月）、92.3%和67.5%。患者在治疗期间耐受性良好，无>3级不良事件，放射性坏死发生率为0%。再程放疗前进行大体肿瘤全切除（GTR）以及再程放疗期间同步使用替莫唑胺的联合治疗是影响整个队列OS和PFS的独立预后因素（OS：0.067，95%CI：0.009 - 0.521，P = 0.010；PFS：0.238，95%CI：0.076 - 0.744，P = 0.038）。
在本研究中，re-RT联合同步及维持BEV治疗对rGBM患者安全、耐受性良好且有效。此外，再程放疗前的GTR以及选择性同步使用替莫唑胺可进一步改善患者的PFS和OS。
