Division of Neuro-Oncology, Department of Neurology, Feinberg School of Medicine Northwestern University, Chicago, IL, 60611, USA.
Northwestern University, 710 N Lake Shore Drive, Abbott Hall Room 1123, Chicago, IL, 60611, USA.
J Neurooncol. 2021 Dec;155(3):297-306. doi: 10.1007/s11060-021-03875-8. Epub 2021 Oct 24.
Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial.
Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55 Gy to enhancing disease, 45 Gy to non-enhancing disease in 25 fractions) with bevacizumab 10 mg/kg every 2 weeks IV and temozolomide 75 mg/m daily followed by maintenance bevacizumab 10 mg/kg every 2 weeks and temozolomide 50 mg/m daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales.
Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred.
Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.
贝伐单抗耐药的高级别脑胶质瘤患者的生存率较差。我们前瞻性地研究了在没有体积限制的情况下，在一项单臂试验中，对贝伐单抗初治和贝伐单抗暴露的复发性高级别脑胶质瘤患者重新进行放疗、贝伐单抗和替莫唑胺治疗的疗效。
根据世界卫生组织（WHO）分级（4 级与<4 级）和既往贝伐单抗暴露情况（是与否）对复发性高级别脑胶质瘤患者进行分层。符合条件的患者接受放疗，采用同步整合升压技术（增强病变 55Gy，非增强病变 45Gy，25 个分次），同时静脉注射贝伐单抗 10mg/kg，每 2 周 1 次，替莫唑胺 75mg/m2，每日 1 次，随后维持贝伐单抗 10mg/kg，每 2 周 1 次，替莫唑胺 50mg/m2，每日 1 次，持续 6 周，然后休息 2 周，直至疾病进展。主要终点为总生存期。使用 FACT-Br 和 FACT-Fatigue 量表研究生活质量。
共纳入 54 例患者。大多数患者（n=36，67%）为贝伐单抗预处理的胶质母细胞瘤。所有患者的中位总生存期为 8.5 个月，贝伐单抗预处理的胶质母细胞瘤组为 7.9 个月。与放疗<36 个月的患者相比，放疗≥36 个月的患者中位总生存期为 13.3 个月（p<0.01）。FACT-Br 和 FACT-Fatigue 评分在放疗期间最初下降，但恢复到治疗前基线。治疗耐受性良好，5 例患者出现>3 级淋巴细胞减少症，2 例患者出现>3 级血小板减少症。无影像学或临床放射性坏死发生。
贝伐单抗联合替莫唑胺再放疗是一种安全可行的挽救治疗方法，适用于大体积贝伐单抗耐药的高级别脑胶质瘤患者。距初始放疗时间较长的患者可能从该方案中获益更多。
