Ney Douglas E, Carlson Julie A, Damek Denise M, Gaspar Laurie E, Kavanagh Brian D, Kleinschmidt-DeMasters B K, Waziri Allen E, Lillehei Kevin O, Reddy Krishna, Chen Changhu
Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA,
J Neurooncol. 2015 Mar;122(1):135-43. doi: 10.1007/s11060-014-1691-z. Epub 2014 Dec 19.
Bevacizumab blocks the effects of VEGF and may allow for more aggressive radiotherapy schedules. We evaluated the efficacy and toxicity of hypofractionated intensity-modulated radiation therapy with concurrent and adjuvant temozolomide and bevacizumab in patients with newly diagnosed glioblastoma. Patients with newly diagnosed glioblastoma were treated with hypofractionated intensity modulated radiation therapy to the surgical cavity and residual tumor with a 1 cm margin (PTV1) to 60 Gy and to the T2 abnormality with a 1 cm margin (PTV2) to 30 Gy in 10 daily fractions over 2 weeks. Concurrent temozolomide (75 mg/m(2) daily) and bevacizumab (10 mg/kg) was administered followed by adjuvant temozolomide (200 mg/m(2)) on a standard 5/28 day cycle and bevacizumab (10 mg/kg) every 2 weeks for 6 months. Thirty newly diagnosed patients were treated on study. Median PTV1 volume was 131.1 cm(3) and the median PTV2 volume was 342.6 cm(3). Six-month progression-free survival (PFS) was 90 %, with median follow-up of 15.9 months. The median PFS was 14.3 months, with a median overall survival (OS) of 16.3 months. Grade 4 hematologic toxicity included neutropenia (10 %) and thrombocytopenia (17 %). Grades 3/4 non-hematologic toxicity included fatigue (13 %), wound dehiscence (7 %) and stroke, pulmonary embolism and nausea each in 1 patient. Presumed radiation necrosis with clinical decline was seen in 50 % of patients, two with autopsy documentation. The study was closed early to accrual due to this finding. This study demonstrated 90 % 6-month PFS and OS comparable to historic data in patients receiving standard treatment. Bevacizumab did not prevent radiation necrosis associated with this hypofractionated radiation regimen and large PTV volumes may have contributed to high rates of presumed radiation necrosis.
贝伐单抗可阻断血管内皮生长因子（VEGF）的作用，并可能允许采用更积极的放疗方案。我们评估了在新诊断的胶质母细胞瘤患者中，超分割调强放疗联合替莫唑胺和贝伐单抗同步及辅助治疗的疗效和毒性。新诊断的胶质母细胞瘤患者接受超分割调强放疗，照射手术腔及距残留肿瘤边缘1 cm的区域（计划靶体积1，PTV1）至60 Gy，照射距T2异常区域边缘1 cm的区域（计划靶体积2，PTV2）至30 Gy，分10次每日照射，共2周。同步给予替莫唑胺（每日75 mg/m²）和贝伐单抗（10 mg/kg），随后按照标准的5/28天周期给予辅助替莫唑胺（200 mg/m²），并每2周给予贝伐单抗（10 mg/kg），共6个月。30例新诊断患者接受了该研究治疗。PTV1的中位体积为131.1 cm³，PTV2的中位体积为342.6 cm³。6个月无进展生存期（PFS）为90%，中位随访时间为15.9个月。中位PFS为14.3个月，中位总生存期（OS）为16.3个月。4级血液学毒性包括中性粒细胞减少（10%）和血小板减少（17%）。3/4级非血液学毒性包括疲劳（13%）、伤口裂开（7%），以及1例患者出现的中风、肺栓塞和恶心。50%的患者出现伴有临床症状恶化的疑似放射性坏死，其中2例有尸检记录。由于这一发现，该研究提前停止入组。本研究显示6个月PFS和OS为90%，与接受标准治疗患者的历史数据相当。贝伐单抗未能预防与这种超分割放疗方案相关的放射性坏死，且较大的PTV体积可能导致了较高的疑似放射性坏死发生率。
