Neuro-Oncologie - Neurologie, CHU de Nancy, Hôpital Central, CO no 34, 54035 Nancy Cedex, France.
Neuro Oncol. 2010 Jun;12(6):595-602. doi: 10.1093/neuonc/noq008. Epub 2010 Feb 11.
Ultrafractionation of radiation therapy is a novel regimen consisting of irradiating tumors several times daily, delivering low doses (<0.75 Gy) at which hyperradiosensitivity occurs. We recently demonstrated the high efficiency of ultrafractionated radiotherapy (RT) on glioma xenografts and report here on a phase II clinical trial to determine the safety, tolerability, and efficacy of an ultrafractionation regimen in patients with newly and inoperable glioblastoma (GBM). Thirty-one patients with histologically proven, newly diagnosed, and unresectable supratentorial GBM (WHO grade IV) were enrolled. Three daily doses of 0.75 Gy were delivered at least 4 hours apart, 5 days per week over 6-7 consecutive weeks (90 fractions for a total of 67.5 Gy). Conformal irradiation included the tumor bulk with a margin of 2.5 cm. The primary end points were safety, toxicity, and tolerability, and the secondary end points were overall survival (OS) and progression-free survival (PFS). Multivariate analysis was used to compare the OS and PFS with the EORTC-NCIC trial 26981-22981/CE.3 of RT alone vs radiation therapy and temozolomide (TMZ). The ultrafractionation radiation regimen was safe and well tolerated. No acute Grade III and/or IV CNS toxicity was observed. Median PFS and OS from initial diagnosis were 5.1 and 9.5 months, respectively. When comparing with the EORTC/NCIC trial, in both PFS and OS multivariate analysis, ultrafractionation showed superiority over RT alone, but not over RT and TMZ. The ultrafractionation regimen is safe and may prolong the survival of patients with GBM. Further investigation is warranted and a trial associating ultra-fractionation and TMZ is ongoing.
超分割放射治疗是一种新的治疗方案，包括每天多次照射肿瘤，每次给予低剂量（<0.75Gy），此时会发生超放射敏感性。我们最近证明了超分割放射治疗（RT）在神经胶质瘤异种移植中的高效性，并在此报告一项 II 期临床试验结果，以确定新诊断和不可切除的胶质母细胞瘤（GBM）患者接受超分割方案的安全性、耐受性和疗效。共招募了 31 名经组织学证实的新诊断和不可切除的幕上 GBM（WHO 分级 IV）患者。每天给予 3 次 0.75Gy 的剂量，至少间隔 4 小时，每周 5 天，持续 6-7 周（共 90 次，总剂量为 67.5Gy）。适形照射包括肿瘤肿块和 2.5cm 的边缘。主要终点是安全性、毒性和耐受性，次要终点是总生存期（OS）和无进展生存期（PFS）。采用多变量分析比较 EORTC-NCIC 试验 26981-22981/CE.3 中单独 RT 与 RT 和替莫唑胺（TMZ）的 OS 和 PFS。超分割放射治疗方案安全且耐受性良好。未观察到急性 III 级和/或 IV 级中枢神经系统毒性。从初始诊断到中位 PFS 和 OS 分别为 5.1 个月和 9.5 个月。与 EORTC/NCIC 试验相比，多变量分析中 PFS 和 OS 均显示超分割优于单独 RT，但不优于 RT 和 TMZ。超分割方案安全，可能延长 GBM 患者的生存时间。需要进一步研究，一项联合超分割和 TMZ 的试验正在进行中。
