Radiation Oncology Department, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, INSERM, UPS, Toulouse, France.
BMC Cancer. 2019 Feb 21;19(1):167. doi: 10.1186/s12885-019-5317-x.
Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival.
METHODS/DESIGN: In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status.
This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging.
NCT01507506 , registration date December 20, 2011.
胶质母细胞瘤是一种高级别的胶质浸润性肿瘤，是成人中最常见的恶性脑肿瘤，预后极差。外照射放疗（EBRT）可提高总生存率，但由于局部复发，尤其是在照射野内，生存率仍然较低。由于磁共振波谱成像上胆碱/N-乙酰天门冬氨酸的比值（CNR2）>2 已被描述为局部复发部位的预测指标，我们假设对这些区域进行剂量递增会增加局部控制率，从而提高总体生存率。
方法/设计：在这项新诊断胶质母细胞瘤的多中心前瞻性 III 期试验中，计划对 220 例接受活检或手术的患者进行随机分组到两个治疗组。A 组为 Stupp 方案（增强对比剂的 EBRT 60Gy+2cm 边缘同步替莫唑胺（TMZ）治疗和 6 个月 TMZ 维持治疗）；B 组为相同的治疗方案，在磁共振波谱成像代谢体积上的 CNR2>2 以及增强病变或切除腔中，对 CHO/NAA>2 的区域进行同步整合强度调制放疗（IMRT）的额外同步综合增敏放疗，剂量为 72Gy/2.4Gy。分层因素为手术和 MGMT 状态。
这是一项剂量绘制试验，即根据代谢成像引导给予不均匀剂量。主要终点是总生存率。在实验组中进行在线前瞻性容积和剂量质量控制。该研究将产生大量的纵向多模态磁共振成像数据，包括计划 CT、放射治疗剂量学、磁共振波谱、弥散和灌注成像。
NCT01507506，注册日期为 2011 年 12 月 20 日。
