Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging

BMC Cancer. 2019 Feb 21;19(1):167. doi: 10.1186/s12885-019-5317-x.


Background: 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.

Discussion: 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.

Trial registration: NCT01507506 , registration date December 20, 2011.

Keywords: Clinical trial; Dose-painting; Glioblastoma; Magnetic resonance spectroscopic imaging; Phase III,online prospective quality control; Proton spectroscopy; Radiotherapy; Spectroscopy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Chemoradiotherapy*
  • Diagnostic Imaging
  • Glioblastoma / mortality
  • Glioblastoma / therapy*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Neoplasm Recurrence, Local
  • Prospective Studies
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated / methods*
  • Survival Analysis
  • Temozolomide / therapeutic use*


  • Antineoplastic Agents, Alkylating
  • Temozolomide

Associated data