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

Abstract

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.

Advanced Imaging Techniques for Radiotherapy Planning of Gliomas

“…More recently, a multicenter prospective phase III trial in newly diagnosed GBM (SPECTRO GLIO, trial NCT01507506, estimated study completion date: March 2023) is evaluating the potential survival benefit of a simultaneous integrated boost of IMRT (72Gy/2.4Gy) delivered to the portion of the disease identified by a Cho/NAA > 2 at MRSI [ 55 ].…”

Evaluation of the Impact of Magnetic Resonance Imaging (MRI) on Gross Tumor Volume (GTV) Definition for Radiation Treatment Planning (RTP) of Inoperable High Grade Gliomas (HGGs)

“…In this context, detailed multimodality imaging information may add to the accuracy of target definition in HGGs. The usefulness of neuroimaging with Magnetic Resonance Imaging (MRI) for several purposes including diagnosis, lesion characterization, presurgical planning and navigation for preservation of eloquent brain regions and fiber tracts, brain tumor segmentation, disease monitoring, and discrimination of tumor progression from adverse effects of irradiation has been widely addressed in the literature [13][14][15][16][17][18]. Nevertheless, there is paucity of data on its utility for RT target definition for the distinct group of patients with inoperable HGGs.…”

Radioresistance in Glioblastoma and the Development of Radiosensitizers

“…Therefore, combining the molecular information provided by MRSI with anatomical information from conventional MRI would provide a better strategy for GBM patient management. MRSI has been reported for use in GBM treatment planning and follow-up of patients after radio- and chemotherapy [ 41 , 42 , 43 ]. All these advancements in MRI are crucial for detecting the response of patients to radiotherapy and managing GBM radioresistance.…”