Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial)

Abstract

PURPOSE Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since Magnetic Resonance Spectroscopic Imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. PATIENTS AND METHODS In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. RESULTS One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% IC [42.5; 45.5]), median OS was 22.6 months (95% IC [18.9;25.4]) versus 22.2 months (95% IC [18.3;27.8]) for HD, and median progression-free survival was 8.6 (95% IC [6.8;10.8]) versus 7.8 months (95% IC [6.3;8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% IC [23.2; NR]) for HD patients versus 28.5 months (95% IC [21.1; 35.7]) for SD patients. CONCLUSION The additional MRSI-guided irradiation dose totaling 72 Gy was well-tolerated but did not improve OS in newly diagnosed GBM.

Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12)

“…Additionally, MR spectroscopy might be somewhat less suitable for boost delineation compared to FET PET. An intriguing aspect of the study's results is the high OS outcome observed in the control cohort, as noted by Shu et al in a letter [42] , and the absence of a difference in the rate of radiation necrosis [40] . Compared to these results, Tsien et al (2019) presented encouraging outcomes regarding dose-escalation in their study [11] .…”

“…Notably, the 1-year survival rate stood at 92 %, with a median OS of 20 months observed among the 13 patients who had received a radiation boost targeting both hypercellular and hyperperfused tumor regions [19] . The most recently published trial exploring dose escalation is the SPECTRO GLIO trial using a slightly different approach by utilizing MRI spectroscopy to define the region which should receive dose escalation to 72 Gy [40] . Median OS and median PFS was 22.6 months and 22.2 months, and 8.6 and 7.8 months, in the cohort with and without dose escalation, respectively.…”

Enhancing Whole-Brain Magnetic Field Homogeneity for 3D-Magnetic Resonance Spectroscopic Imaging with a Novel Unified Coil: A Preliminary Study

“…The difficulty in accurately identifying tumor margins, which may extend into surrounding brain tissue undetected by standard imaging, poses a significant challenge. Whole-brain MRSI has been shown to predict relapse sites post-radiotherapy, enhancing the precision of treatment planning [ 2 , 14 ]. The ability of MRSI to detect tumor infiltration more sensitively and precisely than traditional MR imaging allows for more accurate radiation targeting, potentially increasing survival by focusing on both the primary tumor and high-risk recurrence areas.…”

“…A pilot study on MRSI-guided dose escalation demonstrates the advantage of 3D whole-brain MRSI, highlighting its potential to improve glioblastoma management by customizing radiation therapy to each patient’s tumor metabolism. This approach aimed to improve disease management while minimizing radiation exposure to healthy tissue [ 2 , 14 , 15 , 16 ].…”

Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

“…Identifying these areas of restricted diffusion may serve to focus treatment on active tumor tissue. The use of additional information from biological imaging such as [ 18 F]FET (fluoroethyl-l-tyrosine) positron emission tomography/computed tomography (PET/CT) provides a molecular evaluation of malignant abnormalities [11] leading to a more refined analysis of tumoral behavior. A number of studies have proven the clinical value of amino acid tracers, such as [ 18 F]FET PET/CT, to determine the extent of cerebral gliomas for treatment planning [5], the detection of tumor recurrence, and the estimation of prognosis [12][13][14].…”