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Clinical Trial
. 2024 Jan 5;26(1):153-163.
doi: 10.1093/neuonc/noad119.

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

Anne Laprie  1 , Georges Noel  2 , Leonor Chaltiel  3 , Gilles Truc  4 , Marie-Pierre Sunyach  5 , Marie Charissoux  6 , Nicolas Magne  7 , Pierre Auberdiac  8 , Julian Biau  9 , Soléakhéna Ken  10 , Fatima Tensaouti  11 , Jonathan Khalifa  3 , Ingrid Sidibe  12 , Franck-Emmanuel Roux  13 , Laure Vieillevigne  3 , Isabelle Catalaa  14 , Sergio Boetto  14 , Emmanuelle Uro-Coste  15 , Stéphane Supiot  16 , Valérie Bernier  17 , Thomas Filleron  3 , Muriel Mounier  3 , Muriel Poublanc  3 , Pascale Olivier  18 , Jean-Pierre Delord  3 , Elizabeth Cohen-Jonathan-Moyal  10
Affiliations
Clinical Trial

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

Anne Laprie et al. Neuro Oncol. .

Abstract

Background: 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.

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% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [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% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [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.

Trial registration: NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&rank=1.

Keywords: 3D magnetic resonance spectroscopic imaging; clinical trial; glioblastoma; phase III; radiotherapy.

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Figures

Figure 1.
Figure 1.
CONSORT trial flow diagram. * Two patients, that were included and randomized before checking the quality of the MRI/MRS, had inadequate acquisitions. The MRI/MRS was not repeated in these 2 cases. The 2 patients, included in the HD arm, were treated in the SD arm but analyzed as part of the intention-to-treat in the HD arm.
Figure 2.
Figure 2.
Overall survival and progression-free survival by arm. HD, high dose; OS, overall survival; SD, standard dose.
Figure 3.
Figure 3.
Overall survival by arm and methylation status: (A): methylated; (B): unmethylated; HD, high dose; OS, overall survival; SD, standard dose.
Figure 4.
Figure 4.
Overall survival in patients with pseudoprogression by trial arm (A). Overall survival in patients without pseudoprogression by trial arm (B).
See this image and copyright information in PMC

Comment in

References

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