A phase I dose escalation study using simultaneous integrated-boost IMRT with temozolomide in patients with unifocal glioblastoma

To evaluate the maximum tolerated dose of simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) associated with temozolomide in patients with glioblastoma. Between November 2009 and January 2012, nine patients with malignant glioma were enrolled in this phase I clinical trial. Radiotherapy was delivered using fractions of 2.5Gy on the planning target volume b and of 1.9Gy on the planning target volume a. Volumes were defined as follow: gross tumour volume b: tumour taking up contrast on T1 weighted MRI images; clinical target volume b: gross tumour volume b+0.5cm (adapted to the anatomical structures) and lastly planning target volume b: clinical target volume b+0.5cm; gross tumour volume a: tumour (gross tumour volume b)+2cm and including oedema outlined on T2Flair MRI sequences; clinical target volume a gross tumour volume a+0.5cm (adapted to the anatomical structures); planning target volume a: clinical target volume a+0.5cm. Three patients were enrolled at each of the three levels of dose (70, 75 and 80Gy prescribed on the planning target volume b and 56, 60 and 60.8Gy on the planning target volume a). Radiotherapy was delivered with temozolomide according to the standard protocol. Dose-limiting toxicities were defined as any haematological toxicities at least grade 4 or as any radiotherapy-related non-haematological acute toxicities at least grade 3, according to the Common Terminology Criteria for Adverse Events, version 3.0. Until the last dose level of 80Gy, no patient showed dose-limiting toxicity. SIB-IMRT, at least until a dose of 80Gy in 32 daily fractions, associated with temozolomide is feasible and well tolerated. Évaluer pour des patients atteints d’un glioblastome la dose maximale tolérée de radiothérapie délivrée avec modulation d’intensité avec un boost intégré (SIB-IMRT) en association au témozololomide. Entre novembre 2009 et janvier 2012, neuf patients atteints d’un gliome de grade IV ont été inclus dans cet essai de phase I. La radiothérapie a été administrée par fractions de 2,5Gy dans le volume cible prévisionnel b et de 1,9Gy sur le volume cible prévisionnel a. La définition des volumes était : volume tumoral macroscopique b : tumeur prenant le contraste après injection de gadolinium en séquence T1 ou lit opératoire+prise de contraste ; volume cible anatomoclinique b : volume tumoral macroscopique b+0,5cm (corrigé aux barrières anatomiques) et enfin volume cible prévisionnel b : volume cible anatomoclinique b+0