Accelerated intensity-modulated radiotherapy plus temozolomide in patients with glioblastoma: a phase I dose-escalation study (ISIDE-BT-1).
BACKGROUND
We performed a dose-escalation trial to determine the maximum tolerated dose (MTD) of intensity-modulated radiotherapy (IMRT) with standard concurrent and sequential-dose temozolomide (TMZ) in patients with glioblastoma multiforme.


METHODS
Histologically proven glioblastoma patients underwent IMRT dose escalation. IMRT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed plus the enhancing lesion with 10-mm margin; CTV2 was the area of perifocal edema with 20-mm margin. Only the PTV1 dose was escalated (planned dose escalation: 60, 62.5, 65, 67.5, 70 Gy) while the PTV2 dose remained the same (45 Gy).


RESULTS
Forty consecutive glioblastoma patients were treated. While no dose-limiting toxicity (DLT) was recorded during the dose escalation up to 67.5/2.7 Gy, two out of the first six consecutively enrolled patients on the highest dose level (70/2.8 Gy) experienced a DLT, and therefore a cohort expansion was required. 3/14 patients experienced a DLT on the highest planned dose level, and therefore the MTD was not exceeded. After a median follow-up time of 25 months no grade >2 late neurological toxicity was recorded.


CONCLUSIONS
By using a SIB IMRT technique, a radiation dose of 70 Gy in 25 fractions (biological effective dose--BED--of 92.8 Gy) can be delivered with concurrent and sequential standard dose TMZ, without unacceptable acute toxicity in patients with glioblastoma.
Radiotherapy Unit, Department of Oncology, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy.
Mariangela
M
Massaccesi
Marica
M
Ferro
Savino
S
Cilla
Mario
M
Balducci
Francesco
F
Deodato
Gabriella
G
Macchia
Vincenzo
V
Valentini
Alessio G
AG
Morganti
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D050397:Radiotherapy, Intensity-Modulated; D000077204:Temozolomide
D003606:Dacarbazine; D000077204:Temozolomide