Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma.
OBJECTIVE
To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM).


METHODS
All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m(2)/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m(2)/day for 5 days every 28 days. Overall and progression-free survivals were evaluated.


RESULTS
No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors.


CONCLUSIONS
Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan. Electronic address: tiuchi@chiba-c.jp.
Toshihiko
T
Iuchi
Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan.
Kazuo
K
Hatano
Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan.
Takashi
T
Kodama
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan.
Tsukasa
T
Sakaida
Division of Gene Diagnosis, Chiba Cancer Center, Chiba, Japan.
Sana
S
Yokoi
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan.
Koichiro
K
Kawasaki
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan.
Yuzo
Y
Hasegawa
Division of Radiation Oncology, Chiba Cancer Center, Chiba, Japan.
Ryusuke
R
Hara
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000401:mortality / Q000473:pathology; D018365:Neoplasm, Residual; D011446:Prospective Studies; D011832:Radiation Injuries / Q000401:mortality / Q000473:pathology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide