title: Phase I/II trial of hyperfractionated concomitant boost proton radiotherapy for supratentorial glioblastoma multiforme.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM).
  
  
  METHODS
  Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of >or=60; (2) the diameter of the enhanced area before radiotherapy was <or=40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T(2)-weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks.
  
  
  RESULTS
  Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months.
  
  
  CONCLUSIONS
  Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences.
authors.affiliation: Proton Medical Research Center, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Igaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Takano
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Oshiro
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Haruko
authors.initials: H
authors.lastname: Hashii
authors.forename: Ayae
authors.initials: A
authors.lastname: Kanemoto
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Nakayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Sugahara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.forename: Koichi
authors.initials: K
authors.lastname: Tokuuye
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D003907:Dexamethasone / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects; D011832:Radiation Injuries / Q000188:drug therapy; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D015996:Survival Rate; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D011522:Protons; D015376:Nimustine; D003907:Dexamethasone; D011239:Prednisolone