title: Long-term survival after treatment of glioblastoma multiforme with hyperfractionated concomitant boost proton beam therapy.
abstract: OBJECTIVE
  Although conventional x-ray therapy of 60 Gy in 30 fractions is generally used in our institute as well as others, the prognosis of patients with glioblastoma multiforme (GBM) is poor. The purpose of this study was to evaluate the characteristics of long-term GBM survivors after postoperative hyperfractionated concomitant boost x-ray radiation therapy and proton beam therapy.
  
  
  METHODS
  Twenty-three of 81 GBM patients who met the eligible criteria and consented to the protocol were treated with x-ray radiation therapy (50.4 Gy in 28 fractions in T2-high areas) and proton beam therapy (46.2 GyE in 28 fractions in gadolinium-enhanced volumes >6 hours after x-ray radiation therapy) concurrent with nimustine hydrochloride or temozolomide.
  
  
  RESULTS
  Treatment was completed in all patients within 38-50 days (median, 43 days). Six currently living patients (median follow-up period, 70.9 months) developed radiation necrosis without tumor recurrence. Of these, 5 underwent necrotomy and 2 received bevacizumab after necrotomy. Compared with the pretreatment status, the Karnofsky performance scale (KPS) for the 6 survivors decreased by 10%-30% at the last follow-up. However, radiation necrosis had been well controlled and 5 of 6 patients maintained a stable KPS without hospital care.
  
  
  CONCLUSIONS
  The results suggest that high-dose proton beam therapy could control GBM pathogenesis if the treatment area completely covers tumor infiltration. Although radiation necrosis was inevitable, the remaining brain volume was fairly well preserved in the long-term survivors.
authors.affiliation: Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizumoto
authors.affiliation: Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Takano
authors.affiliation: Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.affiliation: Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okumura
authors.affiliation: Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Neurosurgery, Osaka Medical Collage, Osaka, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyatake
authors.affiliation: Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; Department of Neurosurgery, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: tsuboi@pmrc.tsukuba.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000627:therapeutic use; D011379:Prognosis; D061766:Proton Therapy / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015376:Nimustine; D003606:Dacarbazine; D000077204:Temozolomide