title: Concurrent temozolomide and dose-escalated intensity-modulated radiation therapy in newly diagnosed glioblastoma.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of (11)C methionine PET (MET-PET) imaging in predicting recurrence.
  
  
  METHODS
  Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m(2)) followed by adjuvant cyclic temozolomide (200 mg/m(2) d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure.
  
  
  RESULTS
  A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0-32.5) and 9.0 (6.0-11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001).
  
  
  CONCLUSIONS
  Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions.
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA. ctsien@umich.edu
authors: Christina I
authors: CI
authors: Tsien
authors: Doris
authors: D
authors: Brown
authors: Daniel
authors: D
authors: Normolle
authors: Matthew
authors: M
authors: Schipper
authors: Morand
authors: M
authors: Piert
authors: Larry
authors: L
authors: Junck
authors: Jason
authors: J
authors: Heth
authors: Diana
authors: D
authors: Gomez-Hassan
authors: Randall K
authors: RK
authors: Ten Haken
authors: Thomas
authors: T
authors: Chenevert
authors: Yue
authors: Y
authors: Cao
authors: Theodore
authors: T
authors: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008715:Methionine / Q000493:pharmacokinetics; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050397:Radiotherapy, Intensity-Modulated; D016879:Salvage Therapy; D015996:Survival Rate; D000077204:Temozolomide; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019275:Radiopharmaceuticals; C086242:carbon-11 methionine; D003606:Dacarbazine; D008715:Methionine; D000077204:Temozolomide