title: Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.
abstract: OBJECTIVE
  Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue.
  
  
  METHODS
  In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores.
  
  
  RESULTS
  Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires.
  
  
  CONCLUSIONS
  Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.
authors.affiliation: Department of Radiation Oncology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany. mpiroth@ukaachen.de
authors.forename: M D
authors.initials: MD
authors.lastname: Piroth
authors.forename: M
authors.initials: M
authors.lastname: Pinkawa
authors.forename: R
authors.initials: R
authors.lastname: Holy
authors.forename: J
authors.initials: J
authors.lastname: Klotz
authors.forename: S
authors.initials: S
authors.lastname: Schaar
authors.forename: G
authors.initials: G
authors.lastname: Stoffels
authors.forename: N
authors.initials: N
authors.lastname: Galldiks
authors.forename: H H
authors.initials: HH
authors.lastname: Coenen
authors.forename: H J
authors.initials: HJ
authors.lastname: Kaiser
authors.forename: K J
authors.initials: KJ
authors.lastname: Langen
authors.forename: M J
authors.initials: MJ
authors.lastname: Eble
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000528:radiation effects; D059186:Chemoradiotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D011788:Quality of Life; D011832:Radiation Injuries / Q000209:etiology; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D014443:Tyrosine