title: Phase I three-dimensional conformal radiation dose escalation study in newly diagnosed glioblastoma: Radiation Therapy Oncology Group Trial 98-03.
abstract: OBJECTIVE
  To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM).
  
  
  METHODS
  A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV(1)), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV(2), defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV(2) <75 cm(3); Group 2: PTV(2) >or=75 cm(3)). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m(2) was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced.
  
  
  RESULTS
  Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade >or=3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months). Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was 8.2-13.9 months.
  
  
  CONCLUSIONS
  Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. ctsien@umich.edu
authors: Christina
authors: C
authors: Tsien
authors: Jennifer
authors: J
authors: Moughan
authors: Jeff M
authors: JM
authors: Michalski
authors: Mark R
authors: MR
authors: Gilbert
authors: James
authors: J
authors: Purdy
authors: Joseph
authors: J
authors: Simpson
authors: John J
authors: JJ
authors: Kresel
authors: Walter J
authors: WJ
authors: Curran
authors: Aidnag
authors: A
authors: Diaz
authors: Minesh P
authors: MP
authors: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009336:Necrosis / Q000473:pathology; D011446:Prospective Studies; D011786:Quality Control; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods / Q000592:standards; D012086:Reoperation; D013256:Steroids / Q000008:administration & dosage; D015173:Supratentorial Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013256:Steroids; D002330:Carmustine