title: The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial.
abstract: OBJECTIVE
  Despite major advances in treatment modalities, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. Exploring hypofractionated regimens to replace the standard 6-week radiotherapy schedule is an attractive strategy as an attempt to prevent accelerated tumor cell repopulation. There is equally interest in dose escalation to the gross tumor volume where the majority of failures occur. We report our preliminary results using hypofractionated intensity-modulated accelerated radiotherapy regimen in the treatment of patients with GBM.
  
  
  METHODS
  Between July 1998 and December 2001, 25 patients with histologically proven diagnosis of GBM, Karnofsky performance status > or =60, and a postoperative tumor volume < or =110 cm3 were treated with a hypofractionated accelerated course of radiotherapy. The gross tumor volume (GTV) was defined as the contrast-enhancing lesion on the postoperative MRI T1-weighted images with the latter fused with computed tomography images for treatment planning. The planning target volume was defined as GTV + 1.5-cm margin. Using forward-planning intensity modulation (step-and-shoot technique), 60 Gy in 20 daily fractions of 3 Gy each were given to the GTV, whereas the planning target volume received a minimum of 40 Gy in 20 fractions of 2 Gy each at its periphery. Treatments were delivered over a 4-week period using 5 daily fractions per week. Dose was prescribed at the isocenter (ICRU point). Three beam angles were used in all of the cases.
  
  
  RESULTS
  Treatments were well tolerated. Acute toxicity was limited to increased brain edema during radiotherapy in 2 patients who were on tapering doses of corticosteroids. This was corrected by increasing the steroid dose. At a median follow-up of 8.8 months, no late toxicity was observed. One patient experienced visual loss at 9 months after completion of treatment. MRI suggested nonspecific changes to the optic chiasm. On review of the treatment plan, the total dose to the optic chiasm was confirmed to be equal to or less than 40 Gy in 20 fractions. When Radiation Therapy Oncology Group recursive partitioning analysis was used, 10 patients were class III-IV, and 15 patients were class V-VI. To date, 21 patients have had clinical and/or radiologic evidence of disease progression, and 16 patients have died. The median survival was 9.5 months (range: 2.8-22.9 months), the 1-year survival rate was 40%, and the median progression-free survival was 5.2 months (range: 1.9-12.8 months).
  
  
  CONCLUSIONS
  This hypofractionated accelerated irradiation schedule using forward planning (step-and-shoot) hypofractionated, intensity-modulated accelerated radiotherapy is feasible and seems to be a safe treatment for patients with GBM. A 2-week reduction in the treatment time may be of valuable benefit for this group of patients. However, despite this accelerated regimen, no survival advantage has been observed.
authors.affiliation: Department of Oncology, Division of Radiation Oncology, McGill University, Montréal, Quebec, Canada. ksultane@roc.jgh.mcgill.ca
authors.forename: Khalil
authors.initials: K
authors.lastname: Sultanem
authors.forename: Horacio
authors.initials: H
authors.lastname: Patrocinio
authors.forename: Christine
authors.initials: C
authors.lastname: Lambert
authors.forename: Robert
authors.initials: R
authors.lastname: Corns
authors.forename: Richard
authors.initials: R
authors.lastname: Leblanc
authors.forename: William
authors.initials: W
authors.lastname: Parker
authors.forename: George
authors.initials: G
authors.lastname: Shenouda
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001932:Brain Neoplasms / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*