A phase I dose escalation study of hypofractionated IMRT field-in-field boost for newly diagnosed glioblastoma multiforme

Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):743-8. doi: 10.1016/j.ijrobp.2010.10.018. Epub 2011 Jan 13.


Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost.

Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy.

Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy.

Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy
  • Otitis Media
  • Prospective Studies
  • Radiation Injuries / complications
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Survival Rate