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

Abstract

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Fig. 1

Radiotherapy Target Volumes. The initial planning target volume (TVi - dotted line) consisted of a 1 cm geometric margin around the gross tumor volume (defined as the T1-weighted MRI enhancing tumor + the resection cavity) and the clinical target volume (defined as edema visible on T2-weighted MRI). The boost planning target volume (TVb - dashed line) consisted of a 0.5 cm geometric margin on the gross tumor volume.

Fig. 2

Overall and progression-free survival. Outcomes for all 21 patients enrolled in the trial are depicted. Median overall survival was 13.6 months and median progression-free survival was 6.5 months.

Fig. 3

Outcomes by radiotherapy dose. Overall (A) and progression-free survival (B) curves for patients by radiotherapy dose are depicted. No significant difference is found in outcomes based on dose group.