Abstract

Management of recurrent glioblastoma multiforme (GBM) remains a challenge. Several institutions reported that a single fraction of ≥ 20 Gy for small tumor burden results in excellent local control; however, this is at the expense of a high incidence of radiation necrosis (RN). Therefore, we developed a hypofractionation pattern of 33 Gy/3 fractions, which is a radiobiological equivalent of 20 Gy, with the aim to lower the incidence of RN. We reviewed records of 21 patients with recurrent GBM treated with hypofractionated stereotactic radiation therapy (HFSRT) to their 22 respective lesions. Sixty Gy fractioned external beam radiotherapy was performed as first-line treatment. Median time from primary irradiation to HFSRT was 9.6 months (range: 3.1 – 68.1 months). In HFSRT, a median dose of 33 Gy in 11 Gy fractions was delivered to the 80% isodose line that encompassed the target volume. The median tumor volume was 1.07 cm3 (range: 0.11 – 16.64 cm3). The median follow-up time after HFSRT was 9.3 months (range: 1.7 – 33.6 months). Twenty-one of 23 lesions treated (91.3%) achieved local control while 2/23 (8.7%) progressed. Median time to progression outside of the treated site was 5.2 months (range: 2.2 – 9.6 months). Progression was treated with salvage chemotherapy. Five of 21 patients (23.8%) were alive at the end of this follow-up; two patients remain disease-free. The remaining 16/21 patients (76.2%) died of disease. Treatment was well tolerated by all patients with no acute CTC/RTOG > Grade 2. There was 0% incidence of RN. A prospective trial will be underway to validate these promising results.

Highlights

  • Glioblastoma multiforme (GBM) is the most common primary brain malignant tumor in adults, with 22,850 new cases predicted in 2015 in the US [1]

  • Several institutions reported that a single fraction of ≥ 20 GBM Radiotherapy Median dose (Gy) for small tumor burden results in excellent local control; this is at the expense of a high incidence of radiation necrosis (RN)

  • Tumor recurrence was confirmed on biopsy in 14 patients; in the other seven patients, recurrence was confirmed by diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) mapping and brain positron emission tomography (PET)

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Summary

Introduction

Glioblastoma multiforme (GBM) is the most common primary brain malignant tumor in adults, with 22,850 new cases predicted in 2015 in the US [1]. Surgical resection alone results in a median survival of six months, which can be extended to 14.6 months with aggressive. Minkowitz S, et al (March 17, 2016) Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control with No Radiation Necrosis: Promising Results in the Management of Patients with Small Recurrent Inoperable GBM. A higher radiation dose leads to increased survival [3]; conventionally fractionated doses of 2.0 Gy per fraction greater than a 60 Gy total dose provide no additional benefit while incurring a substantial increase in adverse effects [45]. As a diffusely infiltrative disease, local recurrence remains the most common form of failure pattern after standard treatment [6,7]

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