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Author Clarke, Jennifer ♦ Neil, Elizabeth ♦ Terziev, Robert ♦ Gutin, Philip ♦ Barani, Igor ♦ Kaley, Thomas ♦ Lassman, Andrew B. ♦ Chan, Timothy A. ♦ Yamada, Josh ♦ DeAngelis, Lisa ♦ Ballangrud, Ase ♦ Young, Robert ♦ Panageas, Katherine S. ♦ Beal, Kathryn ♦ Omuro, Antonio
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword RADIOLOGY AND NUCLEAR MEDICINE ♦ ASTROCYTOMAS ♦ FRACTIONATED IRRADIATION ♦ GY RANGE 01-10 ♦ RADIATION DOSES ♦ TOXICITY
Abstract Purpose: To establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas. Methods and Materials: Patients with recurrent high-grade glioma with Karnofsky performance status ≥60, history of standard fractionated initial radiation, tumor volume at recurrence ≤40 cm{sup 3}, and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 phase 1 dose escalation trial design was utilized, with dose-limiting toxicities defined as any grade 3 to 5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10 mg/kg every 2 weeks. Hypofractionated stereotactic reirradiation was initiated after 2 bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy per fraction. Results: A total of 3 patients were enrolled at the 9 Gy × 3 dose level cohort, 5 in the 10 Gy × 3 cohort, and 7 in the 11 Gy × 3 cohort. One dose-limiting toxicity of grade 3 fatigue and cognitive deterioration possibly related to hypofractionated stereotactic reirradiation was observed in the 11 Gy × 3 cohort, and this dose was declared the maximum tolerated dose in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival was 13 months. Conclusions: Reirradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11 Gy × 3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison with our previous 6 Gy × 5 schedule. Promising overall survival warrants further investigation.
ISSN 03603016
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-11-15
Publisher Place United States
Journal International Journal of Radiation Oncology, Biology and Physics
Volume Number 99
Issue Number 4


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