Multicenter, phase 1, dose escalation study of hypofractionated stereotactic radiation therapy with bevacizumab for recurrent glioblastoma and anaplastic astrocytoma Journal Article
| Authors: | Clarke, J.; Neil, E.; Terziev, R.; Gutin, P.; Barani, I.; Kaley, T.; Lassman, A. B.; Chan, T. A.; Yamada, J.; DeAngelis, L.; Ballangrud, A.; Young, R.; Panageas, K. S.; Beal, K.; Omuro, A. |
| Article Title: | Multicenter, phase 1, dose escalation study of hypofractionated stereotactic radiation therapy with bevacizumab for recurrent glioblastoma and anaplastic astrocytoma |
| 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 cm3, 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. © 2017 Elsevier Inc. |
| Keywords: | adult; clinical article; controlled study; middle aged; cancer surgery; overall survival; fatigue; neutropenia; bevacizumab; hypertension; multimodality cancer therapy; cancer patient; nuclear magnetic resonance imaging; glioma; neurosurgery; prospective study; progression free survival; infection; multiple cycle treatment; tumor volume; leukopenia; cohort analysis; radiation injury; necrosis; drug dose escalation; lymphocytopenia; hyponatremia; karnofsky performance status; tumors; radiation dose fractionation; multicenter study; tumor recurrence; glioblastoma; muscle weakness; radiation hazard; maximum tolerated dose; phase 1 clinical trial; mental deterioration; toxicity; stereotactic body radiation therapy; brain ischemia; radiation dose distribution; brain stem; meningitis; radiation necrosis; chemoradiotherapy; skin infection; hypofractionated; corpus callosum; dose limiting toxicity; dose-escalation study; high-grade gliomas; re-irradiation; anaplastic astrocytoma; hypofractionated radiotherapy; methods and materials; intention to treat analysis; human; male; female; priority journal; article; infestation; hypofractionated stereotactic radiation therapy |
| Journal Title: | International Journal of Radiation Oncology, Biology, Physics |
| Volume: | 99 |
| Issue: | 4 |
| ISSN: | 0360-3016 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2017-11-15 |
| Start Page: | 797 |
| End Page: | 804 |
| Language: | English |
| DOI: | 10.1016/j.ijrobp.2017.06.2466 |
| PROVIDER: | scopus |
| PMCID: | PMC5654655 |
| PUBMED: | 28870792 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2017 -- Source: Scopus |
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