skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

Abstract

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dose delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in allmore » fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

Authors:
 [1];  [1];  [2]; ;  [1]
  1. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)
  2. Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States)
Publication Date:
OSTI Identifier:
22648721
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 3; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRAIN; FRACTIONATED IRRADIATION; MALFORMATIONS; PHOTON BEAMS; RADIATION DOSE DISTRIBUTIONS

Citation Formats

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu, Bussière, Marc R., Chapman, Paul H., Loeffler, Jay S., and Shih, Helen A. Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.02.001.
Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu, Bussière, Marc R., Chapman, Paul H., Loeffler, Jay S., & Shih, Helen A. Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations. United States. doi:10.1016/J.IJROBP.2016.02.001.
Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu, Bussière, Marc R., Chapman, Paul H., Loeffler, Jay S., and Shih, Helen A. 2016. "Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations". United States. doi:10.1016/J.IJROBP.2016.02.001.
@article{osti_22648721,
title = {Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations},
author = {Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu and Bussière, Marc R. and Chapman, Paul H. and Loeffler, Jay S. and Shih, Helen A.},
abstractNote = {Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dose delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.},
doi = {10.1016/J.IJROBP.2016.02.001},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 95,
place = {United States},
year = 2016,
month = 7
}
  • The treatment of large cerebral arteriovenous malformations is a surgical challenge, especially for deep seated brain locations. Furthermore, these lesions are unfit for radiosurgical approaches due to a high risk of complications secondary to high radiation doses to large brain volumes. Fractionated precision radiotherapy can potentially deliver high, uniform, target-contoured dose distributions optimizing the dose reduction to the critical surrounding brain. The results of a study are presented in such a way that dose distributions achievable with proton beams are compared to those with 10 MV x-rays; and the potential improvements with protons evaluated, relying heavily on dose-volume histograms tomore » examine the coverage of the lesion as well as the dose to the normal brain, brain-stem, and optic chiasm.« less
  • Purpose: We investigate retrospectively clinical outcome after radiosurgery (RS) or hypofractionated stereotactic radiotherapy (HSRT) in patients with large cerebral arteriovenous malformations (AVMs). Methods and Materials: This analysis is based on 48 patients with cerebral AVM greater than 4 cm treated with HSRT or RS at our institution. Fifteen patients received HSRT, with 26 Gy median total dose in 4 to 5 fractions, and 33 patients received RS with 17 Gy median total dose in 4 to 5 fractions. Median target volume was 27 cc in HSRT and 7 cc in RS; median maximum diameter was 6 cm and 5 cm,more » respectively. Seventeen patients experienced intracranial hemorrhage before treatment. Median follow-up was 2.6 years. Results: The 3-year and 4-year actuarial complete obliteration (CO) after HSRT was 17% and 33% and after RS was 47% and 60%, respectively. Actuarial CO was higher in AVMs less than 5 cm (66% vs. 37% after 4 years). Intracranial hemorrhage after HSRT occurred in 3 of 15 patients after 18 months median, and after RS in 7 of 33 patients after 17 months median. Bleeding risk was significantly higher in patients with prior hemorrhage (p < 0.04). Preexisting neurologic dysfunction improved/dissolved in 50% and remained stable in 45%. Conclusions: Large AVMs need a long time period to obliterate and show a high bleeding risk. Multimodal treatment strategies are required to reduce treatment volume before radiotherapy.« less
  • Embolization of a portion of the nidus of an arteriovenous malformation not only may alter hemodynamics within the nidus, but also may change blood flow dynamics in adjacent normal vessels. Sequential acetazolamide-challenge xenon CT cerebral blood flow studies were performed in eight patients before and after embolization of arteriovenous malformations to assess the hemodynamic effects on the major vascular territories supplying the malformation. Acetazolamide is a potent cerebral vasodilator, and its administration combined with cerebral blood flow studies allows assessment of cerebral vasoreactivity. In seven of the eight patients, one or more parenchymal areas exhibited a normal cerebral blood flowmore » augmentation response to acetazolamide before embolization, but diminished acetazolamide flow augmentation was seen after embolization, indicating abnormal vasoreactivity. We found that the decrease in vasoreactivity peaked 6-10 days after embolization. In one of the eight patients, a temporary delayed neurologic deficit developed during a period of impaired cerebral vasoreactivity following embolization. Our results suggest that embolization of an arteriovenous malformation can induce vasoreactivity changes in adjacent normal vessels. Because these changes appear to be somewhat time-dependent, an appropriate interval should be observed between embolization stages or before surgical resection of an arteriovenous malformation following embolization to allow hemodynamic equilibration to occur. Acetazolamide challenge combined with serial cerebral blood flow studies following embolization enables determination of this hemodynamic equilibration.« less
  • To determine whether there is a physiologic explanation for the predisposition of patients with certain angiographic characteristics to symptoms of hemorrhage and steal. Superselective transcatheter feeding arterial pressure and mean arterial pressure measurements were obtained before embolotherapy in 32 patients with cerebral arteriovenous malformations. Pressures were correlated with previously described angioarchitectural characteristics predisposing to hemorrhage and steal. These included size of the arteriovenous malformation, feeding artery length, venous drainage pattern, and angiomatous change. The feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios were significantly decreased in patients with angiomatous change. Feeding arterial pressure and feeding arterial pressure/mean arterialmore » pressure ratios progressively decreased as lesions went from peripheral, to mixed, to central venous drainage. A trend for lower feeding arterial pressure was also demonstrated with greater feeding pedicle length. A statistically significant correlation could not be demonstrated between feeding arterial pressure or feeding arterial pressure/mean arterial pressure ratios and size of the arteriovenous malformation, hemorrhage, or symptoms of steal. Feeding arterial pressure measurements help provide a physiologic basis for the relationship between certain angiographic characteristics and hemorrhage and steal symptoms in patients with arteriovenous malformation. 27 refs., 1 fig.« less