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Neuro Oncol. 2016 Jan;18(1):87-95. doi: 10.1093/neuonc/nov128. Epub 2015 Jul 22.

The effects of anti-angiogenic therapy on the formation of radiation-induced microbleeds in normal brain tissue of patients with glioma.

Author information

1
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California (J.M.L., E.E.-B., S.C., S.J.N.); Department of Neurosurgery, University of California San Francisco, San Francisco, California (A.M.M., N.B., S.M.C., S.C.); Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California (A.M.M.); Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California (S.J.N.).

Abstract

BACKGROUND:

Radiotherapy (RT) is an integral component in managing patients with glioma, but the damage it may cause to healthy brain tissue and quality of life is of concern. Susceptibility-weighted imaging (SWI) is highly sensitive to the detection of microbleeds that occur years after RT. This study's goals were to characterize the evolution of radiation-induced microbleeds in normal-appearing brain and determine whether the administration of an anti-angiogenic agent altered this process.

METHODS:

Serial high-resolution SWI was acquired on 17 patients with high-grade glioma between 8 months and 4.5 years posttreatment with RT and adjuvant chemotherapy. Nine of these patients were also treated with the anti-angiogenic agent enzastaurin. Microbleeds were identified as discrete foci of susceptibility not corresponding to vessels, tumor, or postoperative infarct, and counted in normal-appearing brain. Analysis of covariance was performed to compare slopes of regression of individual patients' microbleed counts over time, Wilcoxon rank-sum tests examined significant differences in rates of microbleed formation between groups, and linear and quadratic mixed-effects models were employed.

RESULTS:

The number of microbleeds increased with time for all patients, with initial onset occurring at 8-22 months. No microbleeds disappeared once formed. The average rate of microbleed formation significantly increased after 2 years post-RT (P < .001). Patients receiving anti-angiogenic therapy exhibited fewer microbleeds overall (P < .05) and a significant reduction in initial rate of microbleed appearance (P = .01).

CONCLUSIONS:

We have demonstrated a dramatic increase in microbleed formation after 2 years post-RT that was decelerated by the concomitant administration of anti-angiogenic therapy, which may aid in determining brain regions susceptible to RT.

KEYWORDS:

anti-angiogenic therapy; glioma; microbleeds; radiation therapy; susceptibility-weighted imaging; treatment effects

PMID:
26206774
PMCID:
PMC4677411
DOI:
10.1093/neuonc/nov128
[Indexed for MEDLINE]
Free PMC Article

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