Janine M Lupo1, Annette M Molinaro1, Emma Essock-Burns1, Nicholas Butowski1, Susan M Chang1, Soonmee Cha1, Sarah J Nelson1. 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.
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.
Authors: E Mark Haacke; Norman Y C Cheng; Michael J House; Qiang Liu; Jaladhar Neelavalli; Robert J Ogg; Asadullah Khan; Muhammad Ayaz; Wolff Kirsch; Andre Obenaus Journal: Magn Reson Imaging Date: 2005-01 Impact factor: 2.546
Authors: E M Haacke; Z S DelProposto; S Chaturvedi; V Sehgal; M Tenzer; J Neelavalli; D Kido Journal: AJNR Am J Neuroradiol Date: 2007-02 Impact factor: 3.825
Authors: Rajan Jain; Patricia L Robertson; Dheeraj Gandhi; Sachin K Gujar; Karin M Muraszko; Stephen Gebarski Journal: AJNR Am J Neuroradiol Date: 2005-05 Impact factor: 3.825
Authors: Cassie Kline; Schuyler Stoller; Lennox Byer; David Samuel; Janine M Lupo; Melanie A Morrison; Andreas M Rauschecker; Pierre Nedelec; Walter Faig; Dena B Dubal; Heather J Fullerton; Sabine Mueller Journal: Front Oncol Date: 2022-06-23 Impact factor: 5.738
Authors: Melanie A Morrison; Christopher P Hess; Jennifer L Clarke; Nicholas Butowski; Susan M Chang; Annette M Molinaro; Janine M Lupo Journal: J Magn Reson Imaging Date: 2019-01-20 Impact factor: 4.813
Authors: Sivakami Avadiappan; Melanie A Morrison; Angela Jakary; Erin Felton; Schuyler Stoller; Christopher P Hess; Annette M Molinaro; Steve E Braunstein; Sabine Mueller; Janine M Lupo Journal: J Neurooncol Date: 2021-04-24 Impact factor: 4.130