We thank the authors for their reply to our article. We agree that it is of utmost importance to disentangle the complex determinants of microvasculopathy development as well as the determinants of potential regression in this vulnerable population of pediatric brain tumor patients. We find that their demonstration that radiation-induced cerebral microbleeds (CMBs) can progress to cavernomas to be an important observation. Although this was not a specific end point of our study, we did note that one patient in our cohort had a CMB that developed into a cavernous malformation. We have previously reported that cavernous malformations are common in survivors of pediatric brain tumors who received radiation and can present on a spectrum of histological features.1 It is our goal to continue to follow this cohort of patients to observe the natural history of these lesions.
Regarding the use of bevacizumab, we acknowledge that the population who received this drug may have been unique. However, there was no significant difference in tumor type or rate of tumor recurrence between patients who developed CMBs and those who did not (Table 1).2 Post-hoc analysis of patients who received bevacizumab demonstrates that the rate of recurrence between patients who received bevacizumab and those who did not was not statistically different (36% and 20%, P = .145), though patients with high- or low-grade gliomas were more likely to receive bevacizumab (67% versus less than 10% for all other tumor types, P = .004). Interestingly, others have shown that administration of the anti-angiogenic drug enzastaurin with cranial radiation therapy was associated with decreased rate of additional CMB formation in adults. The underlying etiology for this was hypothesized to be a potential radioprotective effect of the anti-angiogenic therapy on microvasculature by decreasing capillary permeability and cytokine release.3
Determining the role specifically of bevacizumab on CMB development was not the focus of our study, and given that we had only 14 patients who received bevacizumab, more numbers are needed to further study the effect of bevacizumab on CMB development and potential evolution.
References
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