CN-20BEVACIZUMAB CAUSING RECURRENT CEREBRAL INFARCTION IN A PATIENT WITH GLIOBLASTOMA: A PREVIOUSLY UNDOCUMENTED PHENOMENON

摘要

BACKGROUND: Bevacizumab, an anti-angiogenic VEGF antibody, is utilized for various malignancies, including glioblastoma multiforme (GBM). There has long been a correlation between bevacizumab therapy and CNS complications, including ischemic stroke and intracranial hemorrhage. Data on the pathophysiology of this correlation are scarce, and it has proven difficult to ascribe causality. To our knowledge there has never been a documented case of recurrent ischemia temporally associated with recurrent bevacizumab therapy. RESULTS: SS is a 70 year-old man with GBM. He received concomitant radiation and temozolamide (TMZ), followed by adjuvant TMZ and bevacizumab. After 5 cycles of TMZ/bevacizumab, he developed acute-onset left hemiparesis, upon which an MRI demonstrated an acute ischemic infarction. Angiography demonstrated mild attenuation of distal branches within the tumor bed. Chemotherapy was temporarily suspended, but after nearly two months, he had clinically recovered somewhat from the infarction. His TMZ/bevacizumab was restarted as his MRIs had been favorable to that point, with little disease progression. However, shortly thereafter, he had acute recurrence of his hemiparesis, and MRI again demonstrated acutely restricted diffusion. He was therefore switched to an alternative regimen that did not include bevacizumab. CONCLUSIONS: Here we describe a case of an ischemic stroke with radiographic correlate while on bevacizumab, with clinical improvement arrested by the development of a recurrent stroke when bevacizumab was restarted. Interestingly, the distal arteries within the stroke bed appeared somewhat attentuated, suggestive of radiation vasculopathy. This case, describing a previously undocumented phenomenon, raises the possibility of a synergistic effect of bevacizumab and radiation vasculopathy. It may be that radiation vasculoapthy alone is typically insufficient to cause ischemia, but the addition of bevacizumab may precipitate a sufficiently anti-vascular milieu as to cause frank and sudden-onset ischemia. In implicating bevacizumab, future directions may include large-scale studies to explore the temporal association of bevacizumab and ischemic stroke.