Whitney B. Pope
We published the first paper on bevacizumab-treated glioma over a decade ago and have since seen bevacizumab become an increasingly common, though controversial (as it does not seem to prolong survival), treatment for patients with glioma and other brain tumors. Given the large number of bevacizumab-treated patients in our neuro-oncology clinic, it was not long before we noticed that many patients developed an interesting pattern of periventricular persistent diffusion restriction that did not seem to be associated with infarct, given the extended time course of the abnormality. Thus, we considered the possibility that the diffusion changes could be due to highly cellular tumor, but the apparent diffusion coefficient values of affected regions tended to be very low, and perfusion and PET scans were often “cold” in these areas. Therefore, we analyzed the relationship between persistent diffusion restriction and outcome and found that patients with persistent diffusion restriction lived longer than those without. Furthermore, when several patients had these lesions resected, the histopathology was described as gelatinous or coagulative necrosis.
After publication of our findings, we received quite a lot of positive feedback from other neuroradiologists who had noticed a similar pattern, and several confirmatory studies were subsequently published. Thus, we concluded that this finding may represent an unusual form of necrotic treatment effect found mostly in patients treated with chemoradiation therapy followed by bevacizumab. Interestingly, a group at the Medical College of Wisconsin recently reported that only patients lacking O6-methylguanine-DNA-methyltransferase methylation develop persistent diffusion restriction. These are patients who are typically insensitive to temozolomide treatment (the standard chemotherapeutic for high-grade glioma). Thus, it appears that persistent restricted diffusion may be a manifestation of radiation necrosis in the setting of bevacizumab therapy; and indeed, we witnessed periventricular persistent diffusion restriction in a patient with a brain metastasis who was treated with bevacizumab following development of radiation necrosis.