As radiation is selectively toxic to more rapidly dividing cells, the two normal cell types within the CNS most vulnerable to RN are vascular endothelium (which have a turnover time of ≈ 6–10 mos) and oligodendroglial cells. Vascular injury may be the primary limiting factor to the tolerance of cranial XRT 1). Injury from XRT occurs at lower doses when given concurrently with chemotherapy (especially methotrexate).
The mechanism(s) by which XRT causes side effects is not known with certainty, but may be due to:
1. damage to vascular endothelium: effects on cerebral vasculature may differ substantially from effects on systemic vessels 2).
2. glial injury
3. immune system effect
Radiation effects are divided into 3 phases:
1. acute: occur during treatment. Rare. Usually an exacerbation of symptoms already present. Probably secondary to edema. Treat with ↑ steroids
2. early delayed: few weeks to 2–3 mos following completion of XRT. In spinal cord →Lhermitte’s sign. In brain →post-irradiation lethargy & memory difficulties
3. late delayed: 3 mos-12 yrs (most within 3 years). Due to small artery injury →thrombotic occlusion →white matter atrophy or frank coagulative necrosis.
Radiation induced necrosis in the brain has been treated using bevacizumab.
Perez-Torres et al. validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, they found that VEGF over-expression and radionecrosis developed simultaneously, which precludes preventative anti-VEGF treatment 3).