Systematic review of the incidence and risk factors for cerebral vasculopathy and stroke after cranial proton and photon radiation for childhood brain tumors

Abstract

Background: The aim of our study is to determine the incidence, timing, and risk factors for cerebral vasculopathy after cranial proton and photon radiation for pediatric brain tumors.

Methods: We performed a single-institution retrospective review of a cohort of children treated with proton radiation for brain tumors. MRA and/or MRI were reviewed for evidence of cerebral vascular stenosis and infarcts. Twenty-one similar studies (17 photon, 4 proton) were identified by systematic literature review.

Results: For 81 patients with median follow-up of 3 years, the rates of overall and severe vasculopathy were 9.9% and 6.2% respectively, occurring a median of 2 years post radiation. Dose to optic chiasm greater than 45 Gy and suprasellar location were significant risk factors. Results were consistent with 4 prior proton studies (752 patients) that reported incidence of 5% to 6.7%, 1.5 to 3 years post radiation. With significantly longer follow-up (3.7-19 years), 9 studies (1108 patients) with traditional photon radiation reported a higher rate (6.3%-20%) and longer time to vasculopathy (2-28 years). Significant risk factors were neurofibromatosis type 1 (NF-1; rate 7.6%-60%) and suprasellar tumors (9%-20%). In 10 studies with photon radiation (1708 patients), the stroke rate was 2% to 18.8% (2.3-24 years post radiation).

Conclusions: Childhood brain tumor survivors need screening for vasculopathy after cranial radiation, especially with higher dose to optic chiasm, NF-1, and suprasellar tumors. Prospective studies are needed to identify risk groups, and ideal modality and timing, for screening of this toxicity.

Keywords: cerebral vasculopathy; childhood brain tumors; photon radiation; proton radiation; stroke.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Flow Diagram.

Figure 2.

Magnetic Resonance Angiography Images of Grades of Vasculopathy Based on Degree of Cerebral Vascular Narrowing Compared to Normal Proximal Segment. A, Mild vasculopathy with less than 25% narrowing; B, Moderate vasculopathy with 25% to 75% narrowing; C, Severe vasculopathy with greater than 75% narrowing; area of vasculopathy is encircled in white.