Radiation Induced Cerebral Microbleeds in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy

Purpose Proton beam radiotherapy (PBT) has been increasingly utilized to treat pediatric brain tumors, however, limited information exists regarding radiation induced cerebral microbleeds (CMBs) among these patients. The purpose was to evaluate the incidence, risk factors, and imaging appearance of CMBs in pediatric patients with brain tumors treated with PBT. Methods A retrospective study was performed on 100 pediatric patients with primary brain tumors treated with PBT. CMBs were diagnosed by examining serial MRIs including susceptibility-weighted imaging. Radiation therapy plans were analyzed to determine doses to individual CMBs. Clinical records were used to determine risk factors associated with the development of CMBs in these patients. Results The mean age at time of PBT was 8.1 years. The median follow-up duration was 57 months. The median time to development of CMBs was 8 months (mean 11 months; range 3-28 months). The percentage of patients with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1-year, 2-years, 3-years, 4-year, 5-years, and greater than 5 years from completion of proton radiotherapy. The majority (87%) of CMBs were found in areas of brain exposed to ≥ 30 Gy. Risk factors included maximum radiotherapy dose (P=0.001), percentage and volume of brain exposed to ≥ 30 Gy (P=0.0004; P=0.0005), and patient age at time of PBT (P=0.0004). Chemotherapy was not a significant risk factor (P=0.35). No CMBs required surgical intervention. Conclusion CMBs develop in a high percentage of pediatric patients with brain tumors treated with proton radiotherapy within the first few years following treatment. Significant risk factors for development of CMBs include younger age at time of PBT, higher maximum radiotherapy dose, and higher percentage and volume of brain exposed to ≥ 30 Gy. These findings demonstrate similarities with CMBs that develop in pediatric brain tumor patients treated with photon radiotherapy