Glioblastoma is the most common and aggressive adult primary brain cancer. 
Despite multimodal therapy, it is associated with a survival of less than two 
years. Greater than 85% of recurrences occur within the original area of surgery 
and radiotherapy, suggesting a potential for improved local treatments. In 
addition to cancer cell invasion beyond surgical margins, a plethora of 
postinjury pro-proliferative stimuli are released from local healing brain, 
which both protect and nourish remaining cancer cells. This review compiles 
preclinical and clinical evidence for a dedicated treatment of both residual 
cancer cells and regional microenvironment using intraoperative radiotherapy 
(IORT).