Innovative Diagnostic and Therapeutic Approaches for Radiation Necrosis

Radiation necrosis (RN) is a serious complication of stereotactic radiosurgery (SRS), affecting ∼5% to 25% of patients treated for brain metastases. Because RN is a late effect of radiation therapy with a typical onset of 6 to 12 months after treatment, the incidence of RN is expected to rise as advancements in systemic therapy prolong survival among patients with brain metastases. The exact radiobiological mechanisms behind RN are still unclear but likely driven by a self-sustaining feedback loop involving vascular injury, ischemia, neuroinflammation and perivascular fibrosis. Although multiple diagnostic tools are currently used or being investigated to help distinguish RN from tumor progression (TP), including MR perfusion, MR spectroscopy, and Amino Acid PET/CT, the clinical utility of each of these tools is limited by suboptimal specificity, lesion size criteria, limited access and susceptibility to treatment-related factors such as prior bevacizumab. First line management of symptomatic RN is steroids, with escalation to bevacizumab or aggressive, local therapies such as LITT and resection for steroid refractory RN. Refining our understanding of normal brain tissue dose tolerances, characterizing the safety profile of concurrent administration of SRS with different precision systemic therapies and integrating novel risk stratification tools such as the Recursive Partitioning Analysis (RPA) for RN will be key to reducing the risk of RN after SRS. These prevention strategies along with the development of novel therapies informed by enhanced insight into the pathophysiology of RN promise to improve long-term quality of life for patients with brain metastases.