Evaluation of Potential Predictive Biomarkers for Defining Brain Radiotherapy Efficacy in Non-Small Cell Lung Cancer Patients with Brain Metastases: A Case Report and a Narrative Review.

Non-small cell lung cancer (NSCLC) is the second most common cancer worldwide, resulting in 1.8 million deaths per year. Most patients are diagnosed with a metastatic disease. Brain metastases are one of the most common metastatic sites and are associated with severe neurological symptoms, shorter survival, and the worst clinical outcomes. Brain radiotherapy and systemic oncological therapies are currently used for controlling both cancer progression and neurological symptoms. Brain radiotherapy includes stereotactic brain ablative radiotherapy (SBRT) or whole brain radiotherapy (WBRT). SBRT is applied for single or multiple (up to ten) small (diameter less than 4 cm) lesions, whereas WBRT is usually applied for multiple (more than ten) and large (diameter greater than 4 cm) brain metastases. In both cases, radiotherapy application may be viewed as an overtreatment which causes severe toxicities without achieving a significant clinical benefit. Thus far, a number of scoring systems to define the potential clinical benefits derived from brain radiotherapy have been proposed. However, most are not well established in clinical practice. In this article, we present a clinical case of a patient with advanced NSCLC carrying a BRAF mutation and brain metastases. We review the variables in addition to applicable scoring systems considered to have potential for predicting clinical outcomes and benefits of brain radiotherapy in patients with advanced NSCLC and brain metastases. Lastly, we highlight the unmet need of specific scoring systems for advanced NSCLC patients with brain metastases carrying oncogene alterations including BRAF mutations.