How upfront can we be about upfront therapy for brain metastases in patients with activating epidermal growth factor receptor mutation?

Molecular-targeted therapy has already changed the paradigm of cancer therapy. Among many molecular-targeted therapeutic agents, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have significantly improved the outcomes of lung cancer patients with EGFR activating mutations and become the standard therapy as first-line or front-line therapy for them. On the other hand, advance in high-technology radiotherapy, such as stereotactic radiosurgery (SRS), has dramatically improved our capability of local control of small tumors with reduction in toxicity compared to conventional radiotherapy. Owing to the advances, we sometimes have to face a big dilemma when choosing front-line therapy for patient with both activating EGFR mutation and brain metastasis simultaneously. To make matter worse, as more sensitive brain imaging or magnetic resonance imaging (MRI) of the brain has already become a routine staging scan in advanced or metastatic non-small cell lung cancer (NSCLC), we see metastatic brain tumors more often than before and most of them are very small or asymptomatic.