Brain Metastases as a First Site of Recurrence in Patients Receiving Chemotherapy with Controlled Systemic Cancer: a Critical but Under-Recognized Clinical Scenario

Purpose of review: As the treatment of many malignancies has improved, brain metastases (BM) have been observed as a site of the first recurrence in patients with controlled systemic cancers. This suggests that while the administered chemotherapy is effective against systemic cancer, drug concentrations in the central nervous system (CNS) are likely too low to be effective. These findings are in accord with data suggesting that more than 98% of FDA-approved drugs on the market today are unable to cross the blood-brain barrier (BBB). Recent findings: This retrospective literature review was conducted to estimate the proportion of patients with non-small lung cancer, breast cancer, and melanoma who develop BM as their initial site of recurrence while their systemic cancers are well controlled. Of 267 studies screened, 12 studies fit criteria for inclusion. These 12 studies reported on 923 patients. According to compiled data across these studies, 16% of patients on chemotherapy with stable or responding systemic cancer developed isolated BM as their initial site of relapse. Summary: These findings strongly suggest that while chemotherapy controlled systemic cancer, drug concentrations within the CNS were low enough to allow disease progression. Ultimately, reducing the incidence of BM in these patients will require novel therapeutic approaches that facilitate drug entry through an intact BBB early in their treatment.