THER-08. BRAIN METASTASES AS A FIRST SITE OF RECURRENCE IN PATIENTS RECEIVING CHEMOTHERAPY WITH CONTROLLED SYSTEMIC CANCER: A CRITICAL BUT UNDER-RECOGNIZED CLINICAL SCENARIO

BACKGROUND: As the treatment of non-central nervous system (CNS) malignancies has improved, brain metastases (BM) have been observed as a site of first recurrence in patients with controlled or responding systemic cancers. This suggests that while chemotherapy is effective for the systemic disease, drug concentrations in the CNS are likely subtherapeutic. These findings are in accord with data suggesting that over 98% of FDA-approved drugs are unable to penetrate the blood brain barrier (BBB). METHODS: A literature review was conducted to estimate the proportion of patients with non-small lung cancer (NSCLC), breast cancer, and melanoma with controlled systemic cancers who developed BM as initial site of recurrence. Only studies explicitly reporting BM with controlled extra-cranial (EC) disease or reporting the first site of recurrence after chemotherapy were included. RESULTS: Of 262 studies screened,13 contained adequate data regarding the status of systemic cancer and initial site of recurrence. These reported on 1,024 patients. Four studies in patients with NSCLC revealed that 11–43% developed BM as initial site of recurrence. Similar data was seen in patients with breast cancer (6 studies, 4–19%) and metastatic melanoma (3 studies, 4–25%). Approximately 15% of patients on chemotherapy with stable or responding systemic NSCLC, breast cancer, and melanoma developed isolated BM as initial site of relapse. CONCLUSIONS: This literature review included 1,024 patients with common and treatable metastatic cancers whose disease was controlled with chemotherapy. First recurrence in the brain was noted in 23% of those with NSCLC, 12% with breast cancer, and 12% with melanoma. These findings strongly suggest that, while systemic antineoplastic therapy controlled their systemic cancer, concentration of these drugs within the CNS was low, allowing disease progression in the CNS. Reducing the incidence of BM requires novel therapeutic approaches designed to facilitate drug entry through an intact BBB early in treatment.