Brain metastases life expectancy depends on the primary tumor, underlying biology and systemic therapy. Recent advances in the understanding of molecular pathways that mediate oncogenesis and metastasis have stimulated preclinical and clinical research into novel targeted therapies to reduce the impact of BM. However, the blood-brain barrier still poses obstacles to delivering effective chemotherapeutic agents to BM, and radiotherapy is currently considered the first line treatment for BM. The optimal management of BM aims to achieve local control of the metastatic lesion with minimal side effects, thus maintaining function and preventing neurological decline.
The NHIS database is an extensive medical insurance data source that contains information on diagnosis, drug treatment, other treatment, imaging use, and death in the entire Korean population. In this study, NHIS records from 20-79 years old patients with a newly diagnosed BM were used. A total of 116 BM from solid malignancies were included, with lung cancer representing the most common primary malignancy (68.9%). Patients were stratified by GPA based on diagnosis-specific prognostic indices and updated indices, with robust separation of the groups/score, confirming marked heterogeneity in survival.
RT is currently the standard of care for solitary BM, and patients with multiple BM are referred for surgery or WBRT. For solitary BM, resection is associated with improved survival compared to WBRT alone. Moreover, in a prospective trial, Fotemustine plus ipilimumab demonstrated a superior relapse-free survival compared with standard of care chemotherapy for patients with melanoma with one or more brain metastases, and was associated with improved neurocognitive outcomes.
However, the role of RT is limited by the blood-brain barrier and the risk of radiation-induced toxicity, and therefore, the optimal therapy for patients with BM remains under exploration. The GPA provides an accurate method to estimate survival for BM and should be used in clinical trials to expand eligibility, democratize enrollment and enhance accrual of patients with a broad spectrum of diagnoses, including those with hematological malignancies.
Conventional wisdom has rendered many BM patients ineligible for clinical trials due to the fear that their poor survival would mask the benefit of other promising treatments. However, a GPA-based metric allows patients with BM to be included in studies of all types of systemic therapy, as long as the primary focus is unrelated to their brain metastases. Failure to stratify by the GPA could render those trials uninterpretable and a waste of time and resources.
