As patients live longer with advanced cancer, brain metastases are now becoming a frequent and even chronic condition managed with a variety of systemic agents and local treatments.1 Radiotherapy plays a key role in treatment of intracranial lesions. Whole brain radiation therapy (WBRT) has the benefit of treating both imaging-apparent and microscopic disease. This approach can offer general intracranial disease control, but can damage healthy brain tissue, resulting in neurocognitive impairment associated with irradiation of the hippocampus.2 The innovation of hippocampal-avoidance WBRT (HA-WBRT) maintains global intracranial disease control while reducing neurocognitive decline relative to traditional WBRT, even in the setting of the neuroprotectant memantine (0.74; 95% CI, 0.58−0.95; P = .02), making HA-WBRT a standard-of-care approach to appropriate patients.3-5 Nevertheless, HA-WBRT requires several weeks of daily treatments and often time off systemic therapy. Conversely, stereotactic radiation (SRT) is given over 1 to 3 treatments to the visible lesions, allowing for higher radiation dose, better focal disease control, and sparing of healthy brain tissue, which further reduces neurocognitive toxic effects. SRT is appropriate for patients with a finite number of visible lesions but may allow microscopic disease elsewhere in the brain to progress, necessitating subsequent treatments or even salvage WBRT. In addition, the higher dose of SRT can cause radiation necrosis and inflammation, requiring steroids or other medical and surgical interventions.4 The optimal balance of intracranial disease control with patient-reported outcomes (PROs) is of increasing importance as patients live longer with the subacute and chronic toxic effects of radiotherapy.
To find that balance, multiple randomized clinical trials have confirmed that SRT offers improved efficacy and PROs compared with WBRT in patients with 1 to 4 brain metastases.2, 6-9 However, with advances in systemic therapy and surveillance, patients now frequently present with multiple brain metastases, high performance status, and expected survival of months to years. Without any high-level evidence comparing the efficacy and toxic effects of HA-WBRT with SRT in patients with 5 or more brain metastases, radiation oncologists have been left to make recommendations between each modality on a case-by-case basis. Shared decision-making attempts to account for lesion number, velocity, distribution, size, histologic findings, symptomatology, available systemic therapeutics with central nervous system penetrance, treatment goals, and tolerance for cognitive decline.