Palliative Radiation Therapy for Brain Metastases

Central nervous system (CNS) involvement by tumoral metastasis is a potentially life-threatening complication, representing the immediate cause of death in more than 50 percent of the cases. Of note, brain metastasis represents the most common brain tumor in the United States (US). The most common brain metastasizing tumors include primaries from the lungs, breast, colon, skin (melanoma), and kidney. Two-year and five-year survival rates of 8.1 percent and 2.4 percent are noted for those with intracranial metastasis across various tumor types. Moreover, it has been estimated that 10-40 percent of all patients with cancer will eventually develop brain metastasis. The lack of reporting of the extent of metastatic spread at the time of enrolment into studies and follow-up in advanced cancer patients (who might go onto develop intracranial metastasis later) might be the reason underlying the underdiagnosis of this disease entity. The most common spread route is through the hematogenous route with the seeding of the brain tissue (microvasculature). Interactions between the tumor and the microvascular niche, a neuroinflammatory cascade that aids the spread of tumor and neovascularization, have been postulated to underlie the primary tumor's spread. Intertumoral heterogeneity within the metastatic deposits and a failure to fully understand the clonally selected molecular aberrations might underlie the consistently poor prognosis associated with the tumor's spread to the CNS. The brain ecosystem represents a unique microenvironment with the inherent ability to aid and limit tumor homing in equal measures. While the microvasculature promotes the spread of tumors, penetration of systemic therapies to the brain tissue is limited. Understanding the various mechanisms predisposing to the homing of the tumor cells to the brain and basic knowledge of genetic alterations is necessary for planning optimum treatment. Radiation therapy aims to mitigate the adverse impact of intracranial metastasis on survival and improve the health-related quality of life (HRQoL). Recent research in the management of brain metastasis has focused upon using targeted therapies that have good local bioavailability, strategies to provide conformal radiation, limiting adverse effects of irradiation on neurocognitive, and outlining relevant indications for optimum use of immunotherapy. Local therapy choice depends upon various parameters, namely patient factors (performance status, stage, and estimated survival), tumor factors (location of metastasis, type of tumor, number, size, and extracranial disease status), and prior treatment history. The first evidence of the utility of whole-brain radiotherapy (WBRT) in palliation of brain metastasis came from Chao et al. Their paper was also significant for reporting a high incidence of recurrence in irradiated patients. Subsequent studies by Borgelt et al. were designed to explore the equivalence between different dose fractionation regimens. Both a dose fractionation schedule of 30 Gray in 10 fractions and 37.5 Gray in 15 fractions were equally effective. This chapter aims to recall, analyze, and select appropriate indications and contraindications for the use of palliative radiotherapy in patients with intracranial metastasis. The clinical significance, technique involved, and recent advances in providing palliative radiotherapy in this clinical setting are also addressed.