8 Chapter 1 Brain metastases (BMs) are a significant neurological consequence of cancer that occurs when cancer cells from a solid tumor elsewhere in the body migrate to the brain. The most common primary tumors that metastasize to the brain are lung, breast, and melanoma.1 BMs affect a substantial proportion of adult patients with cancer with estimates ranging from 10 to 30%.2–4 Despite improvements in medical treatments, the median overall survival of patients remains limited, ranging from 3 to 47 months.5,6 Various factors influence survival, including age, Karnofsky performance status (KPS), extent of extracranial disease, number of BMs, and histological and molecular features of the primary tumor.5–9 Currently, treatment options for BMs include surgery, chemotherapy, immunotherapy, and radiotherapy, typically given in a combination. The population of patients with BMs is expected to grow in the coming years due to advancements in medical treatments improving survival of cancer patients and enhanced imaging techniques allowing for earlier detection of BMs.10–12 Consequently, patients with BMs are now living longer with cancer. In this context, patient-centered treatment is increasingly focused on not only extending the life span, but especially on maintaining or even improving quality of life (QoL). RADIOTHERAPY FOR BRAIN METASTASES Radiotherapy is a cornerstone of medical treatment for BMs. It is a non-invasive technique in which ionizing radiation is delivered to the affected areas. By damaging the DNA within cancerous cells, radiation therapy can lead to senescence and ultimately cell death. The two prominent strategies for radiotherapy in BMs are stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT; Figure 1). Traditionally, WBRT was the standard treatment for BMs. Stereotactic treatment can be delivered using either a gamma knife or a conventional linear accelerator. Both apply a steep dose gradient by allowing overdosage up to 130 percent inside the tumor. Due to advances in these techniques, SRS has now been established as an optimal option for patients with one up to ten BMs, with a total volume of ≤30 cc.13–15 With SRS, the radiation dose to the target is divided over multiple arc beams delivered from different angles to accumulate a high-precision localized dose in the BMs while reducing the dose to the surrounding healthy brain tissue. The prescribed physical dose to the BMs usually varies between 15 and 24 Gray (Gy), dependent on the size of the lesion. WBRT is typically advised to patients with more than ten BMs to ensure coverage of all brain tissue and to sterilize not-yet visible BMs.16,17 WBRT is either delivered in five fractions of 4 Gy or ten fractions of 3 Gy: a much lower biological dose to prevent immediate whole brain damage. To decrease radiation
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