27 Cognitive Impact of SRS vs. WBRT: Systematic Review & Meta-analysis INTRODUCTION Local and systemic treatment for extracranial cancers is improving, leading to longer life expectancy. New challenges arise due to increased survival rates including the development of brain metastases (BMs). BMs occur in at least 10% of patients diagnosed with cancer and this incidence continues to rise.1,2 BMs are difficult to treat systemically because chemotherapeutic agents barely pass the blood-brain barrier. Median overall survival, despite systemic and focal treatment, is limited spanning months to several years, depending on factors such as lesion number, Karnofsky performance status and the primary cancer as reflected in GPA calculators.3,4 Treatment (shared) decisions in this vulnerable patient population are tailored towards gaining the best disease control while maintaining adequate quality of life (QoL) during the remaining life span. Treatment for BMs consists of different (palliative) options, including surgery, chemotherapy, immunotherapy and radiotherapy.5 One of the concerns with radiotherapy treatment is how to achieve the optimal balance between maximizing anti-tumor effects and minimizing possible adverse side-effects. The two prominent strategies for radiotherapy in BMs are whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). WBRT is typically advised for patients with more than three BMs since treatment covers all brain tissue and has the advantage of sterilizing not-yet visible BMs.6,7 The main disadvantage is that WBRT can lead to radiation-induced tissue damage across the entire brain. SRS has mainly been applied in selected patients with one to three BMs and a favorable prognosis.8 During SRS, high precision localized irradiation is delivered to the BMs in a single fraction to maximize local tumor control and minimize the dose to the surrounding, healthy brain tissue. Patients with BMs compose a vulnerable patient group, since a high percentage of patients already experience cognitive impairment before starting radiotherapy, as a direct result of BMs but also due to previous cancer treatments.9–11 Deteriorated cognitive functions have been related to impaired financial, work and social activities, which are all important in maintaining good QoL and autonomy.12,13 Although literature on the cognitive changes after radiotherapy has been reviewed both for WBRT and SRS separately14,15, to date no publication exists comparing WBRT with SRS in relation to the cognitive outcome after treatment. Since SRS is increasingly being favored over WBRT in current practice16, we performed a systematic review on changes in cognitive functioning provoked by either WBRT or SRS in adult patients 2
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