55 Appendices CHAPTER 6 IN – AND EXCLUSION CRITERIA Inclusion criteria: - Age ≥ 18 years; - Either radiographic and/or histologic proof of metastatic brain disease eligible for brain radiation therapy; - Eligible for brain irradiation for prophylaxis or treatment; - Expected survival ≥ 5 months, as determined by Graded Prognostic Assessment (GPA) score; - Sufficient knowledge of the Dutch language to allow reliable use of the standardized tests and understand the study information; - Participation in the COIMBRA cohort, with given consent for filling in quality of life questionnaires. Exclusion criteria: - Standard contraindications for 3T MRI scanning; - Standard contraindications for using the RespirAct RA-MRTM MRI UNIT (see D2 IMDD 2.5 contraindications); - Medical contraindications to limited hypercapnia (known metabolic acidosis or alkalosis); - Unwilling or unable to cooperate with breathing manoeuvres or keeping still; - Noncompliance with prescribed anti-seizure medication; - Severe current neurological or psychiatric diseases not related to the primary malignancy or cerebral metastases; - History of cerebrovascular disease (ischaemic stroke or intracranial haemorrhage); - Non-prophylactic use of > 4 mg dexamethasone on the day of participation; - Cardiovascular disease: congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, and myocardial infarction within past 6 months; - Pulmonary disease: oxygen dependency at rest or with exercise, restrictive lung disease with resting respiratory rate over 15 breaths/min; - Concurrent severe or uncontrolled medical disease (e.g., active systemic infection); - History of bleomycin treatment; - Body weight <30 kg or >100 kg - Pregnancy
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