176 Chapter 7 registered to the CT, to plan the radiotherapy and delineate the so-called gross tumor volume (GTV; i.e. brain metastases). The prescribed dose was recalculated into equivalent total doses per 2-Gy fractions (EQD2) to aid comparability between and generalizability to different radiation schemes. The CT, dose maps, planned target volume (PTV) and GTV were extracted for each patient. For the current analysis, the GTV was divided into newly treated brain metastases, resection cavities of brain metastases and previously irradiated brain metastases. Analysis were only performed on newly treated brain metastases. If a patient had multiple brain metastases, averages were calculated from all voxels corresponding to the multiple brain metastasis. Dose maps were subdivided into regions of interests (ROIs) with low (<10 Gy), medium (10-15 Gy) and high (>15 Gy) dose, following previous research on vascular damage described above 10-15 Gy (Figure 1).17 Breathing protocol Hypercapnic stimuli were delivered using a computer-controlled gas blender and sequential delivery system (RespirAct, Thornhill Research Institute, Toronto, Canada). The breathing mask was sealed to the patients’ face using transparent dressings (Tegaderm, 3M, St. Paul, MN, US) to acquire an air tight seal. Before starting the breathing challenges inside the MRI scanner, patients performed a test round with a CO2 challenge which is similar to the CO2 block given during the protocol. Only after successful completion of the test round the breathing challenges inside the scanner were performed (Supplementary Figure 1). The breathing challenges started with a 5-minute baseline period, followed by a block-shaped increase of end-tidal CO2 (PetCO2) 10 mmHg relative to a patient’s baseline for 90 seconds. After this so-called CO2-block, PetCO2 values returned to baseline values for 120 seconds, followed by a PetCO2 ramp increase of 12 mmHg relative to patients’ baseline for 180 seconds after which patients returned to baseline for 90 seconds. Neurocognitive assessment An extensive battery of neuropsychological tests was used to assess cognitive performance both before and three months after SRS. All tests are internationally widely used, standardized psychometric instruments for assessing neurocognitive deficits in the major neurocognitive domains (Supplementary Table 1).22 Each neuropsychological test was scored according to standardized scoring criteria. Individual change in neurocognitive performance post-radiotherapy was assessed and classified using the reliable change index (RCI) as formulated by Jacobson and Truax.23,24 RCI values ≥1.645 present improvement, ≤-1.645 present decline and values not exceeding ±1.645 indicate stable cognitive performance on the task. Change in neurocognitive performance per domain was defined as improved if at
RkJQdWJsaXNoZXIy MTk4NDMw