9 General introduction and thesis outline dose to organs at risk, like the hippocampus, and thereby reduce the risk of cognitive decline, hippocampal avoidance (HA-WBRT) is preferred over WBRT when possible. A challenge in radiotherapy treatment, as in any treatment, is achieving the optimal balance between maximizing anti-tumor effects and minimizing adverse sideeffects. This balance is constrained by the underlying physics and limitations of the radiotherapy technique employed. To ensure adequate tumor coverage with appropriate safety margins, two treatment volumes are defined for SRS: 1) gross tumor volume (GTV) and 2) planning treatment volume (PTV). The GTV represents the total volume of the BMS as seen on imaging (Figure 2). The GTV is typically identified based on the hyperintense region in a T1-weighted MRI scans after gadolinium injection. The PTV includes the volume of the GTV plus a 1-3 mm margin, depending on the radiotherapy equipment.18 This so-called error margin is necessary to achieve the desired therapeutic effect while taking into account patient set-up variation and the motion within the radiation positioning mask. Even with high dose fall-off at tumor borders, such as in SRS, some dose gradient will fall outside the tumor, possibly leading to radiation-induced brain injury in the surrounding healthy brain tissue. Figure 1. Biological dose (EQD2) distribution in stereotactic radiosurgery (SRS) and hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shown on a T1-weighted MRI in axial and sagittal view (radiological orientation). Patient A was treated with 1 fraction of 15 Gy and had a single BMs in the left parietal lobe. Patient B was treated with 5 fractions of 4 Gy and had multiple BMs throughout the brain. 1
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