## 4 Discussion
This is primarily due to the fact that the constraints considered pertain to partial irradiations of lung tissue in EBRT treatments, not suitably matching the simulated irradiation conditions, i.e., uniformly distributed activity distribution. This characteristic also limits the strength and validity of the evaluation of all the volumetric constraints considered. An additional point is brought by evaluating the probability of radiation-induced pneumonitis based on known NTCP curves for partial lung irradiation from EBRT [42], indicating a probability between 10% and 11% for \({}^{90}\)Y and between 35% and 48% for \({}^{166}\)Ho according to the interpolation of the BED concept. However, again, these values should be considered with caution, as they refer to datasets based on partial lung irradiations, where the probability of RP is strongly dependent not only on the absorbed dose but also on the irradiated area. The high dose values recorded in this study should be regarded as entirely case-specific and remarkably influenced by the morphological characteristics of the lung tissue considered, which in this specific case has a significantly low density and a small volume, representing a particular case where dosimetric verification is particularly crucial. To emphasize the importance of the results already discussed, a patient treated with \({}^{166}\)Ho with a LS of approximately 11% was evaluated. This patient was characterized by a lung mass of 908 g and a mean density of 0.28 g/cm\({}^{3}\), compared to the reference phantom lung mass of 727 g and a mean density of 0.22 g/cm\({}^{3}\), and a liver lesion located superficially on the hepatic dome at the liver-lung interface. The SPECT imaging revealed a difference in uptake between the ipsilateral lung and the contralateral one, with the former showing slightly higher activity, primarily attributable to the combined effect of the imaging acquisition protocol and the superficial position of the liver lesion. The prescribed activity for the patient was 4.33 GBq, resulting in an average lung dose of 19.3 Gy from the MC simulation, which can be compared to the analogous value for the phantom with an LS of 10%, which is 26.6 Gy. This significant difference in \(\overline{AD}\) is mainly due to the mass difference with respect to the phantom's lungs. Evaluating the corresponding probability of RP occurrence according to the previously outlined model and within the discussed limits, it is found to be between 10% and 11% for the actual patient and between 18% and 23% for the reference phantom, depending on the considered T\({}_{\mu}\). Lung dosimetry remains a crucial issue in TARE in the presence of LS. The need to pay major attention to the dosimetric analysis of patients with considerable levels of LS, even when below the treatment exclusion levels emphasized by international guidelines, becomes highly significant given the new clinical role that this therapeutic option is assuming, transforming from a simple palliative tool to a curative approach as a bridge to liver transplantation [2] or for downstaging lesions for subsequent surgical intervention [44]. In this context, personalized treatment planning becomes a fundamental tool at the service of clinical practice, shifting the focus from a mere assessment of the amount of activity present in the pulmonary compartment to a specific dosimetric evaluation, both in terms of the mean dose absorbed by lung tissue and in terms of the spatial distribution of the absorbed dose. This evaluation, combined with the use of appropriate constraints on the corresponding DVHs, could help manage the specificities of patients in a targeted manner, potentially expanding the horizon of treatable patients with RE. A useful approach to the decision-making process is certainly the definition of a probability of adverse effects' occurrence at a certain level of exposure of healthy tissue through NTCP curves.