## 4 Discussion
This translates to the maximum safely administrable activity, based on the variable _LS_ considered, ranging from 2.54 to 0.65 GBq. These results highlight the unreliability of current safety limits for treatment, whether they are based on calculating the lung dose using the single-compartment MIRD model [2; 3], the 20% _LS_ limit [2; 4], or the MLA of approximately 600 MBq [3; 5]. It is also worth noting that in cases of lobar or highly selective treatments, the results presented offer considerable flexibility, potentially making it feasible to treat patients with high levels of _LS_. Nonetheless, we must acknowledge that this study does not tackle the formidable challenge of accurately predicting _LS_ and the biodistribution of microspheres through pre-treatment imaging for \({}^{90}\)Y RE. Lung dosimetry is a major issue in RE and remains a topic of ongoing debate. Increasingly, studies [33] are highlighting the need for more patient-specific approaches, emphasizing how the highly heterogeneous nature of lung can negatively impact approximated dosimetric calculation and thereby underscore the necessity for a personalized calculation approach. For instance, a recent review [34], which provides a general discussion of the state of the art regarding lung dosimetric limits in radioembolization, found that using a standard lung mass of 1 kg leads to a general overestimation of lung mass by an average of 20%. The use of \(MC\) simulations for radiation transport allows to account for the patient-specific tissue description. This was demonstrated by [PERSON] et al. [35] in a detailed dosimetric study on a patient who exhibited a post-treatment unexpected accumulation of microspheres in a specific area of the lungs, analyzing the correlation between the inflammatory state and the absorbed dose in that particular region. Currently, no accurate alternatives to direct \(MC\) simulations exist for lung dosimetry of patients undergoing radioembolization, and no guidelines have been established to assess the role and need for more accurate approaches. The latest European guidelines on radioembolization [3] clearly state that lung absorbed dose assessments must be performed using the mono-compartmental MIRD model. This model relies on available patient information, such as average lung density or the amount of activity in the lungs measured by planar or tomoscintigraphic scans. It is also noteworthy that there are no precise methodologies based on patient imaging in the clinical context to predict microsphere biodistribution in the lungs and \(LS\) for \({}^{90}\)Y RE, due to intrinsic differences between radiotracers (e.g., \({}^{99}\)Tc-MAA vs. \({}^{90}\)Y microspheres). However, new deep-learning-based methodologies are currently under development to predict post-treatment microsphere distribution in the lungs [36]. The role of radioembolization in the clinical landscape is evolving beyond its initial palliative intent to become a potential curative approach [9; 10; 37]. This shift is exemplified by radiation segmentectomy for early-stage HCC, which has proven to be a viable alternative in specific cases where surgery or simple ablation is contraindicated or impossible. For intermediate and advanced HCC, radioembolization has demonstrated effectiveness in downstaging to resection (e.g., for central liver lesions) or transplantation. Various studies have reported better outcomes with radioembolization compared to alternative approaches, such as chemembolization. Even patients with severe conditions such as portal vein thrombosis can undergo radioembolization as a bridge to transplantation, provided careful case selection is performed. This broad application landscape can be further expanded through personalized precision dosimetry, which enables the use of specific activity prescriptions and the delivery of high doses to the lesions. However, this introduces potential risks in managing patients with \(LS\), which must be carefully addressed.