## 4 Discussion
### Investigation Findings  
Our study indicates agreement between the measurement of both CAC scores and muscle mass area obtained using the freeware Horos and LIFEx software. However, for high values of CAC score, we found some disagreement in Bland-Altman analysis. This finding can be explained by the fact that the two software programs may work with different methods with a slight overestimation of the CAC score by Horos in comparison to LIFEx when the number and the volume of calcified zones increase and the differences between the two software programs are magnified. Yet, it should be taken into account that the observed slight discrepancies might be relevant under other experimental conditions, such as poor image quality. However, discrepancies between software at the algorithm level could not be further investigated because the freeware software source codes are not freely available. However, the observed difference in CAC score seems clinically negligible considering that, categorizing patients according to CAC score categories, the two software programs perfectly agreed in categorizing patients at high risk of CAD.  
Regarding the muscle area, Horos and LIFEx software showed very good agreement. The distributions of the measured values by the two software programs were superimposable, highlighting only a slight increase of the Horos median with respect to LIFEx. [PERSON]'s  
Figure 7: Comparison between muscle areas of two patients (**A,B**), achieved through Horos (green) and LIFEx (red) software. Patient A is a 70-year-old woman with pulmonary carcinoma. Muscle area was 99 cm\({}^{2}\) with Horos and 98 cm\({}^{2}\) with LIFEx. Patient B is a 56-year-old man with prostatic tumor. Muscle area was 206 cm\({}^{2}\) with Horos and 206 cm\({}^{2}\) with LIFEx.  
correlation was high, and the Bland-Altman analysis showed a mean difference between measurements less than a half centimeter squared. In particular, the major discrepancies were noted for small values of muscle areas. This effect is explainable by the variation of the relative error, which increases when the value to be measured decreases and the absolute error remains approximately equal. For the same reason, we observed a slight increase in the Bland-Altman limits of agreement for women as compared to men. Nowadays, oncological patients can have a relatively long life expectancy, but their condition can lead to multiple instrumental examinations that can include iodizing radiation exposure. It is very important to optimize radiation exposure and at the same time to obtain as much information as possible from instrumental examinations. Muscle mass loss and sarcopenia onset during chemotherapy or cancer progression has been reported to have a negative effect on prognosis and on complication onset [8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21]. Some drugs used in chemotherapy are related to cardiotoxicity as well [48; 49; 50; 51; 52]. Patients treated with these drugs usually undergo echocardiography or magnetic resonance for strain and ejection fraction measurement during follow up for cardiac functionality modification [53; 54; 55; 56; 57], but CAC scoring can be feasible as well for cardiac injury monitoring during chemotherapy [58; 34; 59].  
Further, in the era of artificial intelligence, a truly automated method may implement the relevance of the present finding. On the other hand, the two software packages used in this study require a semi-automatic procedure, consisting in the DICOM visualization, then the selection of ROI, and lastly the application of the algorithm of interest. These algorithms are based on grey tone thresholds, and complex algorithms, such as machine learning, are not needed.