## 4 Discussion  
According to cardio-oncology recommendations, strategies for the early detection of cardiotoxicity include the use of biomarkers and cardiac imaging techniques [2; 3; 4] with a multidisciplinary approach [2; 3; 5], with protocols for the prevention and diagnosis of cardiotoxicity in patients with chemotherapy treatment recently defined [2; 4; 8; 34; 41; 42]. The early diagnosis of myocardial damage derived from anthracycline treatment is a crucial factor for reducing the risk or consequences of cardiotoxicity. The quantification of routinely acquired oncological [18]FDG PET imaging studies may provide further insight into the early diagnosis of myocardial impurities, as stated in the literature [13; 14; 15; 16; 19; 20; 21; 22; 23; 24]. The study of the intrinsic characteristics of the images through radiomics has also shown promising potential in the diagnosis of various cardiac diseases [26; 27; 28; 29; 30; 31; 43]. Our results show that of the patients with documented moderate to severe CTRCD\(+\), most of them treated with anthracyclines have a significative decreased metabolic uptake in the intermediate [18]FDG PET study compared with the CTRCD\(-\) group. Moreover, to the best of our knowledge, this is the first study that analyzes the utility of radiomic [18]FDG\(/\)PET features in the follow-up of patients treated with potential cardiotoxic chemotherapy, showing significant differences in the intermediate PET study results between the groups with and without CTRCD. The evidence regarding the use of [18]FDG PET imaging to detect cardiotoxicity at an early stage is still scarce, partly due to the variability in metabolic uptake [13; 14; 15; 16; 19; 20; 21; 22; 23; 24]. Moreover, most studies defined exclusion criteria based on the presence of previous risk factors [13; 14; 15; 16; 22; 23] and therefore do not study the potential predictive value of clinical variables in favor of more homogeneous cohorts. On the contrary, we considered cardiovascular risk factors in this study, findings a higher prevalence of HTN (\(p\) = 0.013) and older age (\(p\) = 0.005) in the CTRCD\(+\) group. The cohort included five patients who received radiotherapy as part of their treatment. Among them, two patients (from the CRTCD\(-\) group) underwent radiotherapy involving the left hemithorax, while the remaining three patients (from the CRTCD\(+\) group) received radiotherapy in areas distant from the left hemithorax, such as the pelvis. While radiotherapy is recognized as an integral component of the treatment strategy for these patients and may influence cardiac functionality, only three patients in the cohort received radiotherapy specifically targeting the left hemithorax. This limits the statistical evaluation of its correlation with altered metabolic uptake patterns. Figure 2: \(H_{Rad}\) index distribution and trends in median values for the CTRCD\(+\) and CTRCD\(-\) groups in the baseline, intermediate, and EOT image studies. The vertical axis is expressed in log scale to evidence the differences between groups. Statistically significant differences between CTRCD groups after multiple-testing correction are indicated with their respective \(p\)-values. CTRCD: cancer therapy-related cardiac dysfunction; EOT: end-of-treatment. Given the routine use of [18]FFDG PET during many oncology treatments, the potential changes in myocardial [18]FFDG uptake became an attractive biomarker in the early detection of cardiotoxicity. This has been evaluated using different approaches, including dose-dependent uptake increase for Adriamycin [13; 21] or doxorubicin-induced [14] cardiotoxicity, focal uptake increase in the right [23] or left ventricle [19; 20; 22] in PET studies performed while on treatment, and myocardial uptake patterns in follow-up PET studies revealing reduced uptake at baseline [14] and increased uptake in intermediate [19; 33] or post-treatment studies [16; 23] in the patients with a higher incidence of cardiac abnormalities.