Discussion
MM
DISEASE, INFILTRATION, CREST
The interpretation of [There are three major findings after the initial application of our deep learning-based tool in MM: firstly, the automated, volumetric, whole-body assessment of the intensity of BM metabolic activity in PET/CT images is feasible. Secondly, the AI-derived PET/CT biomarkers MTV and TLG are significantly correlated with the visual (subjective) analysis of the extent of BM involvement in [The herein applied deep learning, whole body, volumetric quantification method of [Another distinguishing point between this work and previous ones in the field is that in our study, we went one step further and managed to show a significant moderate correlation between the AI-derived MTV and TLG and two clinically relevant biomarkers in MM. In specific, the demonstration of the correlation between the automated, volumetric PET parameters—derived by four of the evaluated approaches (Approaches 1, 2, 4, and 5)—and the percentage of BM plasma cells derived from biopsies, a main histopathological biomarker in the disease, and the levels of β2-microglobulin, a powerful predictor of survival and a key variable of ISS [The interest in volumetric PET measurements in MM is not new. Fonti et al. were the first to explore the predictive role of MTV and TLG in a mixed group of 47 MM patients who received various therapies. Their analysis was based on the identification of focal lesions and the calculation of SUVRecently, in a retrospective analysis of 185 patients with newly diagnosed MM, Terao et al. investigated the predictive value of pre-treatment MTV and TLG, as assessed by a semi-automated, computer-aided analysis of the PET/CT images, and compared it with conventional PET/CT variables. The authors could show that the high-burden MTV and TLG findings were superior to the conventional high-risk PET/CT variables for outcome prediction, as assessed by PFS and OS [We note some limitations in our study. Foremost, the number of patients enrolled and PET/CT scans analyzed was relatively small. However, the studied cohort is homogeneous, consisting of treatment-naive, symptomatic MM patients examined in terms of an ongoing prospective study. Therefore, the presented findings can only be considered the preliminary results of an ongoing study. Secondly, the vast majority of PET/CT findings were not histopathologically confirmed, which is, obviously, not possible in the clinical setting. However, the demonstration of a significant correlation with two commonly accepted reference standards, namely, the percentage of BM infiltration by malignant plasma cells as derived from biopsies of the iliac crest and the plasma levels of β2-microglobulin, essentially contributed to the validation of the results. Moreover, especially with regard to the diffuse BM uptake pattern, in an effort to reduce the incidence of false positive findings, it was ensured that no included patient had previously received agents or medications, which could lead to a diffusely increased tracer accumulation in the BM, at least one month before the PET/CT study [