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Objectives: To evaluate if radiomics with machine learning can differentiate between F-18-fluorodeoxyglucose (FDG)-avid breast cancer metastatic lymphadenopathy and FDG-avid COVID-19 mRNA vaccine–related axillary lymphadenopathy. Materials and methods: We retrospectively analyzed FDG-positive, pathology-proven, metastatic axillary lymph nodes in 53 breast cancer patients who had PET/CT for follow-up or staging, and FDG-positive axillary lymph nodes in 46 patients who were vaccinated with the COVID-19 mRNA vaccine. Radiomics features (110 features classified into 7 groups) were extracted from all segmented lymph nodes. Analysis was performed on PET, CT, and combined PET/CT inputs. Lymph nodes were randomly assigned to a training (n = 132) and validation cohort (n = 33) by 5-fold cross-validation. K-nearest neighbors (KNN) and random forest (RF) machine learning models were used. Performance was evaluated using an area under the receiver-operator characteristic curve (AUC-ROC) score. Results: Axillary lymph nodes from breast cancer patients (n = 85) and COVID-19-vaccinated individuals (n = 80) were analyzed. Analysis of first-order features showed statistically significant differences (p < 0.05) in all combined PET/CT features, most PET features, and half of the CT features. The KNN model showed the best performance score for combined PET/CT and PET input with 0.98 (± 0.03) and 0.88 (± 0.07) validation AUC, and 96% (± 4%) and 85% (± 9%) validation accuracy, respectively. The RF model showed the best result for CT input with 0.96 (± 0.04) validation AUC and 90% (± 6%) validation accuracy. Conclusion: Radiomics features can differentiate between FDG-avid breast cancer metastatic and FDG-avid COVID-19 vaccine–related axillary lymphadenopathy. Such a model may have a role in differentiating benign nodes from malignant ones. Key Points: • Patients who were vaccinated with the COVID-19 mRNA vaccine have shown FDG-avid reactive axillary lymph nodes in PET-CT scans. • We evaluated if radiomics and machine learning can distinguish between FDG-avid metastatic axillary lymphadenopathy in breast cancer patients and FDG-avid reactive axillary lymph nodes. • Combined PET and CT radiomics data showed good test AUC (0.98) for distinguishing between metastatic axillary lymphadenopathy and post-COVID-19 vaccine–associated axillary lymphadenopathy. Therefore, the use of radiomics may have a role in differentiating between benign from malignant FDG-avid nodes. [ABSTRACT FROM AUTHOR]

Simple Summary: In breast cancer, the leading cancer type and the main cause of cancer death in women, achieving pathological complete response after neoadjuvant chemotherapy has been shown to be associated with prolonged overall survival. Hence, the correct assessment and the potential prediction of therapy response have recently become the focus of research. In this study, we predicted pathological complete response prior to neoadjuvant system therapy using 18F-FDG PET/MRI radiomics analysis of the breast. Hence, simultaneous 18F-FDG PET/MRI may enable a more individualized and targeted approach to treatment as well as pretherapeutic patient stratification. Background: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. Methods: A total of 73 female patients (mean age 49 years; range 27–77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2− group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2− receptor status. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to evaluate the value of CA15-3 for the diagnostic integration of molecular imaging findings performed with hybrid positron emission tomography and computed tomography (PETCT) technology. Methods We retrospectively selected 45 patients with a median age of 60 years (range 39-85 years) and a previous history of breast cancer (BC) who had already been treated with surgery and other treatments. Three measurements of CA15-3 were collected within 1 year before PETCT examination, at 6-9 months 3-6 months and 0-3 months before PETCT. The prolonged clinical outcome or imaging follow-up was used to define disease relapse. An increase in tumor marker value was compared with PETCT findings and disease relapse. Sensitivity and specificity for both tests were calculated with respect to clinical outcome. Results Disease relapse was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3 expression levels were significantly higher in BC patients with multiple metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels showed an increase in CA15-3 3-6 months before PETCT could identify BC patients at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a median time of 158 days compared to patients who were negative for both tests and who were free from disease for at least 1 year. Conclusions Our results showed that serial increases in CA15-3 can be used to predict positive PETCT results in BC patients during follow-up. Increased levels of CA15-3 may be considered an early warning sign in patients needing accurate molecular imaging investigations, as they are at higher risk of recurrence. In cases of elevated levels, multiple lesions or liver involvement may exist. Also, patients receiving chemotherapeutic or anti-hormonal treatment who have negative PETCT scans and increased CA15-3 serum levels should be considered at risk for relapse, because the CA15-3-linked biochemical signal of the presence of a tumor can predict positive metabolic imaging. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the value of CA15-3 for the diagnostic integration of molecular imaging findings performed with hybrid positron emission tomography and computed tomography (PETCT) technology. Methods: We retrospectively selected 45 patients with a median age of 60 years (range 39-85 years) and a previous history of breast cancer (BC) who had already been treated with surgery and other treatments. Three measurements of CA15-3 were collected within 1 year before PETCT examination, at 6-9 months 3-6 months and 0-3 months before PETCT. The prolonged clinical outcome or imaging follow-up was used to define disease relapse. An increase in tumor marker value was compared with PETCT findings and disease relapse. Sensitivity and specificity for both tests were calculated with respect to clinical outcome. Results: Disease relapse was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3 expression levels were significantly higher in BC patients with multiple metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels showed an increase in CA15-3 3-6 months before PETCT could identify BC patients at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a median time of 158 days compared to patients who were negative for both tests and who were free from disease for at least 1 year. Conclusions: Our results showed that serial increases in CA15-3 can be used to predict positive PETCT results in BC patients during follow-up. Increased levels of CA15-3 may be considered an early warning sign in patients needing accurate molecular imaging investigations, as they are at higher risk of recurrence. In cases of elevated levels, multiple lesions or liver involvement may exist. Also, patients receiving chemotherapeutic or anti-hormonal treatment who have negative PETCT scans and increased CA15-3 serum levels should be considered at risk for relapse, because the CA15-3-linked biochemical signal of the presence of a tumor can predict positive metabolic imaging. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the diagnostic value of a one-step to a two-step staging algorithm utilizing 18F-FDG PET/MRI in breast cancer patients.Methods: A total of 38 patients (37 females and one male, mean age 57 ± 10 years; range 31-78 years) with newly diagnosed, histopathologically proven breast cancer were prospectively enrolled in this trial. All PET/MRI examinations were assessed for local tumor burden and metastatic spread in two separate reading sessions: (1) One-step algorithm comprising supine whole-body 18F-FDG PET/MRI, and (2) Two-step algorithm comprising a dedicated prone 18F-FDG breast PET/MRI and supine whole-body 18F-FDG PET/MRI.Results: On a patient based analysis the two-step algorithm correctly identified 37 out of 38 patients with breast carcinoma (97%), while five patients were missed by the one-step 18F-FDG PET/MRI algorithm (33/38; 87% correct identification). On a lesion-based analysis 56 breast cancer lesions were detected in the two-step algorithm and 44 breast cancer lesions could be correctly identified in the one-step 18F-FDG PET/MRI (79%), resulting in statistically significant differences between the two algorithms (p = 0.0015). For axillary lymph node evaluation sensitivity, specificity and accuracy was 93%, 95 and 94%, respectively. Furthermore, distant metastases could be detected in seven patients in both algorithms.Conclusion: The results demonstrate the necessity and superiority of a two-step 18F-FDG PET/MRI algorithm, comprising dedicated prone breast imaging and supine whole-body imaging, when compared to the one-step algorithm for local and whole-body staging in breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine if functional parameters extracted from the hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) correlate with the immunohistochemical markers of breast cancer (BC) lesions, to assess their ability to predict BC subtype.Methods: This prospective study was approved by the institution’s Ethics Committee, and all patients provided written informed consent. A total of 50 BC patients at diagnosis underwent PET/MRI before pharmacological and surgical treatment. For each primary lesion, the following data were extracted: morphological data including tumour-node-metastasis stage and lesion size; apparent diffusion coefficient (ADC); perfusion data including forward volume transfer constant (Ktrans), reverse efflux volume transfer constant (Kep) and extravascular extracellular space volume (Ve); and metabolic data including standardized uptake value (SUV), lean body mass (SUL), metabolic tumour volume and total lesion glycolysis. Immunohistochemical reports were used to determine receptor status (oestrogen, progesterone, and human epidermal growth factor receptor 2), cellular differentiation status (grade), and proliferation index (Ki67) of the tumour lesions. Correlation studies (Mann-Whitney U test and Spearman’s test), receiver operating characteristic (ROC) curve analysis, and multivariate analysis were performed.Results: Association studies were performed to assess the correlations between imaging and histological prognostic markers of BC. Imaging biomarkers, which significantly correlated with biological markers, were selected to perform ROC curve analysis to determine their ability to discriminate among BC subtypes. SUVmax, SUVmean and SUL were able to discriminate between luminal A and luminal B subtypes (AUCSUVmean = 0.799; AUCSUVmax = 0.833; AUCSUL = 0.813) and between luminal A and nonluminal subtypes (AUCSUVmean = 0.926; AUCSUVmax = 0.917; AUCSUL = 0.945), and the lowest SUV and SUL values were associated with the luminal A subtype. Kepmax was able to discriminate between luminal A and luminal B subtypes (AUC = 0.779), and its highest values were associated with the luminal B subtype. Ktransmax (AUC = 0.881) was able to discriminate between luminal A and nonluminal subtypes, and the highest perfusion values were associated with the nonluminal subtype. In addition, ADC (AUC = 0.877) was able to discriminate between luminal B and nonluminal subtypes, and the lowest ADCmean values were associated with the luminal B subtype. Multivariate analysis was performed to develop a prognostic model, and the best predictive model included Ktransmax and SUVmax parameters.Conclusion: Using multivariate analysis of both PET and MRI parameters, a prognostic model including Ktransmax and SUVmax was able to predict the tumour subtype in 38 of 49 patients (77.6%, p < 0.001), with higher accuracy for the luminal B subtype (86.2%). [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues. Methods: A total of 36 patients underwent a whole-body PET/CT scan 1h after injection and an average of 62min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle. Results: Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ =0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ =0.95–0.97; p <0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ =0.91; p <0.0001), while moderate correlations were found for the other normal organ tissues (ρ =0.36–0.61; p <0.05). Conclusions: PET/MRI showed equivalent performance in terms of qualitative lesion detection to PET/CT. Despite significant differences in tracer uptake quantification, due to either methodological and biological factors, PET/MRI and PET/CT measurements in lesions and normal organ tissues correlated well. This study demonstrates that integrated whole-body PET/MRI is feasible in a clinical setting with high quality and in a short examination time. [Copyright &y& Elsevier]

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies. [ABSTRACT FROM AUTHOR]