Radiomic Applications on Digital Breast Tomosynthesis of BI-RADS Category 4 Calcifications Sent for Vacuum-Assisted Breast Biopsy.

BACKGROUND: A fair amount of microcalcifications sent for biopsy are false positives. The study investigates whether quantitative radiomic features extracted from digital breast tomosynthesis (DBT) can be an additional and useful tool to discriminate between benign and malignant BI-RADS category 4 microcalcification. METHODS: This retrospective study included 252 female patients with BI-RADS category 4 microcalcifications. The patients were divided into two groups according to micro-histopathology: 126 patients with benign lesions and 126 patients with certain or possible malignancies. A total of 91 radiomic features were extracted for each patient, and the 12 most representative features were selected by using the agglomerative hierarchical clustering method. The binary classification task of the two groups was carried out by using four different machine-learning algorithms (i.e., linear support vector machine (SVM), radial basis function (RBF) SVM, logistic regression (LR), and random forest (RF)). Accuracy, sensitivity, sensibility, and the area under the curve (AUC) were calculated for each of them. RESULTS: The best performance was achieved using the RF classifier (AUC = 0.59, 95% confidence interval 0.57-0.60; sensitivity = 0.56, 95% CI 0.54-0.58; specificity = 0.61, 95% CI 0.59-0.63; accuracy = 0.58, 95% CI 0.57-0.59). CONCLUSIONS: DBT-based radiomic analysis seems to have only limited potential in discriminating benign from malignant microcalcifications.

Structured reporting of x-ray mammography in the first diagnosis of breast cancer: a Delphi consensus proposal.

BACKGROUND: Radiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer. METHODS: A working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach's alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation. RESULTS: The final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach's alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach's alpha (Cα) correlation coefficient was 0.90. CONCLUSIONS: Structured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

Technical evaluation of image quality in synthetic mammograms obtained from 15° and 40° digital breast tomosynthesis in a commercial system: a quantitative comparison.

Digital breast tomosynthesis (DBT) has recently gained interest both for breast cancer screening and diagnosis. Its employment has increased also in conjunction with digital mammography (DM), to improve cancer detection and reduce false positive recall rate. Synthetic mammograms (SMs) reconstructed from DBT data have been introduced to replace DM in the DBT + DM approach, for preserving the benefits of the dual-acquisition modality whilst reducing radiation dose and compression time. Therefore, different DBT models have been commercialized and the effective potential of each system has been investigated. In particular, wide-angle DBT was shown to provide better depth resolution than narrow-angle DBT, while narrow-angle DBT allows better identification of microcalcifications compared to wide-angle DBT. Given the increasing employment of SMs as supplement to DBT, a comparison of image quality between SMs obtained in narrow-angle and wide-angle DBT is of practical interest. Therefore, the aim of this phantom study was to evaluate and compare the image quality of SMs reconstructed from 15° (SM15) and 40° (SM40) DBT in a commercial system. Spatial resolution, noise and contrast properties were evaluated through the modulation transfer function (MTF), noise power spectrum, maps of signal-to-noise ratio (SNR), image contrast, contrast-to-noise ratio (CNR) and contrast-detail (CD) thresholds. SM40 expressed higher MTF than SM15, but also lower SNR and CNR levels. SM15 and SM40 were characterized by slight different texture, and a different behavior in terms of contrast was found. SM15 provided better CD performances than SM40. These results suggest that the employment of wide/narrow-angle DBT + SM images should be optimized based on the specific image task.

Average absorbed breast dose (2ABD): an easy radiation dose index for digital breast tomosynthesis.

BACKGROUND: To propose a practical and simple method to individually evaluate the average absorbed dose for digital breast tomosynthesis. METHODS: The method is based on the estimate of incident air kerma (ka,i) on the breast surface. An analytical model was developed to calculate the ka,i from the tube voltage, tube load, breast thickness, x-ray tube yield, and anode-filter combination. A homogeneous phantom was employed to simulate the breast in experimental measurements and to assess the dose-depth relationship. The ka,i values were employed to calculate the "average absorbed breast dose" (2ABD) index. Four mammographic units were used to develop and test our method under many conditions close to clinical settings. The average glandular dose (AGD) calculated following the method described by Dance et al., and the 2ABD computed through our method (i.e., from the exposure parameters) were compared in a number of conditions. RESULTS: A good agreement was obtained between the ka,i computed through our model and that measured under different clinical conditions: discrepancies < 6% were found in all conditions. 2ABD matches with a good accuracy the AGD for a 100% glandular-breast: the minimum, maximum, and mean differences were < 0.1%, 7%, and 2.4%, respectively; the discrepancies increase with decreasing breast glandularity. CONCLUSIONS: The proposed model, based on only few exposure parameters, represents a simple way to individually calculate an index, 2ABD, which can be interpreted as the average absorbed dose in a homogeneous phantom, approximating a 100% glandular breast. The method could be easily implemented in any mammographic device performing DBT.

Tolerability and Efficacy of Treatment With Azacytidine as Prophylactic or Preemptive Therapy for Myeloid Neoplasms After Allogeneic Stem Cell Transplantation.

INTRODUCTION/BACKGROUND: Azacytidine (AZA) has been used as a promising treatment for relapse after allogeneic transplantation. A clear benefit has been demonstrated when treating patients with a reduced disease burden, thus a prophylactic and preemptive approach to these patients has emerged. MATERIALS AND METHODS: We retrospectively analyzed patients with myeloid malignancies treated with azacytidine in the posttransplantation setting between September 2013 and April 2018 in a single tertiary care hospital. Of 32 patients analyzed, 21 were treated for prophylactic use and 11 preemptively, with a median follow-up of 20 months. Prophylactic treatment consisted of AZA at 32 mg/m2 for 5 days every 28 days, and preemptive treatment of AZA 75 mg/m2 for 5 or 7 days per cycle. In addition, 10 patients received one or more donor lymphocyte infusions (DLIs). Two patients presented with infectious complications demanding hospitalization, and 13 patients (10 in the prophylactic group and 3 in the preemptive group) presented graft-versus-host disease (GvHD). Of patients who had GvHD, 3 needed treatment discontinuation. Overall, 12 patients suspended treatment, 8 for disease progression and 1 due to patient request. RESULTS: In the prophylactic group, all patients are alive at 1 year with an event-free survival (EFS) of 95%, as only 1 patient relapsed. In the preemptive group, 1-year EFS was 54% and 1-year overall survival was 82%. CONCLUSION: Low-dose AZA in posttransplantation patients with myeloid neoplasms is a well-tolerated therapy with the potential to prevent relapse and maintain stable remissions. Randomized prospective trials are needed to determine patient selection and dosage, timing, and duration of treatment.

Real-life data on safety and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma.

Autologous stem cell transplantation (ASCT) is still debatable in treatment of patients over 65 years with multiple myeloma (MM). We performed a retrospective analysis of newly diagnosed MM patients who underwent ASCT between January 2010 and July 2016. A non-transplanted group with similar clinical characteristics, aged 65-70 years old, diagnosed and treated in the same timeline was used for comparison. We analyzed a total of 155 patients, 132 of which underwent ASCT (≤ 65 years, n = 103, median 56 years; > 65 years, n = 29, median 67 years) and 23 non-transplanted (median 68 years). Conditioning consisted of melphalan 200 mg/m2 (MEL200) in younger patients and melphalan 140 mg/m2 (MEL140) in half of elderly patients. Stratifying by age, there were no statistically significant differences concerning transplant-related myelotoxicity and non-hematopoietic toxicity; however, elderly patients conditioned with MEL200 had higher needs of transfusional support and more days of intravenous antibiotics. Those patients also had higher needs of transfusional support, higher grade of mucositis (p = 0.028), and more days of intravenous antibiotics (p = 0.019) than the elderly transplanted with MEL140. Global transplant-related mortality was 3.8%. Survival was not influenced by age. Non-transplanted elderly patients had comparable disease features, and induction response was similar in both groups (before ASCT in the transplanted cohort). Survival of transplanted elderly patients was superior to non-transplanted (OS, 59 months vs 30 months, p = 0.037; EFS, 45 months vs 27 months, p = 0.014). Selected elderly patients when transplanted have similar disease response and survival as younger patients. A higher dose of melphalan has more toxicity, but it is globally a well-tolerated procedure.

Doxycycline, an Inhibitor of Mitochondrial Biogenesis, Effectively Reduces Cancer Stem Cells (CSCs) in Early Breast Cancer Patients: A Clinical Pilot Study.

Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of "stemness" (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t-test) and ANOVA. Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p-value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups. Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies.

Magnetic resonance (MR) features in triple negative breast cancer (TNBC) vs receptor positive cancer (nTNBC).

Few reports in literature describe triple negative breast cancer (TNBC) imaging findings. Aim of the study is to determine MR-features of TNBC compared to receptor positive cancer (nTNBC). From May 2014 to May 2015, we retrospectively enrolled 31 consecutive patients with histological diagnosis of TNBC and a control group of 31 consecutive nTNBC observed in the same period, out of 602 cancer, diagnosed in our department in the same year. Histopathological analysis and MR-features of TNBC (31 patients) were compared to nTNBC (31 patients). MR-features included dimension, fibroglandular tissue (FGT), background parenchimal enhancement (BPE), mass shape, margins, presence of rim, intratumoral signal intensity in T2w, uni-multifocality, kinetic curves. All patients were examined with MR 1,5T (Magnetom Simphony Tim, Siemens Healthcare) performing T2w fat-sat and contrast enhanced high temporal and spatial resolution T1w before and after injection of Gadolinium. 62 staging MR were reviewed. Median age was 50 (30-78ys) with a standard deviation of 10,9. TNBC showed 3 MR features in concordance with current literature: rim enhancement, hyperintensity in T2 sequence and unifocality. Rim enhancement was shown in 67.7% of TNBC (21/31) and 29% of nTNBC (9/31). Higher T2w values were shown in 83.9% of TNBC (26/31) and 58.1% of nTNBC (18/31). Cancer was multifocal in 7/31 (22.6%) of TNBC and 19/31 (61.3%) nTNBC. No correlation was found for dimension (p=0.12), FGT (p=0.959), BPE (p=0.596), homogeneity of enhancement (p=0.43), margins (p=0.671) and kinetic (p=0.37). Multivariate analysis demonstrated that rim enhancement and unifocality correlated independently with TNBC group. Area under ROC curve of our model is 0.835. Furthermore, we evaluated the clinical outcome of all 31 TNBC patients in a follow-up time ranging from 24months to 36months separating them in a free-survival group (23 women) and a recurrence group (8 women with local recurrence or distant metastasis): only kinetic curves resulted to be significantly higher in recurrence group (p=0.042).

Average absorbed breast dose in mammography: a new possible dose index matching the requirements of the European Directive 2013/59/EURATOM.

BACKGROUND: The new European Directive 2013/59/EURATOM requires that patients are informed about the risk associated with ionising radiation and that detailed information on patient exposure is included in the radiological report. This implies a revision of the routinely used dose indexes to obtain quantities related to individual exposure evaluable from acquisition parameters. Here we propose a new mammography dose index consistent with the average glandular dose (AGD). METHODS: An equation has been developed for calculating the average absorbed breast dose (2ABD). It depends on incident air kerma ka,i and on energy absorption coefficient µen; ka,i can be calculated for each anode-filter combination, based on kVp, mAs, the yield of the tube used Ytb , and the breast thickness d; µen depends on kVp and has been evaluated for each anode-filter combination. 2ABD has been compared to AGD evaluated by Dance or Wu methods, which represent the reference standards, for 20 patients of our university hospital. RESULTS: The incident air kerma ka,i , calculated as a function of kVp, mAs, Ytb and d, was in good agreement with the same quantity directly measured: the relative uncertainty is < 0.10. The results of the comparison between 2ABD and AGD evaluated by both Dance and Wu methods appear to be consistent within the uncertainties. CONCLUSIONS: 2ABD is easily evaluable for each mammogram from the acquisition parameters. It can be proposed as a new suitable dose index, consistent with AGD, matching the requirements of the 2013 European Directive.

The role of mean diffusivity (MD) as a predictive index of the response to chemotherapy in locally advanced breast cancer: a preliminary study.

OBJECTIVE: To evaluate the role of mean diffusivity (MD) as a predictive index of the response to chemotherapy in locally advanced breast cancer. METHODS: Twenty-one women referred to our institution with a diagnosis of locally advanced breast cancer underwent magnetic resonance imaging (MRI) studies at 1.5 T before beginning and after completing combined neoadjuvant chemotherapy. The examination protocol included an EPI sequence sensitised to diffusion (b-value 1,000 s/mm(2)) and three-dimensional (3D) coronal T1 sequences before and after intravenous contrast medium. Tumours were delineated by using dynamic MR acquisition before and after chemotherapy. The percentage of tumour volume reduction (PVR) and pre-(MD(pre)) and post-therapy (MD(post)) MD values were computed for each lesion. RESULTS: PVR >or= 65% was observed in 17/21 patients (responders). MD(pre) of responders (0.99 +/- 0.27 10(-3) mm(2)/s) was significantly (p = 0.025) lower than MD(pre) of non-responders (1.46 +/- 0.33 10(-3) mm(2)/s). Moreover, in patients as a whole PVR significantly correlated (p = 0.01, r = -0.54) with MD(pre). MD(post) (1.26 +/- 0.39 10(-3) mm(2)/s) of responders was significantly(p = 0.024) higher than MD(pre) (0.99 +/- 0.27 mm(2) 10(-3) mm(2)/s), whereas non-responders MD(post) (1.00 +/- 0.14 10(-3) mm(2)/s)did not increase compared with MD(pre) (1.46 +/- 0.33 10(-3) mm(2)/s). CONCLUSIONS: This preliminary study seems to indicate that low values of pre-chemotherapy MD may identify, before starting treatment, the patients with higher probability of response in terms of percentage of volume reduction of the lesion. MD may represent a complementary parameter useful to correctly select patients for neoadjuvant chemotherapy.

Differentiation of benign and malignant breast microcalcifications: mammography versus mammography-sonography combination.

PURPOSE: The aim of this study was to determine the diagnostic contribution of high-frequency sonography in the diagnosis of isolated clustered microcalcifications detected by mammography. MATERIAL AND METHODS: 238 women (aged 3198) with isolated clustered microcalcifications were examined by mammography and subsequently by high frequency sonography (13 MHz) at the site of microcalcification. 170 underwent surgery. 94 were affected by cancer and 76 by benign pathology. The other 68 were considered to have benign microcalcifications after three years follow-up. The ROC statistical technique was employed to compare the diagnostic role of mammography alone versus the combination of mammography and sonography. The area under the ROC curves was calculated by the Wilcoxon method, without any hypothesis on the distribution of the statistical data. RESULTS: The microcalcifications were neoplastic in 39.5% of cases. The difference between the areas under the mammography ROC curve (area = 0.807, standard error = 0.03) and the mammography-sonography ROC curve (area = 0.819, standard error = 0.028) was not statistically significant (p > 0.05). CONCLUSIONS: The higher sensitivity of mammography-sonography combination demonstrates that it may be useful to perform sonography following mammography when mammography yields a diagnosis of non malignant pathology.