Purpose: To study the association between ultrasound cortical thickness in reactive post-vaccination lymph nodes and the elicited humoral response and to evaluate the performance of cortical thickness as a predictor of vaccine effectiveness in patients with and without a previous history of COVID-19 infection. Methods: A total of 156 healthy volunteers were recruited and followed prospectively after receiving two COVID-19 vaccination doses using different protocols. Within a week after receiving the second dose, an axillary ultrasound of the ipsilateral vaccinated arm was performed, and serial post-vaccination serologic tests (PVST) were collected. Maximum cortical thickness was chosen as a nodal feature to analyze association with humoral immunity. Total antibodies quantified during consecutive PVST in previously-infected patients and in coronavirus-naïve volunteers were compared (Mann-Whitney U test). The association between hyperplastic-reactive lymph nodes and effective humoral response was studied (odds ratio). The performance of cortical thickness in detecting vaccination effectiveness was evaluated (area under the ROC curve). Results: Significantly higher values for total antibodies were observed in volunteers with a previous history of COVID-19 infection (p < 0.001). The odds ratio associating immunized coronavirus-naïve volunteers after 90 and 180 days of the second dose with a cortical thickness ¿ 3 mm was statistically significant (95% CI 1.52-6.97 and 95% CI 1.47-7.29, respectively). The best AUC result was obtained comparing antibody secretion of coronavirus-naïve volunteers at 180 days (0.738). Conclusions: Ultrasound cortical thickness of reactive lymph nodes in coronavirus-naïve patients may reflect antibody production and a long-term effective humoral response elicited by vaccination. Clinical relevance statement: In coronavirus-naïve patients, ultrasound cortical thickness of post-vaccination reactive lymphadenopathy shows a positive association with protective antibody titers against SARS-CoV-2, especially in the long term, providing new insights into previous publications. Key points: ¿ Hyperplastic lymphadenopathy was frequently observed after COVID-19 vaccination. ¿ Ultrasound cortical thickness of reactive post-vaccine lymph nodes may reflect a long-term effective humoral response in coronavirus-naïve patients.

Objectives To assess ultrasound characteristics of ipsilateral axillary lymph nodes after two doses of four different COVID-19 vaccination protocols, to determine whether these parameters differed with age, and to describe how they changed on follow-up imaging. Methods A total of 247 volunteer employees from our center who had received two doses of COVID-19 vaccination were recruited and followed prospectively. Axillary ultrasound of the ipsilateral vaccinated arm was performed the week after receiving the second dose to analyze lymph node features (number, long-axis, cortical thickness, morphology, and vascular imaging). Axillary lymphadenopathy resulting from four vaccination protocols-mRNA (BNT162b2, mRNA-1273), ChAdOx1-S, and mix-and-match-was compared. Analysis was conducted using the Kruskal-Wallis test and post hoc analysis with Bonferroni corrections. Nodal reactogenicity was evaluated for two age groups: young (< 45 years old) and middle-aged ( >= 45 years old). All parameters were compared between both groups using an unpaired-sample Student t test. A p value < 0.05 was considered statistically significant. Results Significantly higher values for total number of visible nodes, cortical thickness, Bedi's classification (p < 0.001), and vascularity (p < 0.05) were observed in mRNA vaccine recipients compared to full ChAdOx1-S protocol recipients. Moreover, mix-and-match protocol recipients showed greater nodal cortical thickness and higher Bedi's classification than full ChAdOx1-S recipients (p < 0.001). Analyses between age groups revealed greater cortical thickness, Bedi's classification, and color Doppler signal in younger patients (p < 0.05). Conclusions Nodal parameters of Bedi's classification and cortical thickness were more often increased in mRNA and mix-and-match vaccine recipients when compared to ChAdOx1-S vaccine alone, especially in younger patients.

Purpose: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). Methods and materials: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ¿3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. Results: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. Conclusions: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Objectives This study was conducted in order to investigate COVID-19 vaccine influence on unilateral axillary lymph nodes, comparing nodal basal features with their characteristics after the first and second vaccination dose. Methods Ninety-one volunteer employees from our center who participated in the BNT162b2 (Pfizer-BioNTech) vaccination campaign were prospectively recruited. A total of three axillary ultrasound evaluations of the ipsilateral vaccinated arm were performed: before vaccination, the week after the first dose and the week after the second dose. The following findings were recorded: the total number of visible nodes, the maximum measurements of the diameter and cortex, Bedi's classification, and color Doppler evaluation. The collected data were compared using paired-sample Student's t-test for quantitative continuous variables and Wilcoxon rank-sum test for ordinal variables. Additional analyses were performed after classifying patients according to the previous history of COVID-19 disease. Differences among both groups were evaluated with the Mann-Whitney U test. Variables with a p value < 0.05 were considered statistically significant. Results Comparative analyses between the three US examinations showed a statistically significant augmentation of total visible nodes, maximum diameter, cortical thickness, grade of Bedi's classification, and Doppler signal (p < 0.001). Analyses between patients with and without previous COVID-19 infection showed a higher lymph node response in naive patients compared to those who were previously infected. Conclusions According to our results, both doses of COVID-19 vaccine induced an increase of all axillary lymph node parameters with statistically significant differences, especially in coronavirus-naive patients.

Simple Summary New blood vessel formation (angiogenesis) has a crucial role in tumour growth and spread. Bevacizumab is an anticancer therapy that targets angiogenesis by inhibiting the vascular endothelial growth factor (VEGF) and is approved for the treatment of metastatic breast cancer. However, there are no validated methods for predicting which patients will respond to bevacizumab, although some have investigated whether a response can be predicted by using scanning (imaging) techniques that study tumour blood vessels or by using the levels of VEGF markers before treatment. In this study, we used a combination of imaging techniques and VEGF marker levels to show that bevacizumab caused structural and functional changes in the blood vessels of breast tumours and substantially slowed tumour growth. The increasing availability and refinement of imaging technology can help to identify biomarkers that will be able to predict which patients with breast cancer are most likely to respond to bevacizumab. This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2-C5). Tumour proliferation and hypoxic status were evaluated using F-18-fluoro-3 '-deoxy-3 '-L-fluorothymidine (FLT)- and F-18-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p <= 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.

Purpose: To evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost). Material and methods: Patients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT). Results: Forty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034). Conclusions: The MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Background Recently, a new mammography system to perform contrast-enhanced mammography has become available in the market. For the high-energy acquisition, it uses a titanium filter instead of a copper one, reducing the tube load while maintaining image quality. Purpose To retrospectively evaluate the accuracy of contrast-enhanced mammography with a titanium filter (TiCEM) in three readers with different grades of experience. Material and Methods IRB-approved retrospective multicentric lesion by lesion study with 200 lesions, all of them initially classified as BI-RADS categories 0/3/4/5 on mammography and/or ultrasound and with pathological confirmation, in 135 patients. Three readers with different levels of experience (expert, resident, intermediate) blinded to the final diagnosis, retrospectively evaluated the low-energy (LE) images and the combination of LE and recombined (subtracted) images and classified the lesions according to the BI-RADS categories. Reader 1 also categorized the breast density. ROC curves were performed for each reader. Results Out of the 200 lesions, 82 were benign and 118 malignant (20 DCIS, 10 ILC, 88 IDC). The AUCs of LE versus TiCEM for were: Reader 1: 0.7 vs. 0.88, P < 0.001; Reader 2: 0.63 vs. 0.83, P < 0.001; and Reader 3: 0.63 vs. 0.84, P < 0.001. For the three readers, the AUCs of LE versus TiCEM were significantly superior in both dense and non-dense breasts (P < 0.001). Comparing the AUC of LE for Reader 1 (expert) versus the AUC of TiCEM for Reader 2 (resident) there were significant differences (0.7 vs. 0.83, P < 0.001). Conclusion The accuracy of TiCEM was significantly better for all the readers, in both dense and non-dense breasts. The accuracy of a resident reading a TiCEM study was better than the accuracy of an expert radiologist reading LE images.

AimsImmunotherapy is a rising alternative to traditional treatment in breast cancer (BC) patients in order to transform cold into hot immune enriched tumours and improve responses and outcome. A computational modelling approach was applied to quantify modulation effects of immunotherapy and chemotherapy response on tumour shrinkage and progression-free survival (PFS) in naive BC patients. MethodsEighty-three Her2-negative BC patients were recruited for neoadjuvant chemotherapy with or without immunotherapy based on dendritic cell vaccination. Sequential tumour size measurements were modelled using nonlinear mixed effects modelling and linked to PFS. Data from another set of patients (n=111) were used to validate the model. ResultsTumour size profiles over time were linked to biomarker dynamics and PFS. The immunotherapy effect was related to tumour shrinkage (P < .05), with the shrinkage 17% (95% confidence interval: 2-23%) being higher in vaccinated patients, confirmed by the finding that pathological complete response rates in the breast were higher in the vaccinated compared to the control group (25.6% vs 13.6%; P=.04). The whole tumour shrinkage time profile was the major prognostic factor associated to PFS (P < .05), and therefore, immunotherapy influences indirectly on PFS, showing a trend in decreasing the probability of progression with increased vaccine effects. Tumour subtype was also associated with PFS (P < .05), showing that luminal A BC patients have better prognosis. ConclusionsDendritic cell-based immunotherapy is effective in decreasing tumour size. The semi-mechanistic validated model presented allows the quantification of the immunotherapy treatment effects on tumour shrinkage and establishes the relationship between the dynamics of tumour size and PFS.

Background: The use of preoperative breast MRI remains controversial despite being the most sensitive technique for the detection of breast malignancies. Purpose: To evaluate the benefit of preoperative breast MRI after performing the three conventional techniques (DM, US, DBT). To analyze the influence of breast density in the sensitivity of the different imaging techniques. Material and methods: Retrospective review of 280 histologically confirmed breast cancers in 192 women. We reviewed the medical records and evaluated the change of treatment induced by MRI. Also, we assessed the reports of DM and the combination of the different imaging techniques, and categorized them according to ACR density (a-d) and as negative (BI-RADS 1-3) or positive (BIRADS 4 or 5). The gold standard was the pathologic assessment of the surgical specimen. The sensitivity of the different techniques was compared using McNemar test. Results: Among these 192 women the use of MRI did not significantly increase the mastectomy rate (from 16.6% to 17.6%; p = 0.5). The addition of any technique demonstrated a higher sensitivity than DM alone. The sensitivity of DM alone was 52.5% while using all the techniques, including MRI, was 94.3% (p < 0.001). Regardless of breast density pattern, the addition of any technique significantly increased the sensitivity of DM (p < 0.001). Conclusions: The addition of MRI to the three conventional techniques increased the sensitivity but did not significantly modify the rate of mastectomies. Additional techniques increased the sensitivity of DM in both dense and non-dense breasts.

CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQFinv) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQFinv values in PRIME mode were lower for all thicknesses except for 40¿mm of PMMA equivalent, in which IQFinv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts