Impact of coronavirus disease 2019 pandemic on breast cancer surgery using the National Database of Japan.

Various countries have reported a decrease in breast cancer surgeries during the coronavirus disease 2019 (COVID-19) pandemic; however, inconsistent results have been reported in Japan. This study revealed changes in the number of surgeries during the pandemic using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) from January 2015 to January 2021, where insurance claims data from Japan as a whole are comprehensively accumulated. The number of breast-conserving surgeries (BCS) without axillary lymph node dissection (ALND) significantly decreased in July (- 846; 95% confidence interval (CI) - 1190 to - 502) and October 2020 (- 540; 95% CI - 861 to - 218). No decrease was observed for other types of surgery, BCS with ALND, and mastectomy with or without ALND. In the age-specific subgroup analysis, significant and transient reduction in BCS without ALND was observed in all age groups (0-49, 50-69, and ≥ 70 years). The number of BCS without ALND significantly decreased for a relatively short period in the early pandemic stages, suggesting reduced surgery for patients with a relatively low stage of cancer. Some patients with breast cancer might have been left untreated during the pandemic, and an unfavorable prognosis would be a concern.

COVID-19 Vaccine-Associated Lymphadenopathy Mimicking Regrowth of Axillary Lymph Node Metastasis of Lung Adenocarcinoma.

We encountered a woman with re-enlarged axillary lymph nodes during a computed tomography (CT) scan for surveillance of lung adenocarcinoma with axillary lymph node metastasis at the initial diagnosis that had shrunk with standard chemotherapy. We first suspected cancer recurrence and considered a change in the chemotherapeutic regimen. However, after careful history taking regarding the timing of her Coronavirus Disease 2019 (COVID-19) vaccination, and subsequent careful, close follow-up, radiological shrinkage suggested a strictly benign cause. Especially in lung cancer with a medical history of axillary lymph node involvement, cliniciansshould be aware that vaccine-associated lymphadenopathy can mimic cancer recurrence and sometimesprompt serious misjudgment regarding a current treatment course and strategy.

Evaluation of clinically involved lymph nodes with deformable registration in breast cancer radiotherapy.

OBJECTIVES: Modern radiotherapy (RT) techniques require careful delineation of the target. There is no particular RT contouring guideline for patients receiving neoadjuvant chemotherapy (NACT). In this study, we examined the distribution of pre-chemotherapy clinically positive nodal metastases. METHODS: We explored the coverage rate of the RTOG breast contouring guideline by deformable fusion of 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan. We retrospectively evaluated neoadjuvant chemotherapy patients. All PET-CT images were imported into the planning software. We combined the planning CT and the CT images of PET-CT with rigid and then a deformable registration. We manually contoured positive lymph nodes on the CT component of the PET-CT data set and transferred them to planning CT after fusion. We evaluated whether previously contoured lymphatic CTVs, according to the RTOG breast atlas, include GTV-LNs. RESULTS: All breast cancer patients between October 2018 and February 2021 were evaluated from the electronic database. There were 142 radiologically defined positive lymph nodes in 31 patients who were irradiated after NACT. Most LNs (70%) were in the level I axilla. Only 71.1% (n:101) of the whole lymph nodes in 10 patients were totally covered, 22.5% (n:32) partially covered and 6.4% %(n:9) totally undercovered. CONCLUSIONS: The extent of regional nodal areas in the RTOG atlas may be insufficient to cover positive lymph nodes adequately. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions can be helpful to be sure that positive lymph nodes are in the treatment volume. ADVANCES IN KNOWLEDGE: RTOG contouring atlas may be insufficient to cover all involved lymph nodes after NACT. For patients with nodal involvement undergoing neoadjuvant chemotherapy, PET-CT image fusions may help to be sure that positive lymph nodes are in the treatment volume.

Axillary adenopathy detected on breast MRI following COVID-19 vaccination: outcomes and follow-up recommendations.

This retrospective study presents 110 patients with suspected COVID-19 vaccine-related axillary adenopathy on breast MRI. Our study aimed to assess the outcomes of axillary adenopathy detected on breast MRI performed within one year after COVID-19 vaccination. The median time between the COVID-19 vaccine and breast MRI was shorter in patients with detected adenopathy compared to patients without detected adenopathy (6 weeks [2-17] versus 15 [7-24] weeks, p < 0.001). Unilateral axillary adenopathy detected on breast MRI had a low malignancy rate (3.3%), and no cases of malignant axillary adenopathy were diagnosed without a known breast cancer in the ipsilateral breast. Our findings suggest that unilateral axillary adenopathy identified on breast MRI ipsilateral to a recent COVID-19 vaccination can be considered benign in the absence of a suspicious breast finding or known breast cancer. Regardless of vaccine status and timing, unilateral axillary adenopathy detected on MRI evaluation with a known malignancy or suspicious breast finding should be considered suspicious. This will avoid unnecessary scheduling constraints, patient anxiety, and cost, without delaying diagnosis of metastatic breast cancer.

Axillary Lymphadenopathy in the COVID-19 Era: What the Radiologist Needs to Know.

Axillary lymphadenopathy caused by the high immunogenicity of messenger RNA (mRNA) COVID-19 vaccines presents radiologists with new diagnostic dilemmas in differentiating vaccine-related benign reactive lymphadenopathy from that due to malignant causes. Understanding axillary anatomy and lymphatic drainage is key to radiologic evaluation of the axilla. US plays a critical role in evaluation and classification of axillary lymph nodes on the basis of their cortical and hilar morphology, which allows prediction of metastatic disease. Guidelines for evaluation and management of axillary lymphadenopathy continue to evolve as radiologists gain more experience with axillary lymphadenopathy related to COVID-19 vaccines. General guidelines recommend documenting vaccination dates and laterality and administering all vaccine doses contralateral to the site of primary malignancy whenever applicable. Guidelines also recommend against postponing imaging for urgent clinical indications or for treatment planning in patients with newly diagnosed breast cancer. Although conservative management approaches to axillary lymphadenopathy initially recommended universal short-interval imaging follow-up, updates to those approaches as well as risk-stratified approaches recommend interpreting lymphadenopathy in the context of both vaccination timing and the patient's overall risk of metastatic disease. Patients with active breast cancer in the pretreatment or peritreatment phase should be evaluated with standard imaging protocols regardless of vaccination status. Tissue sampling and multidisciplinary discussion remain useful in management of complex cases, including increasing lymphadenopathy at follow-up imaging, MRI evaluation of extent of disease, response to neoadjuvant treatment, and potentially confounding cases. An invited commentary by Weinstein is available online. ©RSNA, 2022.

FDG PET/CT radiomics as a tool to differentiate between reactive axillary lymphadenopathy following COVID-19 vaccination and metastatic breast cancer axillary lymphadenopathy: a pilot study.

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.

Quantitative ultrasound image analysis of axillary lymph nodes to differentiate malignancy from reactive benign changes due to COVID-19 vaccination.

PURPOSE: The aim of this study is to assess the potential of quantitative image analysis and machine learning techniques to differentiate between malignant lymph nodes and benign lymph nodes affected by reactive changes due to COVID-19 vaccination. METHOD: In this institutional review board-approved retrospective study, we improved our previously published artificial intelligence model, by retraining it with newly collected images and testing its performance on images containing benign lymph nodes affected by COVID-19 vaccination. All the images were acquired and selected by specialized breast-imaging radiologists and the nature of each node (benign or malignant) was assessed through a strict clinical protocol using ultrasound-guided biopsies. RESULTS: A total of 180 new images from 154 different patients were recruited: 71 images (10 cases and 61 controls) were used to retrain the old model and 109 images (36 cases and 73 controls) were used to evaluate its performance. The achieved accuracy of the proposed method was 92.7% with 77.8% sensitivity and 100% specificity at the optimal cut-off point. In comparison, the visual node inspection made by radiologists from ultrasound images reached 69.7% accuracy with 41.7% sensitivity and 83.6% specificity. CONCLUSIONS: The results obtained in this study show the potential of the proposed techniques to differentiate between malignant lymph nodes and benign nodes affected by reactive changes due to COVID-19 vaccination. These techniques could be useful to non-invasively diagnose lymph node status in patients with suspicious reactive nodes, although larger multicenter studies are needed to confirm and validate the results.

Axillary Lymph Node Swelling After COVID-19 Booster Vaccination: Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 has been a global pandemic for more than 2 years, and vaccination against COVID-19 using an mRNA vaccine is widespread. The COVID-19 vaccination can cause specific side-effects, such as axillary lymph node swelling; therefore, breast oncologists should pay attention to such occurrences. Initially, only two COVID-19 vaccinations were planned; however, in some countries third or fourth vaccines have been administered. Here, we present a female case who developed axillary lymph node swelling after her third vaccination. We have also reviewed the literature regarding this side-effect after a third or fourth COVID-19 vaccination. CASE REPORT: A 64-year-old woman who came to our clinic regarding a mammography abnormality in her left breast. She had no palpable mass, but a left breast mass was shown by mammography, and ultrasonography and magnetic resonance imaging indicated a hamartoma. At 2 months after her second COVID-19 vaccination when she underwent these tests, she had no axillary lymph node swelling. We planned a follow-up after 6 months. At her next visit, by chance, she underwent ultrasonography 14 days after she received a third COVID-19 vaccination, and a swollen axillary lymph node was observed. CONCLUSION: Axillary lymph node swelling can occur after a third COVID-19 vaccination. Therefore, breast oncologists will have to consider this side-effect of COVID-19 vaccination when diagnosing breast tumors.

Timing and Duration of Axillary Lymph Node Swelling After COVID-19 Vaccination: Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 vaccination is now performed in most of the world to limit the spread of the disease. The first mRNA vaccine was approved in clinical settings and has specific side effects including axillary lymph node swelling, which can be misdiagnosed as breast cancer metastasis. The timing of axillary lymph node swelling and its duration are unclear. Here, we present a Japanese case and review of the existing literature. CASE REPORT: We report the case of a 67-year-old woman with breast calcification. She had regular follow ups in our hospital for this calcification and received ultrasonography of the breast and axilla at every visit. She visited 6 months before having her COVID-19 vaccination, and 7 days and 6 months after the first COVID-19 vaccination. She had a swollen axillary lymph node 7 days after the first vaccination, which although it was improved, remained for 6 months. CONCLUSION: Axillary lymph node swelling occurred 7 days after vaccination and remained up to 6 months after it.

DENEB: Development of new criteria for curability after local excision of pathological T1 colorectal cancer using liquid biopsy.

According to the current international guidelines, high-risk patients diagnosed with pathological T1 (pT1) colorectal cancer (CRC) who underwent complete local resection but may have risk of developing lymph node metastasis (LNM) are recommended additional intestinal resection with lymph node dissection. However, around 90% of the patients without LNM are exposed to the risk of being overtreated due to the insufficient pathological criteria for risk stratification of LNM. Circulating tumor DNA (ctDNA) is a noninvasive biomarker for molecular residual disease and relapse detection after treatments including surgical and endoscopic resection of solid tumors. The CIRCULATE-Japan project includes a large-scale patient-screening registry of the GALAXY study to track ctDNA status of patients with stage II to IV or recurrent CRC that can be completely resected. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective study, within the GALAXY study for patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk stratification criteria for LNM. The aim of this study is to explore the ability of predicting LNM using ctDNA analysis compared with the standard pathological criteria. The ctDNA assay will build new evidence to establish a noninvasive personalized diagnosis in patients, which will facilitate tailored/optimal treatment strategies for CRC patients.

Frequency of Ipsilateral Axillary Lymphadenopathy After the Inactivated COVID-19 Vaccine.

OBJECTIVE: During COVID-19 vaccine development studies, vaccines' efficacy and safety profiles should be carefully investigated. Only a few studies have shown that the COVID-19 vaccine can cause axillary lymphadenopathy on the injection arm. This study aimed to investigate the incidence of axillary lymphadenopathy and imaging findings using B-mode and Doppler ultrasonography (US) examinations in volunteers who had recently been vaccinated against COVID-19. METHODS: The ipsilateral and contralateral axillae of 101 volunteers who received the COVID-19 vaccine were evaluated using B-mode and Doppler US examinations. The volunteers were asked when and to which arm the vaccine had been applied, and the type and dose of the vaccine were recorded. It was also questioned whether the individual experienced any side effects after vaccination, such as pain, tenderness, fever, and redness at the injection site. In addition, the demographic data of the participants, such as age and gender, were recorded. RESULTS: The B-mode US examinations revealed that the long- and short-axis diameters, size, cortical thickness, and asymmetric cortical thickening of the left axillary lymph nodes were significantly higher compared to the right side in individuals having received the CoronaVac vaccine (p<0.05). When the individuals were evaluated separately according to gender, the frequency of cortical thickness and asymmetric cortical thickening in the left axillary lymph nodes was higher than on the right side in both males and females (p=0.011). CONCLUSION: It should be kept in mind that ipsilateral reactive lymphadenopathy may develop after the COVID-19 vaccine. This knowledge can prevent unnecessary axillary lymph node biopsies.

Axillary Lymph Node Swelling Mimicking Breast Cancer Metastasis After COVID-19 Vaccination: A Japanese Case Report and Literature Review.

BACKGROUND/AIM: COVID-19 started to spread as a pandemic in December 2019 and COVID-19 vaccination has been initiated worldwide. The efficacy of vaccination has been scientifically proven, but it might cause axillary lymph node swelling. To diagnose patients with axillary lymph node swelling caused by COVID-19 vaccination, we herein reviewed existing literature on this symptom. CASE REPORT: We report the case of a 70-year-old woman with a breast tumour. She had undergone cecum cancer surgery and regular computed tomography (CT). During breast tumour follow-up, she received scheduled CT that indicated severe axillary lymph node swelling mimicking breast cancer metastasis. We performed aspiration biopsy cytology of that lymph node, and determined this was not cancer metastasis but an effect of the COVID-19 vaccine. We confirmed this diagnosis at one month after computed tomography showed that the lymph node swelling had improved. CONCLUSION: Axillary lymph node swelling can occur after COVID-19 vaccination. Therefore, it is important to consider the effect of the COVID-19 vaccination on axillary lymph node swelling when diagnosing breast tumours.

SARS-CoV-2 mRNA Vaccination Causes Prolonged Increased Cortical Thickening and Vascularity in Ipsilateral Axillary Lymph Nodes.

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks. METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. A total of 11 lateral lymph nodes were identified. Cortical thickness was measured and absence or presence of color Doppler flow in the hilum and lymph node cortex was graded (scale: 0-2). RESULTS: Eleven lateral axillary lymph nodes were biopsied over 24 to 28 weeks. Mean thickness varied through time (P < .001) and was greater weeks 2 to 7 compared to weeks 24 to 28 (mean differences of 2.6 to 1.3; P < .006), but weeks 14 to 17 mean thickness was not different from weeks 24 to 28 (0.57; P = .15). Cortical vascularity was increased in all 11 lymph nodes by week 5. Mean vascularity varied through time (P < .001) and was greater weeks 2 to 14 compared to weeks 24 to 28; mean differences ranged from 1.7 to 0.83 (P < .001). CONCLUSIONS: Serial grey-scale and color Doppler appearance of ipsilateral axillary lymph nodes after mRNA vaccination manifest as increased and prolonged cortical thickening and vascularity that diminishes and approaches normal by 24 to 28 weeks.

Metastatic melanoma in the breast and axilla: A case report.

Metastatic melanoma of the breast is rare, and demonstrates nonspecific imaging findings which may overlap with both benign and malignant pathology.1-3 Immunohistochemical stains are important to confirm the diagnosis, particularly combining S100, a sensitive marker for melanoma, with more specific tumor markers such as Melan-A and HMB-45, and lack of cytokeratin staining.4-7 We present a case of a 64-year-old female who presented for diagnostic imaging of a palpable abnormality in her right breast, with medical history notable for previously excised cutaneous melanoma, recent COVID-19 vaccination, and significant family history of breast cancer. Diagnostic mammogram of the right breast demonstrated a circumscribed mass in the lower inner quadrant corresponding to the area of palpable concern, as well as an additional non-palpable circumscribed mass in the lower inner quadrant. Targeted right breast ultrasound demonstrated corresponding circumscribed cystic versus solid masses as well as a morphologically abnormal right axillary lymph node. Pathologic results after tissue sampling of the two right breast masses and right axillary lymph node all yielded metastatic melanoma.