A national survey investigating the impact of the COVID-19 pandemic on core and higher breast radiology training in the UK.

AIM: To investigate the impact of the COVID-19 pandemic on core and higher breast radiology training in the UK from the perspective of trainees and new consultants. MATERIALS AND METHODS: A survey comprising 25 questions was distributed to UK radiology trainees via the regional Junior Radiologists Forum representatives under the auspices of the British Society of Breast Radiology (BSBR). RESULTS: Sixty-nine eligible responses were received representing all UK training regions. Fifty-five per cent of respondents completing either a core or higher breast rotation felt that the pandemic had a negative effect on their breast training. There was an overall reduction in exposure to the key breast imaging methods when rotations took place during the pandemic. Completing a core breast rotation during the pandemic was less likely to attract trainees to higher breast training. Three out of four breast radiology consultants in their first year after receiving their Certificate of Completion of Training (CCT) felt the pandemic reduced their preparedness for becoming consultants. Positive outcomes included the increased use of online educational resources and remote multidisciplinary meetings. CONCLUSIONS: As well as having a negative impact on breast radiology training overall, the pandemic has had a detrimental effect on attracting trainees to breast radiology as a future career. It is of key importance that trainees have a positive core breast rotation as this experience appears central to many trainees' decisions to pursue higher breast training. Increased use of online learning resources has also been positively received and is a valuable approach to learning that can be maintained in the longer term.

Opportunities in cancer imaging: risk-adapted breast imaging in screening.

In the UK, women between 50-70 years are invited for 3-yearly mammography screening irrespective of their likelihood of developing breast cancer. The only risk adaption is for women with >30% lifetime risk who are offered annual magnetic resonance imaging (MRI) and mammography, and annual mammography for some moderate-risk women. Using questionnaires, breast density, and polygenic risk scores, it is possible to stratify the population into the lowest 20% risk, who will develop <4% of cancers and the top 4%, who will develop 18% of cancers. Mammography is a good screening test but has low sensitivity of 60% in the 9% of women with the highest category of breast density (BIRADS D) who have a 2.5- to fourfold breast cancer risk. There is evidence that adding ultrasound to the screening mammogram can increase the cancer detection rate and reduce advanced stage interval and next round cancers. Similarly, alternative tests such as contrast-enhanced mammography (CESM) or abbreviated MRI (ABB-MRI) are much more effective in detecting cancer in women with dense breasts. Scintimammography has been shown to be a viable alternative for dense breasts or for follow-up in those with a personal history of breast cancer and scarring as result of treatment. For supplemental screening to be worthwhile in these women, new technologies need to reduce the number of stage II cancers and be cost effective when tested in large scale trials. This article reviews the evidence for supplemental imaging and examines whether a risk-stratified approach is feasible.

Associations between the ultrasound features of invasive breast cancer and breast cancer specific survival.

AIM: To assess whether ultrasound features of breast cancer are associated with breast cancer specific survival (BCSS). MATERIALS AND METHODS: Within a single breast service, data was collected prospectively (April 2010-April 2012) from 319 consecutive women (mean age 63 years) with 335 ultrasound-visible invasive breast cancers. Ultrasound features were evaluated retrospectively from the recorded images according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon by a radiologist blinded to outcomes. Survival and cause of death were ascertained from local and national sources. Kaplan-Meier survival curves were generated, and statistical significance tested using the log-rank test. RESULTS: Mean follow-up in those alive was 80.9 months. Thirty breast cancer deaths and 45 non-breast cancer deaths occurred. Five-year BCSS in the presence of distal acoustic enhancement was 76% compared to 88%, 96%, and 100% for those with distal shadowing, no distal effect or combined effect respectively (p<0.0002). Patients with sonographic skin involvement had 73% 5-year BCSS compared to 92% for no skin involvement (p<0.0001). Focal oedema was associated with 56% 5-year BCSS compared to 89% for those without (p=0.0002). A significant association was demonstrated between ultrasound tumour size and BCSS (p<0.0001). At multivariate analysis, skin changes, distal enhancement, and focal oedema maintained prognostic significance. CONCLUSION: Distal enhancement, focal oedema, and skin involvement have strong associations with breast cancer death. These factors could be taken into account, along with lesion size and other commonly used preoperative prognostic features, when considering management of women with breast cancer.

Identification of pathological complete response after neoadjuvant chemotherapy for breast cancer: comparison of greyscale ultrasound, shear wave elastography, and MRI.

AIM: To assess the value of post-treatment shear-wave elastography (SWE) parameters (maximum stiffness [Emax], mean stiffness [Emean], and standard deviation [SD]) compared to greyscale ultrasonography (US) and magnetic resonance imaging (MRI) in identifying pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer. MATERIALS AND METHODS: In a prospective cohort study, 80 patients receiving NACT for breast cancer underwent baseline and post-treatment US, SWE, and MRI examinations. Four SWE images in two orthogonal planes were obtained. Maximum greyscale US diameter and maximum diameter of lesion enhancement on MRI were measured. Percentage reductions between baseline and post-treatment scans were calculated for MRI and greyscale US diameter, and Emean, Emax, and SD. The percentage reduction in Emean and US diameter were also analysed as a combination. Analysis was undertaken using receiver operating characteristic (ROC) curves and the chi-squared test. RESULTS: pCR occurred in 21 of 80 (26%) women. The area under the ROC curve (AUC) for pCR of percentage reductions in Emean, Emax, SD, and greyscale US diameter were 0.89, 0.85, 0.75, and 0.86, respectively. The combination of percentage reductions in Emean and greyscale ultrasound diameter yielded an AUC of 0.92, which is similar to the AUC for MRI of 0.96 (p=0.28). CONCLUSIONS: SWE combined with greyscale US shows promise for end-of-treatment identification of response to NACT in women with breast cancer, with accuracies similar to breast MRI. This technique could be used to inform surgical decision-making after NACT.

Breast density: why all the fuss?

The term "breast density" or mammographic density (MD) denotes those components of breast parenchyma visualised at mammography that are denser than adipose tissue. MD is composed of a mixture of epithelial and stromal components, notably collagen, in variable proportions. MD is most commonly assessed in clinical practice with the time-honoured method of visual estimation of area-based percent density (PMD) on a mammogram, with categorisation into quartiles. The computerised semi-automated thresholding method, Cumulus, also yielding area-based percent density, is widely used for research purposes; however, the advent of fully automated volumetric methods developed as a consequence of the widespread use of digital mammography (DM) and yielding both absolute and percent dense volumes, has resulted in an explosion of interest in MD recently. Broadly, the importance of MD is twofold: firstly, the presence of marked MD significantly reduces mammographic sensitivity for breast cancer, even with state-of-the-art DM. Recognition of this led to the formation of a powerful lobby group ('Are You Dense') in the US, as a consequence of which 32 states have legislated for mandatory disclosure of MD to women undergoing mammography. Secondly, it is now widely accepted that MD is in itself a risk factor for breast cancer, with a four-to sixfold increased relative risk in women with PMD in the highest quintile compared to those with PMD in the lowest quintile. Consequently, major research efforts are underway to assess whether use of MD could provide a major step forward towards risk-adapted, personalised breast cancer prevention, imaging, and treatment.

A randomized phase III study of 72 h infusional versus bolus bleomycin in BEP (bleomycin, etoposide and cisplatin) chemotherapy to treat IGCCCG good prognosis metastatic germ cell tumours (TE-3).

BACKGROUND: Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1%-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared with the conventional weekly boluses given as part of standard BEP chemotherapy. PATIENTS AND METHODS: A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1 : 1 randomization. They were stratified for age, smoking history and renal function. Patients received either conventional BEP with weekly bleomycin (30 000 units/week i.v. bolus) or as a 90 000 unit infusion on day 1 over 72 h. The primary endpoint was CT assessed lung toxicity, secondary endpoints included progression-free survival (PFS), changes in lung function testing and quality of life. Repeated measures mixed effects model was used to analyse the data. RESULTS: CT assessed lung toxicity for the infusional and conventional arm patients were respectively 80% versus 62% at the end of treatment and 54% versus 51% at 1-year post-treatment. There was no significant difference between the two arms for CT assessed lung toxicity (estimated regression coefficient = 1.4, 95% CI: -0.36, 3.16). Older patients had higher toxicity (coefficient = 4.81, 95% CI: 3.04, 6.58). Lung toxicity increased after 1 cycle and peaked at end of treatment (P ≤ 0.002) and then declined. Lung function testing did not predict for subsequent lung damage. The median follow-up was 2.5 years. Two-year PFS rate (infusional: 93%, conventional: 94%; hazard ratio =0.91, 95% CI: 0.33, 2.52) was similar. Cough (P = 0.002) but not shortness of breath (P ≥ 0.09) was associated with bleomycin toxicity. CONCLUSIONS: Infusional bleomycin has no advantage over standard administration. It supports abandoning routine pulmonary function testing, instead the presence of cough should be sought and the early use of CT scanning of the chest to evaluate potential lung toxicity is preferred.

Clinical performance of Siemens digital breast tomosynthesis versus standard supplementary mammography for the assessment of screen-detected soft-tissue abnormalities: a multi-reader study.

AIM: To compare the diagnostic accuracy of standard screening images plus single-view digital breast tomosynthesis (DBT), using Siemens DBT equipment, with standard screening images plus supplementary mammographic views in non-calcific, screen-detected mammographic abnormalities. MATERIALS AND METHODS: Participants were unselected women aged 50-69 years recalled within a population-based European breast screening programme for assessment of soft-tissue mammographic abnormalities. Supplementary mammographic views (SMVs) and DBT were performed in all cases. A range of equipment was used for screening and supplementary mammography, but all DBT examinations were performed using the Siemens Mammomat Inspiration. A retrospective multi-reader study including 238 cases for whom either histology or at least 2 years' follow-up was available was performed with eight suitably accredited UK breast screening personnel reading all cases under both conditions, with temporal separation. Readers were blinded to case outcomes and findings from other examinations. Diagnostic accuracy using receiver operating characteristic (ROC) analysis was compared between screening plus SMV images and screening plus DBT images. The study was powered to detect a 3% inferiority margin in diagnostic accuracy between methods. RESULTS: The final sample with complete data available for analysis included 195 benign cases (1,560 reads) and 35 malignant cases (280 reads). The DBT method yielded a slightly higher area under the curve (AUC) value than the SMV method (0.870 versus 0.857), but the difference was not statistically significant (p=0.4890), indicating that the methods have equivalent accuracy. CONCLUSION: Siemens DBT demonstrates equivalent diagnostic accuracy according to ROC curve analysis when used in place of SMVs in screen-detected soft-tissue mammographic abnormalities.

Stiffness at shear-wave elastography and patient presentation predicts upgrade at surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma in situ.

AIM: The aim of this study is to establish predictors of invasion in lesions yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Patients subjected to ultrasound-guided core biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data between invasive and non-invasive masses. Data recorded included the mammographic and ultrasound features, the referral source, and grade of DCIS in the biopsy. The chi-square test was used to detect statistical significance. RESULTS: Of 57 lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients with stiff lesions were more likely to have invasion than patients presenting through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33], p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors showed a relationship with invasion. Combining the two predictors of invasion improved risk stratification with symptomatic and stiff lesions having a risk of invasion of 67% (12 of 18) and soft lesions presenting at screening having only a 17% (2 of 12) risk of invasion (p=0.02). CONCLUSION: Stiffness on SWE and the referral source of the patient are predictors of occult invasion in women with an ultrasound-guided core biopsy diagnosis of DCIS.

Acute pancreatitis: a comparison of intervention rates precipitated by early vs guideline CT scan timing.

AIM: To assess whether computed tomography (CT) examination earlier in acute pancreatitis (AP) precipitates any surgical or radiological intervention. MATERIALS AND METHODS: A single-centre retrospective cohort study comparing intervention rates in AP precipitated by early (<6 day of admission, n=100) and UK guideline (≥6 day of admission, n=103) CT examinations. RESULTS: No intervention was precipitated by performing CT before the sixth day of admission in AP. A statistically significant larger number of interventions were precipitated when CT was performed on the sixth day or later (p<0.05). Of note, this study was conducted using day of admission, rather than day of symptom onset. Six patients underwent repeat CT examination in the same admission after an early CT examination. CONCLUSION: Performing CT before the sixth day of admission does not lead to earlier intervention. Such early examinations waste resources and may offer false reassurance to clinicians.

Factors influencing the stiffness of fibroadenomas at shear wave elastography.

AIM: To identify which features of fibroadenomas are associated with false-positive findings at shear wave elastography (SWE). MATERIALS AND METHODS: A total of 151 patients with histologically confirmed fibroadenomata were identified from a prospective database, from a single breast unit. The following features were assessed by two observers who were unaware of the SWE findings: patient age, grey-scale ultrasound lesion diameter (<15 or ≥15 mm), distance from the lesion to skin, composition of surrounding tissue (fatty, mixed or dense), and source of referral (screening or symptomatic). Statistical analysis was carried out using the chi-square test. RESULTS: A statistically significant positive association was found between grey-scale ultrasound lesion size and lesion stiffness. Twenty-nine of 70 (41%) lesions ≥15 mm were stiff, versus 10 of 81 (12%) <15 mm (p=0.001). Patient age, distance from the lesion to skin, make-up of surrounding tissue, and source were not significantly associated with stiffness. CONCLUSION: Fibroadenomas giving false-positive SWE results tend to be larger in size than those that do not. More compression of adjacent normal tissue is assumed to be the cause of the present findings. As previous studies have shown that large cancers tend to be stiffer than smaller cancers, it may be appropriate to vary the quantitative cut-off value used for benign/malignant differentiation in SWE according to lesion size.

Magnetic resonance imaging texture analysis classification of primary breast cancer.

OBJECTIVES: Patient-tailored treatments for breast cancer are based on histological and immunohistochemical (IHC) subtypes. Magnetic Resonance Imaging (MRI) texture analysis (TA) may be useful in non-invasive lesion subtype classification. METHODS: Women with newly diagnosed primary breast cancer underwent pre-treatment dynamic contrast-enhanced breast MRI. TA was performed using co-occurrence matrix (COM) features, by creating a model on retrospective training data, then prospectively applying to a test set. Analyses were blinded to breast pathology. Subtype classifications were performed using a cross-validated k-nearest-neighbour (k = 3) technique, with accuracy relative to pathology assessed and receiver operator curve (AUROC) calculated. Mann-Whitney U and Kruskal-Wallis tests were used to assess raw entropy feature values. RESULTS: Histological subtype classifications were similar across training (n = 148 cancers) and test sets (n = 73 lesions) using all COM features (training: 75%, AUROC = 0.816; test: 72.5%, AUROC = 0.823). Entropy features were significantly different between lobular and ductal cancers (p < 0.001; Mann-Whitney U). IHC classifications using COM features were also similar for training and test data (training: 57.2%, AUROC = 0.754; test: 57.0%, AUROC = 0.750). Hormone receptor positive and negative cancers demonstrated significantly different entropy features. Entropy features alone were unable to create a robust classification model. CONCLUSION: Textural differences on contrast-enhanced MR images may reflect underlying lesion subtypes, which merits testing against treatment response. KEY POINTS: • MR-derived entropy features, representing heterogeneity, provide important information on tissue composition. • Entropy features can differentiate between histological and immunohistochemical subtypes of breast cancer. • Differing entropy features between breast cancer subtypes implies differences in lesion heterogeneity. • Texture analysis of breast cancer potentially provides added information for decision making.

Influence of region of interest size and ultrasound lesion size on the performance of 2D shear wave elastography (SWE) in solid breast masses.

AIM: To evaluate the influence of the region of interest (ROI) size and lesion diameter on the diagnostic performance of 2D shear wave elastography (SWE) of solid breast lesions. MATERIALS AND METHODS: A study group of 206 consecutive patients (age range 21-92 years) with 210 solid breast lesions (70 benign, 140 malignant) who underwent core biopsy or surgical excision was evaluated. Lesions were divided into small (diameter <15 mm, n=112) and large lesions (diameter ≥15 mm, n=98). An ROI with a diameter of 1, 2, and 3 mm was positioned over the stiffest part of the lesion. The maximum elasticity (Emax), mean elasticity (Emean) and standard deviation (SD) for each ROI size were compared to the pathological outcome. Statistical analysis was undertaken using the chi-square test and receiver operating characteristic (ROC) analysis. RESULTS: The ROI size used has a significant impact on the performance of Emean and SD but not on Emax. Youden's indices show a correlation with the ROI size and lesion size: generally, the benign/malignant threshold is lower with increasing ROI size but higher with increasing lesion size. CONCLUSIONS: No single SWE parameter has superior performance. Lesion size and ROI size influence diagnostic performance.

Assessment and quantification of sources of variability in breast apparent diffusion coefficient (ADC) measurements at diffusion weighted imaging.

PURPOSE: Apparent Diffusion Coefficient (ADC) measurements are increasingly used for assessing breast cancer response to neoadjuvant chemotherapy although little data exists on ADC measurement reproducibility. The purpose of this work was to investigate and characterise the magnitude of errors in ADC measures that may be encountered in such follow-up studies- namely scanner stability, scan-scan reproducibility, inter- and intra- observer measures and the most reproducible measurement of ADC. METHODS: Institutional Review Board approval was obtained for the prospective study of healthy volunteers and written consent acquired for the retrospective study of patient images. All scanning was performed on a 3.0-T MRI scanner. Scanner stability was assessed using an ice-water phantom weekly for 12 weeks. Inter-scan repeatability was assessed across two scans of 10 healthy volunteers (26-61 years; mean: 44.7 years). Inter- and intra-reader analysis repeatability was measured in 52 carcinomas from clinical patients (29-70 years; mean: 50.0 years) by measuring the whole tumor ADC value on a single slice with maximum tumor diameter (ADCS) and the ADC value of a small region of interest (ROI) on the same slice (ADCmin). Repeatability was assessed using intraclass correlation coefficients (ICC) and coefficients of repeatability (CoR). RESULTS: Scanner stability contributed 6% error to phantom ADC measurements (0.071×10(-3)mm(2)/s; mean ADC=1.089×10(-3)mm(2)/s). The measured scan-scan CoR in the volunteers was 0.122×10(-3)mm(2)/s, contributing an error of 8% to the mean measured values (ADCscan1=1.529×10(-3)mm(2)/s; ADCscan2=1.507×10(-3)mm(2)/s). Technical and clinical observers demonstrated excellent intra-observer repeatability (ICC>0.9). Clinical observer CoR values were marginally better than technical observer measures (ADCS=0.035×10(-3)mm(2)/s vs. 0.097×10(-3)mm(2)/s; ADCmin=0.09×10(-3)mm(2)/s vs. 0.114×10(-3)mm(2)/s). Inter-reader ICC values were good 0.864 (ADCS) and fair 0.677 (ADCmin). Corresponding CoR values were 0.202×10(-3)mm(2)/s and 0.264×10(-3)mm(2)/s, respectively. CONCLUSIONS: Both scanner stability and scan-scan variation have minimal influence on breast ADC measurements, contributing less than 10% error of average measured ADC values. Measurement of ADC values from a small ROI contributes a greater variability in measurements compared with measurement of ADC across the whole visible tumor on one slice. The greatest source of error in follow-up studies is likely to be associated with measures made by multiple observers, and this should be considered where multiple measures are required to assess response to treatment.

Value of shear-wave elastography in the diagnosis of symptomatic invasive lobular breast cancer.

AIM: To investigate the contribution of shear-wave elastography (SWE) in diagnosing invasive lobular breast cancer (ILC) in symptomatic patients. MATERIALS AND METHODS: A retrospective case-controlled study of 52 patients with ILC and 52 patients with invasive ductal cancer (IDC), matched for age and tumour size, was performed. Breast density and mammographic and greyscale ultrasound features were graded using Breast Imaging-Reporting and Data System (BI-RADS) classification by two radiologists, blinded to SWE and pathology findings. Forty-four benign lesions were also included. The sensitivity of SWE was assessed, using a cut-off value of 50 kPa for mean elasticity. Statistical significance was evaluated using Chi-square and Chi-square for trend tests. RESULTS: Mean age for both ILC and IDC groups was 67 years. Mean size for ILC was 44 mm and IDC was 37 mm. The sensitivity for detection of ILC and IDC for mammography, greyscale ultrasound, and SWE were 79% versus 87%, 87% versus 98%, 94% versus 100%, respectively. SWE had significantly higher sensitivities than mammography for the detection of both ILC and IDC (p = 0.012 and p = 0.001, respectively). SWE was not significantly more sensitive than greyscale ultrasound for the detection of either tumour type. Four (8%) lobular cancers were benign/normal at both mammography and greyscale ultrasound, but suspicious on SWE. The incremental gain in sensitivity by using SWE in ILC was statistically significant compared to IDC (p = 0.01). CONCLUSION: SWE can diagnose lobular cancers that have benign/normal findings on conventional imaging as suspicious.

Shear-wave elastography contributes to accurate tumour size estimation when assessing small breast cancers.

AIM: To assess whether the size of peritumoural stiffness (PTS) on shear-wave elastography (SWE) for small primary breast cancers (≤15 mm) was associated with size discrepancies between grey-scale ultrasound (GSUS) and final histological size and whether the addition of PTS size to GSUS size might result in more accurate tumour size estimation when compared to final histological size. MATERIALS AND METHODS: A retrospective analysis of 86 consecutive patients between August 2011 and February 2013 who underwent breast-conserving surgery for tumours of size ≤15 mm at ultrasound was carried out. The size of PTS stiffness was compared to mean GSUS size, mean histological size, and the extent of size discrepancy between GSUS and histology. PTS size and GSUS were combined and compared to the final histological size. RESULTS: PTS of >3 mm was associated with a larger mean final histological size (16 versus 11.3 mm, p < 0.001). PTS size of >3 mm was associated with a higher frequency of underestimation of final histological size by GSUS of >5 mm (63% versus 18%, p < 0.001). The combination of PTS and GSUS size led to accurate estimation of the final histological size (p = 0.03). The size of PTS was not associated with margin involvement (p = 0.27). CONCLUSION: PTS extending beyond 3 mm from the grey-scale abnormality is significantly associated with underestimation of tumour size of >5 mm for small invasive breast cancers. Taking into account the size of PTS also led to accurate estimation of the final histological size. Further studies are required to assess the relationship of the extent of SWE stiffness and margin status.

Accuracy of non-operative identification of the sentinel lymph node using combined gamma and ultrasound scanning.

AIM: To assess how accurately the sentinel lymph node (SLN) can be identified percutaneously, using gamma probe and ultrasound technology. MATERIALS AND METHODS: Women with breast cancer, scheduled for wide local excision or mastectomy with SLN biopsy (SLNB), were included. Peri-areolar intradermal injection of technetium-99 nanocolloid was performed on the morning of surgery and 1-2 ml of blue dye was injected in the peri-areolar region once the patient was anaesthetized. Prior to surgery, a gamma probe was used over the skin to identify any hot spot that could represent a SLN. Ultrasound, guided by the hot spot, was then used to visualize potential SLNs and guide the insertion of a localizing wire. The accuracy in localizing the SLN by preoperative gamma-probe guided ultrasonography was assessed by comparison to SLNB. RESULTS: A SLN was correctly identified and marked using gamma-probe guided ultrasonography in 44 of 59 cases (75%; 95% CI: 63-86%). CONCLUSION: This study supports the case for investigating percutaneous gamma probe and ultrasound guided interventions in the axilla in women with breast cancer, as a potential alternative to surgical SLNB.