Deep Learning-Based Segmentation of Locally Advanced Breast Cancer on MRI in Relation to Residual Cancer Burden: A Multi-Institutional Cohort Study.

BACKGROUND: While several methods have been proposed for automated assessment of breast-cancer response to neoadjuvant chemotherapy on breast MRI, limited information is available about their performance across multiple institutions. PURPOSE: To assess the value and robustness of deep learning-derived volumes of locally advanced breast cancer (LABC) on MRI to infer the presence of residual disease after neoadjuvant chemotherapy. STUDY TYPE: Retrospective. SUBJECTS: Training cohort: 102 consecutive female patients with LABC scheduled for neoadjuvant chemotherapy (NAC) from a single institution (age: 25-73 years). Independent testing cohort: 55 consecutive female patients with LABC from four institutions (age: 25-72 years). FIELD STRENGTH/SEQUENCE: Training cohort: single vendor 1.5 T or 3.0 T. Testing cohort: multivendor 3.0 T. Gradient echo dynamic contrast-enhanced sequences. ASSESSMENT: A convolutional neural network (nnU-Net) was trained to segment LABC. Based on resulting tumor volumes, an extremely randomized tree model was trained to assess residual cancer burden (RCB)-0/I vs. RCB-II/III. An independent model was developed using functional tumor volume (FTV). Models were tested on an independent testing cohort and response assessment performance and robustness across multiple institutions were assessed. STATISTICAL TESTS: The receiver operating characteristic (ROC) was used to calculate the area under the ROC curve (AUC). DeLong's method was used to compare AUCs. Correlations were calculated using Pearson's method. P values <0.05 were considered significant. RESULTS: Automated segmentation resulted in a median (interquartile range [IQR]) Dice score of 0.87 (0.62-0.93), with similar volumetric measurements (R = 0.95, P < 0.05). Automated volumetric measurements were significantly correlated with FTV (R = 0.80). Tumor volume-derived from deep learning of DCE-MRI was associated with RCB, yielding an AUC of 0.76 to discriminate between RCB-0/I and RCB-II/III, performing similar to the FTV-based model (AUC = 0.77, P = 0.66). Performance was comparable across institutions (IQR AUC: 0.71-0.84). DATA CONCLUSION: Deep learning-based segmentation estimates changes in tumor load on DCE-MRI that are associated with RCB after NAC and is robust against variations between institutions. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 4.

2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab.

BACKGROUND: We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer. METHODS: HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab. RESULTS: Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson's r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11-2.93; p = 0.016; explained variance 0.34). CONCLUSIONS: Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.

Changes in body composition and muscle attenuation during taxane-based chemotherapy in patients with metastatic breast cancer.

PURPOSE: Body composition parameters including low muscle mass, muscle attenuation (which reflects muscle quality) and adipose tissue measurements have emerged as prognostic factors in cancer patients. However, knowledge regarding the possibility of excessive muscle loss during specific systemic therapies is unknown. We describe the changes in body composition and muscle attenuation (MA) during taxane- and anthracycline-based regimens and its association with overall survival (OS) in metastatic breast cancer patients. METHODS: The lumbar skeletal muscle index (LSMI) was used as marker of muscle mass. LSMI, MA, subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intramuscular adipose tissue (IMAT) were measured before and after first-line treatment with paclitaxel (n = 73) or 5-fluorouracil-doxorubicin-cyclophosphamide (FAC) (n = 25) using CT-images. Determinants of the change of LSMI and MA were analyzed using multiple linear regression. OS was assessed using Cox proportional hazard models. RESULTS: MA significantly decreased during paclitaxel treatment (- 0.9 HU, p = 0.03). LSMI (p = 0.40), SAT (p = 0.75), VAT (p = 0.84) and IMAT (p = 0.10) remained stable. No significant alterations in body composition parameters during FAC-treatment were observed. Previous (neo-)adjuvant chemotherapy contributed to larger loss of MA during the current treatment. Body composition changes during chemotherapy were not associated with OS. CONCLUSIONS: MA decreased during treatment with paclitaxel, while muscle mass was stable. Body composition changes are not associated with survival in the absence of progressive disease.

Severe sarcopenia might be associated with a decline of physical independence in older patients undergoing chemotherapeutic treatment.

PURPOSE: Assessing physical reserve in older cancer patients before treatment decision-making remains challenging. The maintenance of physical independence during therapy is sometimes just as important for these patients as oncological outcomes. Recently, sarcopenia has been recognized as a possible important prognostic factor for outcome in cancer patients. We investigated the association between different levels of sarcopenia and the decline of physical independence during chemotherapy in older cancer patients (≥ 65 years). METHODS: Sarcopenia was divided into presarcopenia, sarcopenia, and severe sarcopenia according to an international consensus and was related to physical independence determined by measuring instrumental activities of daily living (IADL), using binary logistic regression models. CT-based muscle mass is necessary to diagnose sarcopenia and was related to five functional tests, in order to investigate whether these easy-to-perform tests could replace the more invasive CT-based muscle measurement. RESULTS: A total of 131 patients were included (median age 72 years). The prevalence of presarcopenia, sarcopenia, and severe sarcopenia was 47.7, 18.5, and 7.7%, respectively. Compared to no sarcopenia, only severe sarcopenia seemed associated with a decline of physical independence after chemotherapy (OR 5.95, 95% CI 0.76-46.48). Muscle mass was only significantly associated with muscle strength, but not with tests measuring physical function. CONCLUSION: The level of sarcopenia might be a useful tool in addition to routine oncological assessment to identify older cancer patients with increased risk of physical decline after chemotherapy.

Brachial Artery Thrombosis as a Presentation of Non-Small Cell Pulmonary Carcinoma Growing Into the Left Atrium.

We present a case of a thrombus in the left brachial artery as a cardioembolic presentation of pulmonary carcinoma. There have been few reports describing this clinical presentation, but if present, prognosis is very poor. Therefore, a cardioembolic event should be borne in mind as an atypical presentation of pulmonary carcinoma. (Level of Difficulty: Beginner.).

Ten years follow-up of histologically benign calcifications in the breast after vacuum-assisted stereotactic biopsy (VASB): Is additional mammographic follow-up warranted?

OBJECTIVE: This study assessed the short-term and the long-term breast cancer rate in patients with benign histopathologic results after a vacuum-assisted stereotactic biopsy (VASB) for calcifications. METHODS: In a retrospective cohort study, all consecutive patients who had a benign diagnosis after VASB to analyze breast calcifications. Data of breast cancer development at short-term (four years) and long-term follow-up was gathered. Breast cancer rates in our cohort were compared to the breast cancer incidence in the general population. RESULTS: Of 1376 patients who underwent VASB to analyze breast calcifications, 823 had a benign histopathologic diagnosis. During short-term follow-up, eight patients developed breast cancer. During the mean long-term follow-up period of 9.3 ± 3.1 years, 22 patients were diagnosed with ipsilateral breast cancer. The incidence rate of breast cancer after benign biopsy was comparable to the rate in the general population. CONCLUSION: In patients with VASB-confirmed benign calcifications of the breast, we found no excess incidence of ipsilateral breast cancer during ten years follow-up. Therefore, in patients with an increased risk of breast cancer (due to a history of breast cancer or familial risk) annual mammography should be sufficient. Patients with a population-based risk may be monitored via biennial mammography by the national screening program. More frequent screening would provide no benefit.

Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.

BACKGROUND: Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). PATIENTS AND METHODS: A skeletal muscle index (SMI) in cm2/m2 and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm2/m2), sarcopenic obesity (LMM and BMI ≥30 kg/m2) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT. RESULTS: The prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34-3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14-2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA. CONCLUSION: LMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice.

Multiparametric MRI With Dynamic Contrast Enhancement, Diffusion-Weighted Imaging, and 31-Phosphorus Spectroscopy at 7 T for Characterization of Breast Cancer.

OBJECTIVES: To describe and to correlate tumor characteristics on multiparametric 7 tesla (T) breast magnetic resonance imaging (MRI) with prognostic characteristics from postoperative histopathology in patients with breast cancer. MATERIALS AND METHODS: Institutional review board approval and written informed consent of 15 women (46-70 years) with 17 malignant lesions were obtained. In this prospective study (March 2013 to March 2014), women were preoperatively scanned using dynamic contrast-enhanced MRI, diffusion-weighted imaging, and 31-phosphorus spectroscopy (¹³P-MRS). The value of the protocol was assessed to quantify tumor differentiation and proliferation. Dynamic contrast-enhanced MRI was assessed according to the American College of Radiology Breast Imaging Reporting and Data System-MRI lexicon. Apparent diffusion coefficients (ADCs) were calculated from diffusion-weighted imaging. On ¹³P-MRS, at the location of the tumor, the amount of phosphorus components was obtained in a localized spectrum. In this spectrum, the height of phosphodiester (PDE) and phosphomonoester (PME) peaks was assessed to serve as a measure for metabolic activity, stratifying tumors into a PDE > PME, PDE = PME, or PDE < PME group. Tumor grade and mitotic count from resection specimen were compared with the MRI characteristics using explorative analyses. RESULTS: On dynamic contrast-enhanced MRI, the mean tumor size was 24 mm (range, 6-55 mm). An inverse trend was seen between ADC and tumor grade (P = 0.083), with mean ADC of 867 × 10⁻6 mm²/s for grade 1 (N = 4), 751 × 10⁻6 mm²/s for grade 2 (N = 6), and 659 × 10⁻6 mm²/s for grade 3 (N = 2) tumors. Between P-MR spectra and mitotic count, a relative increase of PME over PDE showed significant association with increasing mitotic counts (P = 0.02); a mean mitotic count of 6 was found in the PDE greater than PME group (N = 7), 8 in the PDE = PME group (N = 1), and 17 in the PDE < PME group (N = 3). CONCLUSIONS: Multiparametric 7 T breast MRI is feasible in clinical setting and shows association between ADC and tumor grade, and between ¹³P-MRS and mitotic count.

Lower extremity arterial disease: multidetector CT angiography meta-analysis.

PURPOSE: To obtain the best available estimates of the diagnostic performance of multidetector computed tomographic (CT) angiography compared with that of digital subtraction angiography (DSA) in the assessment of symptomatic lower extremity arterial disease and to identify the most important sources of variation in diagnostic performance between studies. MATERIALS AND METHODS: Reports of studies published from January 2000 through April 2006 in English, German, French, or Spanish were searched for by using the MEDLINE, EMBASE, and Cochrane databases. Studies were included if they allowed construction of 2 x 2 contingency tables for the detection of stenosis of 50% or greater at multidetector CT angiography compared with that at DSA -- the reference standard -- in patients with claudication or critical ischemia. Two observers extracted data about study design, patient characteristics, arterial tracts, and technical protocols. Random-effects summary receiver operating characteristic analysis was performed to examine the influence of these data on diagnostic performance. RESULTS: Of the 70 studies initially identified, 12 were included in which multidetector CT angiography was used to evaluate 9541 arterial segments in 436 patients. The pooled sensitivity and specificity for detecting a stenosis of at least 50% per segment were 92% (95% confidence interval: 89%, 95%) and 93% (95% confidence interval: 91%, 95%), respectively. Three studies provided data about the diagnostic performance of multidetector CT angiography in subdivisions of the arterial tract. The diagnostic performance of multidetector CT angiography in the infrapopliteal tract was lower than but not significantly different from that in the aortoiliac (P > .11) and femoropopliteal (P > .40) tracts. Regression analysis showed that diagnostic performance was not significantly influenced by differences in study characteristics. CONCLUSION: Multidetector CT angiography is an accurate diagnostic test in the assessment of arterial disease (> or =50% stenosis) of the entire lower extremity.

Multi-detector row computed tomography angiography of peripheral arterial disease.

With the introduction of multi-detector row computed tomography (MDCT), scan speed and image quality has improved considerably. Since the longitudinal coverage is no longer a limitation, multi-detector row computed tomography angiography (MDCTA) is increasingly used to depict the peripheral arterial runoff. Hence, it is important to know the advantages and limitations of this new non-invasive alternative for the reference test, digital subtraction angiography. Optimization of the acquisition parameters and the contrast delivery is important to achieve a reliable enhancement of the entire arterial runoff in patients with peripheral arterial disease (PAD) using fast CT scanners. The purpose of this review is to discuss the different scanning and injection protocols using 4-, 16-, and 64-detector row CT scanners, to propose effective methods to evaluate and to present large data sets, to discuss its clinical value and major limitations, and to review the literature on the validity, reliability, and cost-effectiveness of multi-detector row CT in the evaluation of PAD.

Vessel wall calcifications at multi-detector row CT angiography in patients with peripheral arterial disease: effect on clinical utility and clinical predictors.

PURPOSE: To evaluate retrospectively the effect of vessel wall calcifications on the clinical utility of multi-detector row computed tomographic (CT) angiography performed in patients with peripheral arterial disease and to identify clinical predictors for the presence of vessel wall calcifications. MATERIALS AND METHODS: The study was approved by the hospital institutional review board, and informed consent was obtained from all patients. For this study the authors included patients from two randomized controlled trials that measured the costs and effects of diagnostic imaging in patients with peripheral arterial disease. All patients underwent CT angiography and were followed up for 6 months. Clinical utility was measured on the basis of therapeutic confidence (rated on a 10-point scale) in the results of initial CT angiography and the need for additional vascular imaging. Univariable and multivariable logistic and linear regression analysis and the area under the receiver operating characteristic curve were used to evaluate the effect of vessel wall calcifications on the clinical utility of CT angiography and the use of patient characteristics to predict the number of calcified segments at CT angiography. RESULTS: A total of 145 patients were included (mean age, 64 years; 70% men). The authors found that the number of calcified segments was a significant predictor of the need for additional imaging (P = .001) and of the confidence scores (P < .001). The number of calcified segments discriminated between patients who required additional imaging after CT angiography and those who did not (area under the receiver operating characteristic curve, 0.66; 95% confidence interval: 0.54, 0.77). Age, diabetes mellitus, and cardiac disease were significant predictors of the number of calcified segments in both the univariable and multivariable analyses (P < .05). CONCLUSION: Vessel wall calcifications decrease the clinical utility of CT angiography in patients with peripheral arterial disease. Diabetes mellitus, cardiac disease, and elderly age (older than 84 years) are independently predictive for the presence of vessel wall calcifications.

Interobserver agreement for the interpretation of contrast-enhanced 3D MR angiography and MDCT angiography in peripheral arterial disease.

OBJECTIVE: The objective of our study was to compare interobserver agreement for interpretations of contrast-enhanced 3D MR angiography and MDCT angiography in patients with peripheral arterial disease. SUBJECTS AND METHODS: Of 226 eligible patients, 69 were excluded. The remaining 157 consecutive patients were prospectively randomized to either MR angiography (n = 78) or MDCT angiography (n = 79). Two observers independently evaluated for arterial stenosis or occlusion on MR angiography (2,157 segments) and MDCT angiography (2,419 segments) using a 5-point ordinal scale. Vessel wall calcifications were noted. Interobserver agreement for each technique was evaluated with a weighted kappa (kappa(w)) statistic. RESULTS: Although interobserver agreement for both was excellent, the interobserver agreement for MR angiography (kappa(w) = 0.90; 95% confidence interval [CI], 0.89-0.92) was higher than that for MDCT angiography (kappa(w) = 0.85; 95% CI, 0.83-0.86) for reporting the degree of arterial stenosis or occlusion in all segments. For the different anatomic locations, the interobserver agreement for MR angiography versus MDCT angiography was as follows: aortoiliac (kappa(w) =0.91 vs 0.84, respectively), femoropopliteal (kappa(w) = 0.91 vs 0.87), and crural (kappa(w) = 0.90 vs 0.83) segments. The interobserver agreement of MDCT angiography significantly decreased in the presence of calcifications but was still good for all anatomic locations. The lowest agreement was found for crural segments in the presence of calcifications (kappa(w) = 0.67). With MR angiography, there were 12 times more nondiagnostic segments than with MDCT angiography (81 vs 7, respectively). CONCLUSION: Interpretations of MR angiography and MDCT angiography for peripheral arterial disease have an excellent interobserver agreement. MR angiography has a higher interobserver agreement than MDCT angiography, and the presence of calcified segments significantly decreases interobserver agreement for MDCT angiography.

DSA versus multi-detector row CT angiography in peripheral arterial disease: randomized controlled trial.

PURPOSE: To prospectively compare therapeutic confidence in, patient outcomes (in terms of quality of life) after, and the costs of digital subtraction angiography (DSA) with those of multi-detector row computed tomographic (CT) angiography as the initial diagnostic imaging test in patients with peripheral arterial disease (PAD). MATERIALS AND METHODS: Institutional medical ethics committee approval and patient informed consent were obtained. Between April 2000 and August 2001, patients with PAD were randomly assigned to undergo either DSA or multi-detector row CT angiography as the initial diagnostic imaging test. Outcomes were the therapeutic confidence assessed by physicians (on a scale from 0 to 10), the need for additional imaging, the health-related quality of life at 6-month follow-up, diagnostic and therapeutic costs, and the costs for a hospital stay. Costs were computed from a hospital perspective according to Dutch guidelines for cost calculations in health care. Mean outcomes were compared between groups with unpaired t testing and were adjusted for predictive baseline characteristics with multivariable regression analysis. RESULTS: Among the 145 patients, 72 were randomly allocated to the DSA group and 73 to the CT angiography group. One patient in the DSA group had to be excluded. Mean age was 63 years in the DSA group and 64 years in the CT angiography group. There were 47 men in the DSA group and 58 men in the CT angiography group. Physician confidence in making a correct therapeutic choice was significantly higher at DSA (mean confidence score, 8.2) than at CT angiography (mean score, 7.2; P < .001). During 6-month follow-up, 14% less additional imaging was performed in the DSA group than in the CT angiography group (P = .3). No significant quality-of-life differences were found between groups. The diagnostic cost associated with DSA (564 +/- 210 euro [standard deviation]) was significantly higher than that associated with CT angiography (363 +/- 273 euro), a difference of -201 euro (95% confidence interval: -281 euro, -120 euro; P < .001). Therapeutic and hospitalization costs were similar for both strategies. CONCLUSION: These results suggest that use of noninvasive multi-detector row CT angiography instead of DSA as the initial diagnostic imaging test for PAD provides sufficient information for therapeutic decision making and reduces imaging costs.

Contrast-enhanced MR angiography and digital subtraction angiography in living renal donors: diagnostic agreement, impact on decision making, and costs.

OBJECTIVE: The objective of our study was to evaluate the diagnostic agreement, the impact on decision making, and the costs of contrast-enhanced MR angiography and digital subtraction angiography in the workup of living renal donors. CONCLUSION: Contrast-enhanced MR angiography for the preoperative evaluation of renal donors is superior to digital subtraction angiography in revealing vascular anomalies and depicting parenchymal abnormalities and is less costly; furthermore, it does not lead to preoperative decisions that differ from those based on digital subtraction angiography. If contrast-enhanced MR angiography does not provide sufficient information to make a confident decision, an additional digital subtraction angiography examination should be performed.