The aim was to investigate whether pathologic complete response (pCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with ...neoadjuvant systemic therapy (NST) for different breast cancer subtypes.
Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast pCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.
Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pathologic response of the primary tumor with associated pathologic axillary outcome. Multivariable analysis was performed to determine clinicopathological variables correlated with ypN0.
A total of 4084 patients were included for analyses, of whom 986 (24.1%) achieved breast pCR. In clinically node negative patients (cN0), 97.7% (432/442) with breast pCR had ypN0 compared with 71.6% (882/1232) without breast pCR (P < 0.001). In clinically node positive patients (cN1), 45.0% (245/544) with breast pCR had ypN0 compared with 9.4% (176/1866) without breast pCR (P < 0.001). The odds of ypN0 was decreased in case of clinical T3 stage (OR 0.59, 95% CI 0.40-0.87), cN1 (OR 0.03, 95% CI 0.02-0.04) and ER+HER2- subtype (OR 0.30, 95% CI 0.20-0.44), and increased in case of breast pCR (OR 4.53, 95% CI 3.27-6.28).
Breast pCR achieved after NST is strongly correlated with ypN0 in cN0 patients, especially in ER+HER2+, ER-HER2+, and triple negative subtypes. These results provide data to proceed with future clinical trials to investigate if axillary surgery can be safely omitted in these selected patients when image-guided tissue sampling identifies a breast pCR.
Objectives
To investigate whether breast MRI has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer.
Methods
Forty-seven ...patients were included. All had undergone both breast MRI and dedicated axillary MRI, followed by surgery. All included breast MRI exams had complete field of view (FOV) of the axillary region. First, unenhanced T2-weighted (T2W) and subsequent diffusion-weighted (DW) images of both MRI exams were independently analyzed by two breast radiologists using a confidence scale and compared to histopathology. ADC values were measured by two researchers independently. Diagnostic performance parameters were calculated on a patient-by-patient basis.
Results
T2W breast MRI had the following diagnostic performance: sensitivity of 50.0% and 62.5%, specificity of 92.3%, PPV of 57.1% and 62.5%, NPV of 90.0% and 92.3%, and AUC of 0.72 for reader 1 and 0.78 for reader 2. T2W dedicated axillary MRI had the following diagnostic performance: sensitivity of 37.5% and 62.5%, specificity of 82.1% and 92.3%, PPV of 44.6% and 50.0%, NPV of 87.8% and 91.4%, and AUC of 0.65 for reader 1 and 0.73 for reader 2. In both evaluations, addition of DW images resulted in comparable diagnostic performance. For both breast MRI and dedicated axillary MRI, there was no significant difference between mean ADC values of benign and malignant lymph nodes.
Conclusions
T2W breast MRI with complete FOV of the axillary region has comparable diagnostic performance as T2W dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Optimization of T2W breast MRI protocol by including a complete FOV of the axillary region can, therefore, be recommended in clinical practice.
Key Points
• Breast MRI with complete field of view of the axillary region has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer.
• Optimization of breast MRI protocol by including a complete field of view of the axillary region is recommended in clinical practice.
• For both breast MRI and dedicated axillary MRI, DW imaging (including ADC measurements) is of no added value.
This retrospective study investigated the value of pretreatment contrast-enhanced Magnetic Resonance Imaging (MRI)-based radiomics for the prediction of pathologic complete tumor response to ...neoadjuvant systemic therapy in breast cancer patients. A total of 292 breast cancer patients, with 320 tumors, who were treated with neo-adjuvant systemic therapy and underwent a pretreatment MRI exam were enrolled. As the data were collected in two different hospitals with five different MRI scanners and varying acquisition protocols, three different strategies to split training and validation datasets were used. Radiomics, clinical, and combined models were developed using random forest classifiers in each strategy. The analysis of radiomics features had no added value in predicting pathologic complete tumor response to neoadjuvant systemic therapy in breast cancer patients compared with the clinical models, nor did the combined models perform significantly better than the clinical models. Further, the radiomics features selected for the models and their performance differed with and within the different strategies. Due to previous and current work, we tentatively attribute the lack of improvement in clinical models following the addition of radiomics to the effects of variations in acquisition and reconstruction parameters. The lack of reproducibility data (i.e., test-retest or similar) meant that this effect could not be analyzed. These results indicate the need for reproducibility studies to preselect reproducible features in order to properly assess the potential of radiomics.
Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph ...node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51-68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41-0.74 and 0.48-0.89 in the training cohorts, respectively, and between 0.30-0.98 and 0.37-0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.
This study sought to assess the association of baseline left atrial (LA) phasic function measured with cardia magnetic resonance (CMR) and incident ischemic cerebrovascular events (CVE).
LA ...remodeling is a known predictor of atrial fibrillation (AF), which is a risk factor for ischemic CVE. Despite studies showing an association between LA remodeling and ischemic CVE, the association of LA mechanical function with ischemic CVE in a population free of known cardiovascular disease is not fully studied.
Phasic LA volumes; total, passive, and active LA emptying fractions (LAEF); and peak longitudinal LA strain were measured using feature-tracking CMR in 4,261 MESA (Multi-Ethnic Study of Atherosclerosis) participants (61 ± 10 years of age; 48% male). All individuals were free of clinical cardiovascular disease at baseline. Participants were followed for 11.6 ± 3.5 years for the diagnosis of incident ischemic CVE, defined as ischemic stroke or transient ischemic attack adjudicated by vascular neurologists.
During the follow-up, 193 (1.26 per 1,000 person-years) ischemic CVE (134 ischemic strokes and 59 TIAs) occurred. Individuals with incident ischemic CVE had larger LA volumes and lower passive, active, and total LAEFs at baseline. In multivariate analysis adjusted for known CVE risk factors, left ventricular mass and interim AF, total LAEF was associated with incident ischemic CVE (hazard ratio HR: 0.85 per SD; 95% confidence interval CI: 0.74 to 0.98; p = 0.027). The unadjusted HR for the lowest tertile of total LAEF compared to the highest tertile was 2.0 (95% CI: 1.43 to 2.79; p < 0.001), and the adjusted HR was 1.47 (95% CI: 1.04 to 2.05; p = 0.031). Addition of total LAEF to known clinical risk factors of CVE and left ventricular mass resulted in an improved predictive accuracy (C statistic of 0.76 vs. 0.73, respectively; p = 0.039).
Reduced total LAEF was associated with incident ischemic CVE independent of known cerebrovascular risk factors and incident AF. Assessment of LA function may add further information in stratifying asymptomatic individuals at risk for ischemic stroke.
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An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is ...lacking.
To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease.
The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies.
Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy).
Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype.
The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease.
This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy.
The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.
Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the benefits still remain controversial. This ...meta-analysis aims to evaluate the efficacy of bone marrow-derived mononuclear cell (BMMNC) therapy in patients with acute myocardial infarction, but also explores the effect of newer generations of stem cells.
A random-effects meta-analysis was performed on randomized controlled trials investigating the effects of stem cell therapy in patients with acute myocardial infarction that were published between January 2002 and September 2013. The defined end points were left ventricular (LV) ejection fraction, LV end-systolic and end-diastolic volumes, infarct size, and major adverse cardiac and cerebrovascular event rates. Also, several subgroup analyses were performed on BMMNC trials. Overall, combining the results of 22 randomized controlled trials (RCTs), LV ejection fraction increased by +2.10% (95% confidence interval CI, 0.68-3.52; P=0.004) in the BMMNC group as compared with controls, evoked by a preservation of LV end-systolic volume (-4.05 mL; 95% CI, -6.91 to -1.18; P=0.006) and a reduction in infarct size (-2.69%; 95% CI, -4.83 to -0.56; P=0.01). However, there is no effect on cardiac function, volumes, or infarct size, when only RCTs (n=9) that used MRI-derived end points were analyzed. Moreover, no beneficial effect could be detected on major adverse cardiac and cerebrovascular event rates after BMMNC infusion after a median follow-up duration of 6 months.
Intracoronary infusion of BMMNC is safe, but does not enhance cardiac function on MRI-derived parameters, nor does it improve clinical outcome. New and possibly more potent stem cells are emerging in the field, but their clinical efficacy still needs to be defined in future trials.
The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response ...after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients.
NST can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management.
PubMed and Embase were searched for studies that compared noninvasive imaging after NST with axillary surgery outcome to identify axillary response in patients with initial pathologically proven axillary lymph node metastasis. Two reviewers independently screened the studies and extracted the data. A meta-analysis was performed by computing the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Thirteen studies describing 2380 patients were included for final analysis. Of these patients, 1322 had undergone axillary ultrasound, 849 breast MRI, and 209 whole-body 18F-FDG PET-CT. The overall axillary pathologic complete response rate was 39.5% (941/2380). For axillary ultrasound, the pooled sensitivity, specificity, PPV, and NPV were 65%, 69%, 77%, 50%, respectively. For breast MRI, the pooled sensitivity, specificity, PPV, and NPV were 60%, 76%, 78%, 58%, respectively. For whole-body 18F-FDG PET-CT, the pooled sensitivity, specificity, PPV, and NPV were 38%, 86%, 78%, 49%, respectively.
The diagnostic performance of current noninvasive imaging modalities is limited to accurately assess axillary response after NST in clinically node-positive breast cancer patients.
This study sought to assess the association of baseline left atrial (LA) phasic function measured with cardia magnetic resonance (CMR) and incident ischemic cerebrovascular events (CVE).
LA ...remodeling is a known predictor of atrial fibrillation (AF), which is a risk factor for ischemic CVE. Despite studies showing an association between LA remodeling and ischemic CVE, the association of LA mechanical function with ischemic CVE in a population free of known cardiovascular disease is not fully studied.
Phasic LA volumes; total, passive, and active LA emptying fractions (LAEF); and peak longitudinal LA strain were measured using feature-tracking CMR in 4,261 MESA (Multi-Ethnic Study of Atherosclerosis) participants (61 ± 10 years of age; 48% male). All individuals were free of clinical cardiovascular disease at baseline. Participants were followed for 11.6 ± 3.5 years for the diagnosis of incident ischemic CVE, defined as ischemic stroke or transient ischemic attack adjudicated by vascular neurologists.
During the follow-up, 193 (1.26 per 1,000 person-years) ischemic CVE (134 ischemic strokes and 59 TIAs) occurred. Individuals with incident ischemic CVE had larger LA volumes and lower passive, active, and total LAEFs at baseline. In multivariate analysis adjusted for known CVE risk factors, left ventricular mass and interim AF, total LAEF was associated with incident ischemic CVE (hazard ratio HR: 0.85 per SD; 95% confidence interval CI: 0.74 to 0.98; p = 0.027). The unadjusted HR for the lowest tertile of total LAEF compared to the highest tertile was 2.0 (95% CI: 1.43 to 2.79; p < 0.001), and the adjusted HR was 1.47 (95% CI: 1.04 to 2.05; p = 0.031). Addition of total LAEF to known clinical risk factors of CVE and left ventricular mass resulted in an improved predictive accuracy (C statistic of 0.76 vs. 0.73, respectively; p = 0.039).
Reduced total LAEF was associated with incident ischemic CVE independent of known cerebrovascular risk factors and incident AF. Assessment of LA function may add further information in stratifying asymptomatic individuals at risk for ischemic stroke.
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