Performance of Screening Breast MRI After Negative Full-Field Digital Mammography Versus After Negative Digital Breast Tomosynthesis in Women at Higher Than Average Risk for Breast Cancer.

OBJECTIVE: The objective of our study was to compare the supplemental cancer yield and performance of breast MRI in women at higher-than-average risk for breast cancer after negative 2D full-field digital mammography (FFDM) or negative digital breast tomosynthesis (DBT). MATERIALS AND METHODS: Retrospective review identified 4418 screening breast MRI examinations: 2291 were performed from January 2010 through January 2012 of patients with a negative FFDM examination in the 12 months before MRI (FFDM group), and 2127 were performed from January 2013 through January 2015 of patients with a negative DBT examination in the 12 months before MRI (DBT group). Screening indications included genetic predisposition, personal history of breast cancer or high-risk lesion, prior chest irradiation, family history, or other risk factors conferring a lifetime risk of greater than 20%. Supplemental cancer detection rate (CDR), abnormal interpretation rate (AIR), and positive predictive values (PPVs) were estimated with 95% exact CIs. Logistic regression analysis, adjusting for differences in patient demographics, was used to compare metrics. RESULTS: There was no significant difference in the CDR of MRI in the FFDM group versus the DBT group (11 vs 16 cancers per 1000 examinations, respectively; odds ratio, 1.4; 95% CI, 0.4-1.2; p = 0.23). The AIR, PPV1, PPV2, and PPV3 were 7.4%, 15%, 23%, and 28% for the FFDM group and 7.3%, 22%, 33%, and 35% for the DBT group, with no statistical differences. Of the cancers detected in both groups, the majority were invasive, less than 1 cm, and node-negative. CONCLUSION: In women at higher-than-average risk of breast cancer screened with DBT, the supplemental CDR of MRI is similar to that of MRI after FFDM screening, with most cancers being invasive, subcentimeter, and node-negative.

Repeat CT Performed Within One Month of CT Conducted in the Emergency Department for Abdominal Pain: A Secondary Analysis of Data From a Prospective Multicenter Study.

OBJECTIVE: The purpose of this study is to determine both the frequency of repeat CT performed within 1 month after a patient visits the emergency department (ED) and undergoes CT evaluation for abdominal pain and the frequency of worsened or new CT-based diagnoses. SUBJECTS AND METHODS: Secondary analysis was performed on data collected during a prospective multicenter study. The parent study included patients who underwent CT in the ED for abdominal pain between 2012 and 2014, and these patients constituted the study group of the present analysis. The proportion of patients who underwent (in any setting) repeat abdominal CT within 1 month of the index CT examination was calculated. For each of these patients, results of the index and repeat CT scans were compared by an independent panel and categorized as follows: no change (group 1); same process, improved (group 2); same process, worse (group 3); or different process (group 4). The proportion of patients in groups 1 and 2 versus groups 3 and 4 was calculated, and patient and ED physician characteristics were compared. RESULTS: The parent study included 544 patients (246 of whom were men [45%]; mean patient age, 49.4 years). Of those 544 patients, 53 (10%; 95% CI, 7.5-13%) underwent repeat abdominal CT. Patients' CT comparisons were categorized as follows: group 1 for 43% of patients (23/53), group 2 for 26% (14/53), group 3 for 15% (8/53), and group 4 for 15% (8/53). New or worse findings were present in 30% of patients (16/53) (95% CI, 19-44%). When patients with findings in groups 1 and 2 were compared to patients with findings in groups 3 and 4, no significant difference was noted in patient age (p = 0.25) or sex (p = 0.76), the number of days between scans (p = 0.98), and the diagnostic confidence of the ED physician after the index CT scan was obtained (p = 0.33). CONCLUSION: Short-term, repeat abdominal CT was performed for 10% of patients who underwent CT in the ED for abdominal pain, and it yielded new or worse findings for 30% of those patients.

Predictors of surveillance mammography outcomes in women with a personal history of breast cancer.

PURPOSE: To identify predictors of poor mammography surveillance outcomes based on clinico-pathologic features. METHODS: This study was HIPAA compliant and IRB approved. We performed an electronic medical record review for a cohort of women with American Joint Committee on Cancer (AJCC) Stage I or II invasive breast cancer treated with breast conservation therapy who developed subsequent in-breast treatment recurrence (IBTR) or contralateral breast cancer (CBC). Poor surveillance outcome was defined as second breast cancer not detected by surveillance mammography, including interval cancers (diagnosed within 365 days of surveillance mammogram with negative results) and clinically detected cancers (diagnosed without a surveillance mammogram in the preceding 365 days). Univariate and multivariate logistic regression were performed to identify predictors of poor mammography surveillance outcome, including patient and primary tumor characteristics, breast density, mode of primary tumor detection, and time to second cancer diagnosis. RESULTS: 164 women met inclusion criteria (65 with IBTR, 99 with CBC); 124 had screen-detected second cancers. On univariate analysis, poor surveillance outcome (n = 40) was associated with age at primary cancer diagnosis < 50 years (p < 0.0001), AJCC stage II primary cancers (p = 0.007), and heterogeneously or extremely dense breasts (p = 0.04). On multivariate analysis, age < 50 years at primary breast cancer diagnosis remained a significant predictor of poor surveillance outcome (p = 0.001). CONCLUSION: Women younger than age 50 at primary breast cancer diagnosis are at risk of poor surveillance mammography outcomes, and may be appropriate candidates for more intensive clinical and imaging surveillance.

Role of CT in the Diagnosis of Nonspecific Abdominal Pain: A Multicenter Analysis.

OBJECTIVE: The objective of our study was to determine whether specific patient and physician factors-known before CT-are associated with a diagnosis of nonspecific abdominal pain (NSAP) after CT in the emergency department (ED). MATERIALS AND METHODS: We analyzed data originally collected in a prospective multicenter study. In the parent study, we identified ED patients referred to CT for evaluation of abdominal pain. We surveyed their physicians before and after CT to identify changes in leading diagnoses, diagnostic confidence, and admission decisions. In the current study, we conducted a multiple regression analysis to identify whether the following were associated with a post-CT diagnosis of NSAP: patient age; patient sex; physicians' years of experience; physicians' pre-CT diagnostic confidence; and physicians' pre-CT admission decision if CT had not been available. We analyzed patients with and those without a pre-CT diagnosis of NSAP separately. For the sensitivity analysis, we excluded patients with different physicians before and after CT. RESULTS: In total, 544 patients were included: 10% (52/544) with a pre-CT diagnosis of NSAP and 90% (492/544) with a pre-CT diagnosis other than NSAP. The leading diagnoses changed after CT in a large proportion of patients with a pre-CT diagnosis of NSAP (38%, 20/52). In regression analysis, we found that physicians' pre-CT diagnostic confidence was inversely associated with a post-CT diagnosis of NSAP in patients with a pre-CT diagnosis other than NSAP (p = 0.0001). No other associations were significant in both primary and sensitivity analyses. CONCLUSION: With the exception of physicians' pre-CT diagnostic confidence, the factors evaluated were not associated with a post-CT diagnosis of NSAP.

Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision Making of Thoracic Surgeons: A 2-year Prospective Study.

Purpose To determine the impact of nonvascular thoracic magnetic resonance (MR) imaging on the clinical decision making and diagnostic certainty of thoracic surgeons. Materials and Methods Seven thoracic surgeons at Massachusetts General Hospital, an academic quaternary referral hospital, participated in this 2-year, prospective, institution review board-approved, HIPAA-compliant pre- and post-MR imaging survey study after completing a one-time demographic survey. Between July 16, 2013, and July 13, 2015, each time a thoracic surgeon ordered a nonvascular thoracic MR imaging study via radiology order entry, he or she was sent a link to the pre-test survey that ascertained the clinical rationale for MR imaging, the clinical management plan if MR imaging was not an option, and pre-test diagnostic certainty. Upon completion of the MR imaging report, the surgeon was sent a link to the post-test survey assessing if/how MR imaging changed clinical management, the surgeon's comfort with the clinical management plan, and post-test diagnostic certainty. Data were analyzed with Student t, Wilcoxon, and McNemar tests. Results A total of 99 pre- and post-test surveys were completed. Most MR imaging studies (64 of 99 [65%]) were requested because of indeterminate computed tomographic findings. The use of MR imaging significantly reduced the number of planned surgical interventions (P < .001), modified the surgical approach in 54% (14 of 26) of surgical cases, and increased surgeon comfort with the patient management plan in 95% (94 of 99) of cases. Increased diagnostic certainty as a result of MR imaging was highly significant (P < .0001). In 21% (21 of 99) of cases, definitive MR imaging results warranted no further follow-up or clinical care. Conclusion In appropriate cases, assessment with nonvascular thoracic MR imaging substantially affects the clinical decision making and diagnostic certainty of thoracic surgeons. (©) RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on May 2, 2016.

Changes in Physician Decision Making after CT: A Prospective Multicenter Study in Primary Care Settings.

Purpose To determine the effect of computed tomography (CT) results on physician decision making in three common clinical scenarios in primary care. Materials and Methods This research was approved by the institutional review board (IRB) and was HIPAA compliant. All physicians consented to participate with an opt-in or opt-out mechanism; patient consent was waived with IRB approval. In this prospective multicenter observational study, outpatients referred by primary care providers (PCPs) for CT evaluation of abdominal pain, hematuria, or weight loss were identified. Prior to CT, PCPs were surveyed to elicit their leading diagnosis, confidence in that diagnosis (confidence range, 0%-100%), a rule-out diagnosis, and a management plan if CT were not available. Surveys were repeated after CT. Study measures were the proportion of patients in whom leading diagnoses and management changed (PCP management vs specialist referral vs emergency department transfer), median changes in diagnostic confidence, and the proportion of patients in whom CT addressed rule-out diagnoses. Regression analyses were used to identify associations between study measures and site and participant characteristics. Specifically, logistic regression analysis was used for binary study measures (change in leading diagnosis, change in management), and linear regression analysis was used for the continuous study measure (change in diagnostic confidence). Accrual began on September 5, 2012, and ended on June 28, 2014. Results In total, 91 PCPs completed pre- and post-CT surveys in 373 patients. In patients with abdominal pain, hematuria, or weight loss, leading diagnoses changed after CT in 53% (131 of 246), 49% (36 of 73), and 57% (27 of 47) of patients, respectively. Management changed in 35% (86 of 248), 27% (20 of 74), and 54% (26 of 48) of patients, respectively. Median absolute changes in diagnostic confidence were substantial and significant (+20%, +20%, and +19%, respectively; P ≤ .001 for all); median confidence after CT was high (90%, 88%, and 80%, respectively). PCPs reported CT was helpful in confirming or excluding rule-out diagnoses in 98% (184 of 187), 97% (59 of 61), and 97% (33 of 34) of patients, respectively. Significant associations between primary measures and site and participant characteristics were not identified. Conclusion Changes in PCP leading diagnoses and management after CT were common, and diagnostic confidence increased substantially. © RSNA, 2016 Online supplemental material is available for this article.

CT in the Emergency Department: A Real-Time Study of Changes in Physician Decision Making.

PURPOSE: To determine how physicians' diagnoses, diagnostic uncertainty, and management decisions are affected by the results of computed tomography (CT) in emergency department settings. MATERIALS AND METHODS: This study was approved by the institutional review board and compliant with HIPAA. Data were collected between July 12, 2012, and January 13, 2014. The requirement to obtain patient consent was waived. In this prospective, four-center study, patients presenting to the emergency department who were referred for CT with abdominal pain, chest pain and/or dyspnea, or headache were identified. Physicians were surveyed before and after CT to determine the leading diagnosis, diagnostic confidence (on a scale of 0% to 100%), alternative "rule out" diagnosis, and management decisions. Primary measures were the proportion of patients for whom the leading diagnosis or admission decision changed and median changes in diagnostic confidence. Secondary measures addressed alternative diagnoses and return-to-care visits (eg, to emergency department) at 1-month follow-up. Regression analysis was used to identify associations between primary measures and site and participant characteristics. RESULTS: Both surveys were completed for 1280 patients by 245 physicians. The leading diagnosis changed in 235 of 460 patients with abdominal pain (51%), 163 of 387 with chest pain and/or dyspnea (42%), and 103 of 433 with headache (24%). Pre-CT diagnostic confidence was inversely associated with the likelihood of a diagnostic change (P < .0001). Median changes in confidence were substantial (increases of 25%, 20%, and 13%, respectively, for patients with abdominal pain, chest pain and/or dyspnea, and headache; P < .0001); median post-CT confidence was high (95% for all three groups). CT helped confirm or exclude at least 95% of alternative diagnoses. Admission decisions changed in 116 of 457 patients with abdominal pain (25%), 72 of 387 with chest pain and/or dyspnea (19%), and 81 of 426 with headache (19%). During follow-up, 70 of 450 patients with abdominal pain (15%), 53 of 387 with chest pain and/or dyspnea (14%), and 49 of 433 with headache (11%) returned for the same indication. In general, changes in leading diagnosis, diagnostic confidence, and admission decisions were not well explained with site or participant characteristics. CONCLUSION: Physicians' diagnoses and admission decisions changed frequently after CT, and diagnostic uncertainty was alleviated.

Occult Histopathology and Its Predictors in Contralateral and Bilateral Prophylactic Mastectomies.

BACKGROUND: The last decade has seen an increasing prevalence of prophylactic mastectomies with decreasing age of patients treated for breast cancer. Data are limited on the prevalence of histopathologic abnormalities in this population. This study aimed to measure the prevalence of histopathologic findings in contralateral prophylactic mastectomy (CPM) and bilateral prophylactic mastectomy (BPM) patients and identify predictors of findings. METHODS: Our institution's prophylactic mastectomies from 2004 to 2011 were reviewed. Breast specimens with prior malignancies were excluded. Patient factors and pathology reports were collected. Independent predictive factors were identified with univariate and multivariate logistic analysis. RESULTS: A total of 524 specimens in 454 patients were identified. Malignancy was found in 7.0% of CPM and 5.7% of BPM specimens. In CPM patients, ipsilateral lobular carcinoma-in situ [odds ratio (OR) 4.0] and mammogram risk group (OR 2.0) were predictive of malignancy. Age group (OR 1.5), ipsilateral lobular carcinoma-in situ (OR 2.3), and prior bilateral salpingo-oophorectomy (OR 0.3) were predictive of moderate- to high-risk histopathology. Only increasing age group was predictive of increased moderate- to high-risk histopathology in BPM patients (OR 2.3). There were no independent predictors of malignancy in BPM. BRCA status was not predictive in either CPM or BPM. CONCLUSIONS: Patients with lobular carcinoma-in situ in the index breast or high-risk mammograms have a higher prevalence of malignancies. Although BRCA patients may benefit from prophylactic mastectomy, the genetic diagnosis does not increase the prevalence of detecting occult pathology. BPM patients can be counseled about relative risk, where occult pathology increases with age.

Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas.

OBJECTIVES: To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. METHODS: Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. RESULTS: There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. CONCLUSION: Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. KEY POINTS: • CT-attenuation of adipose tissue and muscle predict mortality in sarcoma patients • CT-attenuation predicts mortality independent of established prognostic factors • Patients with sarcomas often undergo CT for staging or surveillance • Adipose tissue and muscle attenuation could serve as biomarkers for mortality.

Left Ventricular Global Longitudinal Strain in HER-2 + Breast Cancer Patients Treated with Anthracyclines and Trastuzumab Who Develop Cardiotoxicity Is Associated with Subsequent Recovery of Left Ventricular Ejection Fraction.

AIM: The combination of anthracyclines (AC) and trastuzumab (TRZ) is highly effective in patients with aggressive HER-2 + breast cancer, but has a significant risk of cardiotoxicity (CT). Trastuzumab-induced CT may be reversible. The aim of this study was to identify echocardiographic parameters associated with recovery of left ventricular ejection fraction (LVEF) in patients who developed CT after AC and TRZ treatment. METHODS AND RESULTS: Women with newly diagnosed breast cancer treated with AC followed by TRZ and monitored with serial echocardiograms were retrospectively studied. Left ventricular end-diastolic and systolic volumes, LVEF, and global longitudinal strain (GLS) were examined. Development and reversibility of CT were defined based on changes in LVEF according to the 2014 ASE/EACVI recommendations. Cox analysis was used to determine the association of echocardiographic variables with the subsequent development and reversibility of CT. Ninety-five patients underwent 5 echocardiograms or more in a 17-month (13-28 months) follow-up period. Nineteen patients (20%) developed CT. Left ventricular volumes, LVEF, and GLS measured after AC completion identified the subsequent development of CT. Of the 19 patients with CT, the LVEF partially or fully recovered in 13 (68%). GLS at the time of CT diagnosis was associated with subsequent recovery of LVEF (P = 0.004). CONCLUSION: In patients with breast cancer treated with AC and TRZ who develop CT, GLS at the time of CT diagnosis is associated with subsequent recovery of LVEF and may be useful for risk stratification and to guide treatment.

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane.

PURPOSE: To evaluate the diagnostic accuracy of shear-wave elastography (SWE) for the diagnosis of malignancy in follicular lesions and to identify the optimal SWE measurement plane. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant, single-institution, prospective pilot study. Subjects scheduled for surgery after a previous fine-needle aspiration report of "atypia of undetermined significance" or "follicular lesion of undetermined significance," "suspicion for follicular neoplasm," or "suspicion for Hurthle cell neoplasm," were enrolled after obtaining informed consent. Subjects underwent conventional ultrasonography (US), Doppler evaluation, and SWE preoperatively, and their predictive value for thyroid malignancy was evaluated relative to the reference standard of surgical pathologic findings. RESULTS: Thirty-five patients (12 men, 23 women) with a mean age of 55 years (range, 23-85 years) and a fine-needle aspiration diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (n = 16), suspicion for follicular neoplasm (n = 14), and suspicion for Hurthle cell neoplasm (n = 5) were enrolled in the study. Male sex was a statistically significant (P = .02) predictor of malignancy, but age was not. No sonographic morphologic parameter, including nodule size, microcalcification, macrocalcification, halo sign, taller than wide dimension, or hypoechogenicity, was associated with malignancy. Similarly, no Doppler feature, including intranodular vascularity, pulsatility index, resistive index, or peak-systolic velocity, was associated with malignancy. Higher median SWE tissue Young modulus estimates from the transverse insonation plane were associated with malignancy, yielding an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.62, 1.00) for differentiation of malignant from benign nodules. At a cutoff value of 22.3 kPa, sensitivity, specificity, positive predictive value, and negative predictive value of 82%, 88%, 75%, and 91%, respectively, were observed. CONCLUSION: This prospective pilot study indicates that SWE may be a valuable tool in preoperative malignancy risk assessment of follicular-patterned thyroid nodules.

Shear-wave elastography for the estimation of liver fibrosis in chronic liver disease: determining accuracy and ideal site for measurement.

PURPOSE: To evaluate the accuracy of shear-wave elastography (SWE) for staging liver fibrosis in patients with diffuse liver disease (including patients with hepatitis C virus [HCV]) and to determine the relative accuracy of SWE measurements obtained from different hepatic acquisition sites for staging liver fibrosis. MATERIALS AND METHODS: The institutional review board approved this single-institution prospective study, which was performed between January 2010 and March 2013 in 136 consecutive patients who underwent SWE before their scheduled liver biopsy (age range, 18-76 years; mean age, 49 years; 70 men, 66 women). Informed consent was obtained from all patients. SWE measurements were obtained at four sites in the liver. Biopsy specimens were reviewed in a blinded manner by a pathologist using METAVIR criteria. SWE measurements and biopsy results were compared by using the Spearman correlation and receiver operating characteristic (ROC) curve analysis. RESULTS: SWE values obtained at the upper right lobe showed the highest correlation with estimation of fibrosis (r = 0.41, P < .001). Inflammation and steatosis did not show any correlation with SWE values except for values from the left lobe, which showed correlation with steatosis (r = 0.24, P = .004). The area under the ROC curve (AUC) in the differentiation of stage F2 fibrosis or greater, stage F3 fibrosis or greater, and stage F4 fibrosis was 0.77 (95% confidence interval [CI]: 0.68, 0.86), 0.82 (95% CI: 0.75, 0.91), and 0.82 (95% CI: 0.70, 0.95), respectively, for all subjects who underwent liver biopsy. The corresponding AUCs for the subset of patients with HCV were 0.80 (95% CI: 0.67, 0.92), 0.82 (95% CI: 0.70, 0.95), and 0.89 (95% CI: 0.73, 1.00). The adjusted AUCs for differentiating stage F2 or greater fibrosis in patients with chronic liver disease and those with HCV were 0.84 and 0.87, respectively. CONCLUSION: SWE estimates of liver stiffness obtained from the right upper lobe showed the best correlation with liver fibrosis severity and can potentially be used as a noninvasive test to differentiate intermediate degrees of liver fibrosis in patients with liver disease.

Diagnostic yield of recommendations for chest CT examination prompted by outpatient chest radiographic findings.

PURPOSE: To evaluate the diagnostic yield of recommended chest computed tomography (CT) prompted by abnormalities detected on outpatient chest radiographic images. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval; informed consent was waived. Reports of all outpatient chest radiographic examinations performed at a large academic center during 2008 (n = 29 138) were queried to identify studies that included a recommendation for a chest CT imaging. The radiology information system was queried for these patients to determine if a chest CT examination was obtained within 1 year of the index radiographic examination that contained the recommendation. For chest CT examinations obtained within 1 year of the index chest radiographic examination and that met inclusion criteria, chest CT images were reviewed to determine if there was an abnormality that corresponded to the chest radiographic finding that prompted the recommendation. All corresponding abnormalities were categorized as clinically relevant or not clinically relevant, based on whether further work-up or treatment was warranted. Groups were compared by using t test and Fisher exact test with a Bonferroni correction applied for multiple comparisons. RESULTS: There were 4.5% (1316 of 29138 [95% confidence interval {CI}: 4.3%, 4.8%]) of outpatient chest radiographic examinations that contained a recommendation for chest CT examination, and increasing patient age (P < .001) and positive smoking history (P = .001) were associated with increased likelihood of a recommendation for chest CT examination. Of patients within this subset who met inclusion criteria, 65.4% (691 of 1057 [95% CI: 62.4%, 68.2%) underwent a chest CT examination within the year after the index chest radiographic examination. Clinically relevant corresponding abnormalities were present on chest CT images in 41.4% (286 of 691 [95% CI: 37.7%, 45.2%]) of cases, nonclinically relevant corresponding abnormalities in 20.6% (142 of 691 [95% CI: 17.6%, 23.8%]) of cases, and no corresponding abnormalities in 38.1% (263 of 691 [95% CI: 34.4%, 41.8%]) of cases. Newly diagnosed, biopsy-proven malignancies were detected in 8.1% (56 of 691 [95% CI: 6.2%, 10.4%]) of cases. CONCLUSION: A radiologist recommendation for chest CT to evaluate an abnormal finding on an outpatient chest radiographic examination has a high yield of clinically relevant findings.

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab.

BACKGROUND: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS: Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

Prospective analysis of an interprofessional team training program using high-fidelity simulation of contrast reactions.

OBJECTIVE: Successful management of a contrast reaction requires prompt recognition and treatment and effective team dynamics among radiologists, technologists, and nurses. A radiology department implemented a simulation program in which teams of nurses, technologists, and physicians managed simulated contrast reactions. The purpose of this study was to evaluate whether simulation improved the participants' abilities to manage a contrast reaction and work in a team during an emergency. SUBJECTS AND METHODS: Physicians, nurses, and technologists worked in inter-professional teams to manage two high-fidelity simulated adverse contrast reactions. Participants completed surveys before and after the simulation that included knowledge-based questions about the appropriate management of contrast reactions. Surveys also included questions for assessing participants' perceptions of their ability to manage adverse contrast reactions, measured with a 6-point Likert scale. Before and after comparisons were made with the McNemar test with a Bonferroni correction requiring p ≤ 0.003 for significance. For the other analyses, p ≤ 0.05 was considered significant. RESULTS: After completion of the simulation exercises, participants had significant improvement in knowledge (p < 0.001). After the simulation, participants reported significant improvement in their ability to manage an anaphylactoid reaction and their ability to work in a team (p < 0.00001). Participants requested repeat simulation exercises every 6-12 months. CONCLUSION: Simulation exercises improved the self-reported ability of radiology personnel to manage contrast reactions and work in a team during an emergency. Simulation should be incorporated into future educational initiatives to improve patient safety in radiology practices.

Statistics 101 for Radiologists.

Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced.

Percutaneous CT-guided needle biopsies of musculoskeletal tumors: a 5-year analysis of non-diagnostic biopsies.

OBJECTIVE: To study non-diagnostic CT-guided musculoskeletal biopsies and take steps to minimize them. Specifically we asked: (1) What malignant diagnoses have a higher non-diagnostic rate? (2) What factors of a non-diagnostic biopsy may warrant more aggressive pursuit? (3) Do intra-procedural frozen pathology (FP) or point-of-care (POC) cytology reduce the non-diagnostic biopsy rate? MATERIALS AND METHODS: This study was IRB-approved and HIPAA-compliant. We retrospectively reviewed 963 consecutive CT-guided musculoskeletal biopsies. We categorized pathology results as malignant, benign, or non-diagnostic and recorded use of FP or POC cytology. Initial biopsy indication, final diagnosis, method of obtaining the final diagnosis of non-diagnostic biopsies, age of the patient, and years of biopsy attending experience were recorded. Groups were compared using Pearson's χ(2) test or Fisher's exact test. RESULTS: In all, 140 of 963 (15%) biopsies were non-diagnostic. Lymphoma resulted in more non-diagnostic biopsies (P < 0.0001). While 67% of non-diagnostic biopsies yielded benign diagnoses, 33% yielded malignant diagnoses. Patients whose percutaneous biopsy was indicated due to the clinical context without malignancy history almost always generated benign results (96%). Whereas 56% of biopsies whose indication was an imaging finding of a treatable lesion were malignant, 20% of biopsies whose indication was a history of malignancy were malignant. There was no statistically significant difference in the nondiagnostic biopsy rates of pediatric versus adult patients (P = 0.8) and of biopsy attendings with fewer versus more years of experience (P = 0.5). The non-diagnostic rates of biopsies with FP (8%), POC cytology (25%), or neither (24%) were significantly different (P < 0.0001). CONCLUSION: Lymphoma is the malignant diagnosis most likely to result in a non-diagnostic biopsy. If the clinical and radiologic suspicion for malignancy is high, repeat biopsy is warranted. If the clinical context suggests a benign lesion, a non-diagnostic biopsy may be considered reassuring. Frozen pathology may decrease the non-diagnostic biopsy rate.

Behind the numbers: inverse probability weighting.

Inverse probability weighting is a propensity score-based technique that can be used to compensate for imbalance in study groups. It is an alternative to regression-based adjustment of the outcomes. It has advantages over matching of cases on the basis of propensity scores when there are more than two groups to compare, when finding matches results in insufficient sample sizes, or when the data are censored. However, it can create artificial imbalance unless it is applied carefully. In this article, an introduction to inverse probability weighting is provided by using the Yang et al study published in this issue of Radiology as an example.

Discriminating parathyroid adenoma from local mimics by using inherent tissue attenuation and vascular information obtained with four-dimensional CT: formulation of a multinomial logistic regression model.

PURPOSE: To identify a set of parameters, which are based on tissue enhancement and native iodine content obtained from a standardized triple-phase four-dimensional (4D) computed tomographic (CT) scan, that define a multinomial logistic regression model that discriminates between parathyroid adenoma (PTA) and thyroid nodules or lymph nodes. MATERIALS AND METHODS: Informed consent was waived by the institutional review board for this retrospective HIPAA-compliant study. Electronic medical records were reviewed for 102 patients with hyperparathyroidism who underwent triple-phase 4D CT and parathyroid surgery resulting in pathologically proved removal of adenoma from July 2010 through December 2011. Hounsfield units were measured in PTA, thyroid, lymph nodes, and aorta and were used to determine seven parameters characterizing tissue contrast enhancement. These were used as covariates in 10 multinomial logistic regression models. Three models with one covariate, four models with two covariates, and three models with three covariates were investigated. Receiver operating characteristic (ROC) analysis was performed to determine how well each model discriminated between adenoma and nonadenomatous tissues. Statistical differences between the areas under the ROC curves (AUCs) for each model pair were calculated, as well as sensitivity, specificity, accuracy, negative predictive value, and positive predictive value. RESULTS: A total of 120 lesions were found; 112 (93.3%) lesions were weighed, and mean and median weights were 589 and 335 mg, respectively. The three-covariate models were significantly identical (P > .65), with largest AUC of 0.9913 ± 0.0037 (standard error), accuracy of 96.9%, and sensitivity, specificity, negative predictive value, and positive predictive value of 94.3%, 98.3%, 97.1%, and 96.7%, respectively. The one- and two-covariate models were significantly less accurate (P < .043). CONCLUSION: A three-covariate multinomial logistic model derived from a triple-phase 4D CT scan can accurately provide the probability that tissue is PTA and performs significantly better than models using one or two covariates.