Frailty Screening in the Emergency Department: Comparing the Variable Indicative of Placement Risk, Clinical Frailty Scale and PRISMA-7.

Prompt recognition of frailty in the emergency department (ED) is important to identify patients at higher risk of adverse outcomes. Despite this, few studies examine the diagnostic accuracy of screening instruments for frailty, instead focusing on predictive validity. We compared three commonly used, short frailty screens to an independent comprehensive geriatric assessment (CGA) in an urban University Hospital ED. Consecutive attendees aged ≥70 years were screened by trained raters, blind to the CGA, with the Variable Indicative of Placement risk (VIP), 3 and 4-item versions, Clinical Frailty Scale (CFS) and PRISMA-7. Accuracy was measured from the area under the ROC curve (AUROC). In total, 197 patients were included, median age 79 (±10); 46% were female. Half (49%) were confirmed as frail after CGA. All instruments differentiated frail from non-frail states, although the CFS (AUROC: 0.91) and PRISMA-7 (AUROC: 0.90) had higher accuracy compared to the VIP-4 (AUROC: 0.84) and VIP-3 (AUROC: 0.84). The CFS was significantly more accurate than the VIP-3 (p = 0.026) or VIP-4 (p = 0.047). There was no significant difference between the CFS and PRISMA-7 (p = 0.90). The CFS and PRISMA-7 were more accurate and should be considered in preference to the VIP (3 or 4-item versions) to identify frailty in EDs.

False-Negative Rates of Breast Cancer Screening with and without Digital Breast Tomosynthesis.

Background Screening with digital breast tomosynthesis (DBT) improves breast cancer detection and recall rates compared with those obtained with digital mammography (DM); however, the impact of DBT on patient survival has not been established. False-negative (FN) screening examinations can be a surrogate for long-term outcomes, such as breast cancer morbidity and mortality. Purpose To determine if screening with DBT is associated with lower FN rates, detection of cancers with more favorable prognoses, and improved performance outcomes versus DM. Materials and Methods This retrospective study involved 10 academic and community practices. DM screening examinations 1 year prior to DBT implementation and DBT screening examinations from the start date until June 30, 2013, were linked to cancers through June 30, 2014, with data collection in 2016 and analysis in 2018-2019. Cancers after FN examinations were characterized by presentation, either symptomatic or asymptomatic. FN rates, sensitivity, specificity, cancer detection and recall rates, positive predictive values, tumor size, histologic features, and receptor profile were compared. Results A total of 380 641 screening examinations were included. There were 183 989 DBT and 196 652 DM examinations. With DBT, rates trended lower for overall FN examinations (DBT, 0.6 per 1000 screens; DM, 0.7 per 1000 screens; P = .20) and symptomatic FN examinations (DBT, 0.4 per 1000 screens; DM, 0.5 per 1000 screens; P = .21). Asymptomatic FN rates trended higher in women with dense breasts (DBT, 0.14 per 1000 screens; DM: 0.07 per 1000 screens; P = .07). With DBT, improved sensitivity (DBT, 89.8% [966 of 1076 cancers]; DM, 85.6% [789 of 922 cancers]; P = .004) and specificity (DBT, 90.7% [165 830 of 182 913 examinations]; DM, 89.1% [174 480 of 195 730 examinations]; P < .001) were observed. Overall, cancers identified with DBT were more frequently invasive (P < .001), had fewer positive lymph nodes (P = .04) and distant metastases (P = .01), and had lower odds of an FN finding of advanced cancer (odds ratio, 0.9 [95% CI: 0.5, 1.5]). Conclusion Screening with digital breast tomosynthesis improves sensitivity and specificity and reveals more invasive cancers with fewer nodal or distant metastases. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schattner in this issue.

Retraction Note to: The American Society of Breast Surgeons 2017 Annual Meeting Official Proceedings, Volume XVIII.

The Editors of Annals of Surgical Oncology have retracted the following poster session abstract following an investigation by the authors' institution, which found that the study was not submitted to the IRB for approval.

New Breast Cancer Radiotherapy Technology Confers Higher Complications and Costs Before Effectiveness Proven: A Medicare Data Analysis.

A new breast cancer treatment, brachytherapy-based accelerated partial breast radiotherapy (RT), was adopted before long-term effectiveness evidence, potentially increasing morbidity and costs compared with whole breast RT. The aim of this study was to estimate complication rates and RT-specific and 1-year costs for a cohort of female Medicare beneficiaries diagnosed with breast cancer (N = 47 969). We analyzed 2005-2007 Medicare claims using multivariable logistic regression for complications and generalized linear models (log link, gamma distribution) for costs. Overall, 11% (n = 5296) underwent brachytherapy-based RT; 9.4% had complications. Odds of any complication were higher (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.49-1.76) for brachytherapy versus whole breast RT, similarly to seroma (OR: 2.85; 95% CI: 1.97-4.13), wound complication/infection (OR: 1.72; 95% CI: 1.52-1.95), cellulitis (OR: 1.48; 95% CI: 1.27-1.73), and necrosis (OR: 2.07; 95% CI: 1.55-2.75). Mean RT-specific and 1-year total costs for whole breast RT were $6375, and $19 917, $4886, and $4803 lower than brachytherapy ( P < .0001). Multivariable analyses indicated brachytherapy yielded 76% higher RT costs (risk ratio: 1.76; 95% CI: 1.74-1.78, P < .0001) compared with whole breast RT. Brachytherapy had higher complications and costs before long-term evidence proved its effectiveness. Policies should require treatment registries with reimbursement incentives to capture surveillance data for new technologies.

Effect of age on breast cancer screening using tomosynthesis in combination with digital mammography.

PURPOSE: To determine the effect of tomosynthesis imaging as a function of age for breast cancer screening. METHODS: Screening performance metrics from 13 institutions were examined for 12 months prior to introduction of tomosynthesis (period 1) and compared to those after introduction of tomosynthesis (period 2, range 3-22 months). Screening metrics for women ages 40-49, 50-59, 60-69, and 70+ , included rates per 1000 screens for recalls, biopsies, cancers, and invasive cancers detected. RESULTS: Performance parameters were compared for women screened with digital mammography alone (n = 278,908) and digital mammography + tomosynthesis (n = 173,414). Addition of tomosynthesis to digital mammography produced significant reductions in recall rates for all age groups and significant increases in cancer detection rates for women 40-69. Largest recall rate reduction with tomosynthesis was for women 40-49, decreasing from 137 (95% CI 117-156) to 115 (95% CI 95-135); difference, -22 (95% CI -26 to -18; P < .001). Simultaneous increase in invasive cancer detection rate for women 40-49 from 1.6 (95% CI 1.2-1.9) to 2.7 (95% CI 2.2-3.1) with tomosynthesis (difference, 1.1; 95% CI 0.6-1.6; P < .001) was observed. CONCLUSIONS: Addition of tomosynthesis to digital mammography increased invasive cancer detection rates for women 40-69 and decreased recall rates for all age groups with largest performance gains seen in women 40-49. The similar performance seen with tomosynthesis screening for women in their 40s compared to digital mammography for women in their 50s argues strongly for commencement of mammography screening at age 40 using tomosynthesis.

Update on Preoperative Breast Localization.

The radiologist plays an important role in detection, diagnosis, localization, pathologic correlation, and follow-up imaging of breast cancer. A successful breast surgical treatment program relies on the image guidance tools and skills of the radiologist and surgeon. This article reviews the evolving tools available for preoperative localization. Non-wire devices provide a safe, efficient, noninferior alternative to wire localization and can be placed 0 to 30 days before scheduled surgery. This technology may evolve to other longer-term, efficient, and cost-effective applications for patients who require neoadjuvant treatment or who have findings visible only at MR imaging.

ACR Appropriateness Criteria Breast Cancer Screening.

Mammography is the recommended method for breast cancer screening of women in the general population. However, mammography alone does not perform as well as mammography plus supplemental screening in high-risk women. Therefore, supplemental screening with MRI or ultrasound is recommended in selected high-risk populations. Screening breast MRI is recommended in women at high risk for breast cancer on the basis of family history or genetic predisposition. Ultrasound is an option for those high-risk women who cannot undergo MRI. Recent literature also supports the use of breast MRI in some women of intermediate risk, and ultrasound may be an option for intermediate-risk women with dense breasts. There is insufficient evidence to support the use of other imaging modalities, such as thermography, breast-specific gamma imaging, positron emission mammography, and optical imaging, for breast cancer screening. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Stage I Breast Cancer: Initial Workup and Surveillance for Local Recurrence and Distant Metastases in Asymptomatic Women.

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® Stage I Breast Carcinoma.

Stage I breast carcinoma is classified when an invasive breast carcinoma is ≤2 cm in diameter (T1), with no regional (axillary) lymph node metastases (N0) and no distant metastases (M0). The most common sites for metastases from breast cancer are the skeleton, lung, liver, and brain. In general, women and health care professionals prefer intensive screening and surveillance after a diagnosis of breast cancer. Screening protocols include conventional imaging such as chest radiography, bone scan, ultrasound of the liver, and MRI of brain. It is uncertain whether PET/CT will serve as a replacement for current imaging technologies. However, there are no survival or quality-of-life differences for women who undergo intensive screening and surveillance after a diagnosis of stage I breast carcinoma compared with those who do not. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria Palpable Breast Masses.

A palpable breast mass is one of the most common presenting features of breast carcinoma. However, the clinical features are frequently nonspecific. Imaging performed before biopsy is helpful in characterizing the nature of the mass. For women with clinically detected breast masses, the vast majority will require evaluation with ultrasound. Diagnostic mammography is the initial imaging modality of choice for women aged ≥ 40 years; ultrasound is typically necessary unless a definitively benign mass is identified as the etiology of the clinical finding. For evaluating women aged <30 years and women who are pregnant or lactating, ultrasound is used for initial evaluation. For women aged 30 to 39 years, either ultrasound or diagnostic mammography may be used for initial evaluation. MRI is rarely indicated to evaluate a clinically detected finding. Biopsy is indicated for masses with suspicious features. Short-term follow-up is a reasonable alternative to biopsy for solid masses with probably benign features suggesting fibroadenoma. Correlation between imaging and the clinical finding is essential. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Disease-free survival according to the use of postmastectomy radiation therapy after neoadjuvant chemotherapy.

INTRODUCTION: The purpose of the study was to determine predictors of recurrence for patients treated with neoadjuvant chemotherapy (NAC) and mastectomy according to the use of postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS: An analysis of 161 clinically staged T1 to T3/N0 to N3 patients treated with NAC and mastectomy with and without PMRT at our institution from 2003 to 2010 was conducted. The Kaplan-Meier product limit method was used to estimate survival and time to recurrence rates and the log-rank test was used to compare groups. A Cox proportional hazard regression analysis was carried out for time to recurrence, radiation therapy, and their interaction in the model. RESULTS: The median follow-up period was 48 months and 18 patients developed a recurrence. The 5-year recurrence rate and overall survival was 16.1% (95% confidence interval [CI], 9.6%-26.3%) and 93.6% (95% CI, 88.2%-97.0%), respectively. Patients who underwent PMRT had a decreased risk of recurrence compared with patients who did not (hazard ratio [HR], 0.25; 95% CI, 0.097-0.661; P < .005). The 5-year disease-free survival (DFS) rate for those who received PMRT was 91.3% (95% CI, 82.8%-95.7%) and 64.8% (95% CI, 37.8%-82.4%) for those who did not (P = .0126). Among all clinicopathologic factors examined, pathologic T stage (ypT) and pathological N stage (ypN) significantly correlated with the risk of recurrence (P < .05). Patients with any pathological nodal disease had an increased risk of recurrence compared with patients who were pathologically node-negative (HR, 7.196; 95% CI, 2.05-25.264; P < .002). CONCLUSION: Patients treated with NAC and mastectomy, but without PMRT had a higher risk recurrence with increasing ypT and ypN stages. PMRT might increase DFS.

Identification and expression of GnRH2 and GnRH3 in the black sea bass (Centropristis striata), a hermaphroditic teleost.

We cloned two cDNAs for two gonadotropin-releasing hormones, GnRH2 (chicken GnRH-II) and GnRH3 (salmon GnRH), respectively, from the black sea bass (Centropristis striata). Black sea bass are protogynous hermaphroditic teleosts that change from females to males between 2 and 5 years of age. Similar to other GnRH precursors, the precursors of black sea bass GnRH2 and GnRH23 consisted of a signal peptide, decapeptide, a downstream processing site, and a GnRH-associated peptide. Our analyses failed to identify GnRH1. GnRH3 precursor transcript was more widely distributed in a variety of tissues compared with GnRH2. Further examination of GnRH expression and gonadal histology was done in black sea bass from three different size groups: small (11.4-44.1 g), medium (179.4-352.2 g) and large (393.8-607.3 g). Interestingly, GnRH3 expression occurred only in the pituitaries of males in the small and medium groups compared with expression of GnRH2. Future functional studies of the sea bass GnRHs will be valuable in elucidating the potential underlying neuroendocrine mechanisms of black sea bass reproduction and may ultimately contribute to management advances in this commercially important fish.

ACR Appropriateness Criteria stage I breast cancer: initial workup and surveillance for local recurrence and distant metastases in asymptomatic women.

Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Lessons from the leucovorin shortages between 2009 and 2012 in a medicare advantage population: where do we go from here?

BACKGROUND: Three distinct shortages of the generic drug leucovorin, a reduced form of folic acid used in several chemotherapy regimens, were reported by the US Food and Drug Administration (FDA) between 2008 and 2014. Levoleucovorin, an alternative therapy to leucovorin, failed to demonstrate superiority over leucovorin in clinical trials and is substantially more expensive. OBJECTIVE: To calculate the impact of the leucovorin shortages on primary treatment costs to patients and a health plan, and to present strategies for health plans to deal with future drug shortages. METHODS: This retrospective descriptive study was conducted using Humana's Medicare Advantage prescription drug plan administrative claims database between January 1, 2009, and December 31, 2012. A total of 1542 patients with at least 1 medical or pharmacy claim for either leucovorin or levoleucovorin during the first 3 months of the respective plan year (between 2009 and 2012) who had continuous enrollment for the entirety of the same plan year, were included in this study. Trends in primary treatment costs-defined as the drug cost of leucovorin or levoleucovorin-over the 4-year evaluation period were assessed. The mean annual patient out-of-pocket (OOP) costs and the mean plan-paid per member per month (PMPM) costs were also calculated. RESULTS: The percentage of patients receiving leucovorin decreased annually, with a 15.8% drop from 2010 to 2011. This reduction was accompanied by a 6.6% increase in patients receiving levoleucovorin. The mean annual patient OOP costs were $167 to $714 higher for levoleucovorin than for leucovorin. Similarly, the mean plan-paid PMPM costs were higher (up to $1667 PMPM) for levoleucovorin than for leucovorin. The aggregate costs for the 2 drugs increased steadily, including the patient OOP costs and the plan-paid PMPM costs. The most prominent cost increase occurred between 2010 and 2011, with a 3.8-fold increase in patient OOP costs and a 5-fold increase in the plan-paid PMPM costs. This corresponded to the timing of the second leucovorin shortage announcement by the FDA in June 2010. CONCLUSIONS: Health plans can play an important role in minimizing the impact of drug shortages by identifying the affected patient population, identifying therapeutic alternatives, assisting providers with alternative sourcing strategies when possible, adjusting approval processes, and implementing quality management or pathway programs.

Diffusion of accelerated partial breast radiotherapy in the United States: physician-level and patient-level analyses.

PURPOSE: To evaluate diffusion of brachytherapy-based accelerated partial breast radiotherapy (RT) in the United States, a new breast cancer treatment requiring 5 days twice daily, rather than daily treatment for 6-7 weeks. It has limited long-term effectiveness data compared with standard whole breast RT. DATA AND METHODS: We used 2005-2008 Medicare claims for female Medicare beneficiaries receiving RT after breast-conserving surgery merged with physician and area-based data (n=74,254 patient-subjects; n=1901 physicians), applying logistic regression to estimate: (1) proportion of patients for whom the radiation oncologist used brachytherapy-based accelerated RT, and (2) probability a patient received brachytherapy-based accelerated RT, clustering on physician. RESULTS: Use of accelerated partial breast RT increased over time (8% in 2005 to 17% in 2008). Physician-level analysis indicates rural physicians were less likely to perform accelerated RT [odds ratio (OR): 0.35-0.49; P<0.002)]; as were those licensed 20+years [OR: 0.54; 95% confidence interval (CI), 0.39-0.74]. Overall, 11.7% of patients received accelerated RT. Treatment post 2005 was associated with increasing odds of receiving accelerated RT (P<0.0001). Older age was associated with lower odds of receiving accelerated RT (reference, 66-69 years old, OR: 0.90, P<0.006), as was black (OR: 0.73;95% CI, 0.63-0.85) or other race (OR: 0.80; 95% CI, 0.65-1.00), living in rural areas (OR: 0.8; P<0.0001), or seeing an older physician [20+years postgraduation (OR: 0.7; 95% CI, 0.5-0.9)]. Patients living in counties with more hospitals with advanced RT facilities were more likely to undergo accelerated RT (OR: 1.4; 95% CI, 1.1-1.8). DISCUSSION: This new technology appears to be in the early phase of diffusion across the United States and is more rapidly being taken up in younger, white patients living in urban and suburban areas with availability of advanced RT facilities. Rural and older patient populations are not tending to undergo the treatment.