A tool to predict disparities in the timeliness of surgical treatment for breast cancer patients in the USA.

PURPOSE: Breast cancer outcomes are impaired by both delays and disparities in treatment. This study was performed to assess their relationship and to provide a tool to predict patient socioeconomic factors associated with risk for delay. METHODS: The National Cancer Database was reviewed between 2004 and 2017 for patients with non-metastatic breast cancer managed with upfront surgery. Times to treatment were measured from the date of diagnosis. Patient, tumor, and treatment factors were assessed with attention paid to sociodemographic variables. RESULTS: 514,187 patients remained after exclusions, with 84.3% White, 10.8% Black, 3.7% Asian, and Hispanics comprising 5.6% of the cohort. Medicaid and uninsured patients had longer mean adjusted time to surgery (≥ 46 days) versus private (36.7 days), Medicare (35.9 days), or other governmental insurance (39.8 days). After adjustment, Black race and Hispanic ethnicity were most impactful, adding 6.0 and 6.4 preoperative days, 10.9 and 11.5 days to chemotherapy, 11.1 and 9.1 days to radiation, and 12.5 and 8.9 days to endocrine therapy, respectively. Income, education, and insurance, among other factors, also affected delay. A nomogram, including race and sociodemographic factors, was created to predict the risk of preoperative delay. CONCLUSION:  Significant disparities exist in timeliness of care for factors, including but not limited to, race and ethnicity. Although exact causes cannot be discerned, these data indicate population subsets whose intervals of care risk being longer than those specified by national quality standards. The nomogram created here may help direct resources to those at highest risk of incurring a treatment delay.

Treatment times in breast cancer patients receiving neoadjuvant vs adjuvant chemotherapy: Is efficiency a benefit of preoperative chemotherapy?

BACKGROUND/OBJECTIVE: Delays in times to surgery, chemotherapy, and radiotherapy impair survival in breast cancer patients. Neoadjuvant chemotherapy (NAC) confers equivalent survival to adjuvant chemotherapy (AC), but it remains unknown which approach facilitates faster initiation and completion of treatment. METHODS: Women ≥18 years old with nonrecurrent, noninflammatory, clinical stage I-III breast cancer diagnosed between 2004 and 2015 who underwent both surgery and chemotherapy were reviewed from the National Cancer Database. RESULTS: Among 155 606 women overall, 28 241 patients received NAC and 127 365 patients received AC. NAC patients had higher clinical T and N stages (35.8% T3/4 vs 4.9% T3/4; 14.4% N2/3 vs 3.7% N2/3). After adjusting for stage and other factors, NAC patients had longer times to begin treatment (36.1 vs 35.4 days adjusted, P = .15), and took significantly longer to start radiotherapy (240.8 vs 218.2 days adjusted, P < .0001), and endocrine therapy (301.6 vs 275.7 days adjusted, P < .0001). Unplanned readmissions (1.2% vs 1.7%), 30-day mortality (0.04% vs 0.01%), and 90-day mortality (0.30% vs 0.08%) were all low and clinically insignificant between NAC and AC. CONCLUSION: Compared to patients receiving AC, those receiving NAC do not start treatment sooner. In addition, patients receiving NAC do not complete treatment faster. Although there are clear indications for administering NAC vs AC, rapidity of treatment should not be considered a benefit of giving chemotherapy preoperatively.

Treatment delays from transfers of care and their impact on breast cancer quality measures.

PURPOSE: Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions. METHODS: Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers ("reporting facilities") in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery. RESULTS: Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p's < 0.0001). On multivariable analysis, the odds of surgery occurring > 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs > 1.73, p's < 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p < 0.0001). CONCLUSIONS: TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

National Accreditation Program for Breast Centers Demonstrates Improved Compliance with Post-Mastectomy Radiation Therapy Quality Measure.

BACKGROUND: The National Accreditation Program for Breast Centers (NAPBC) was established in 2008 by the American College of Surgeons as a quality-improvement program for patients with breast disease. An NAPBC quality measure states post-mastectomy patients with ≥4 positive lymph nodes should receive lymph node radiation therapy (PMRT). Our objective was to examine how NAPBC accreditation has affected compliance with this quality measure. STUDY DESIGN: Women who underwent mastectomy at either an NAPBC-accredited center or a Commission on Cancer-only accredited hospital were identified (2006 to 2013) in the National Cancer Data Base. The NAPBC centers accredited from 2009 to 2011 were included in the analysis. Patients were nested within centers using a mixed effects model to identify PMRT rates at each center before and after accreditation, adjusting for patient and tumor characteristics. RESULTS: Of 34,752 patients from 477 NAPBC-accredited centers and 958 Commission on Cancer-only accredited hospitals who underwent mastectomy with ≥4 positive lymph nodes, 21,638 patients received PMRT during the study period (62.3%). The NAPBC centers yielded a significantly higher rate of PMRT than Commission on Cancer hospitals (66.0% vs 59.2%; p < 0.001). For each year of accreditation (2009 to 2011), centers had significantly higher rates of radiation in the accreditation year compared with the year before accreditation (p < 0.001). Within those centers, the rate of radiation increased post-accreditation in each accreditation year (2009: 62.1% to 71.9%; 2010: 65.5% to 73.2%; 2011: 67.5% to 70.4%). CONCLUSIONS: The NAPBC accreditation is associated with higher PMRT rates and better adherence to the PMRT quality measure. Future studies with more centers and longer follow-up are needed to determine whether this trend continues.

Trends and variation in the use of nipple-sparing mastectomy for breast cancer in the United States.

PURPOSE: For many women, nipple-sparing mastectomy (NSM) provides aesthetic and quality-of-life outcomes superior to skin-sparing mastectomy. Accumulating data suggest that NSM provides similar oncologic outcomes in select breast cancer patients. This study sought to determine national trends in NSM use. METHODS: Using the National Cancer Data Base, 6254 women with breast cancer who underwent NSM between 2010 and 2013 were identified. NSM rates were determined relative to the number of patients who received a mastectomy with reconstruction (n = 114,849). Associations between patient, tumor, and facility characteristics and NSM were assessed using logistic regression. RESULTS: The rate of NSM increased from 2.9 to 8.0 % between 2010 and 2013. NSM was most commonly performed in academic (adjusted odds ratio [OR] 1.43, p < 0.001) and high-volume (OR 1.59, p < 0.001) breast centers. There was up to a 5.8-fold variation in its delivery between geographic census regions (p < 0.001). Of 1231 hospitals, only 491 (39.9 %) reported performing at least one NSM during the study period. Half of all NSMs were performed by the top 6 % (n = 30) of NSM-performing centers. NSM was associated with small tumor size (p < 0.001), lower tumor grades (p < 0.05), and negative nodal status (p < 0.001). However, half of NSM patients had at least one tumor characteristic that diverged from current (2016) NCCN recommendations for the procedure. CONCLUSIONS: The use of therapeutic NSM is increasing dramatically in the United States, despite recommendations that the procedure be used with caution. As NSM becomes increasingly common, efforts are needed to monitor its long-term oncologic outcomes and to ensure equitable access to it.

Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial.

BACKGROUND: Extremely premature (birth weight < 1250 g) infants are at high risk for acquiring late-onset sepsis and necrotizing enterocolitis, which are associated with significant mortality and morbidity. Own mother's milk contains protective (immune and trophic) biofactors which provide antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory functions, enhance intestinal microbiota, and promote intestinal maturation. Many of these biofactors are most highly concentrated in the milk expressed by mothers of extremely premature infants. However, since extremely premature infants do not receive oral milk feeds until 32 weeks post-conceptional age, they lack the potential benefit provided by milk (biofactor) exposure to oropharyngeal immunocompetent cells, and this deficiency could contribute to late-onset sepsis and necrotizing enterocolitis. Therefore, oropharyngeal administration of own mother's milk may improve the health outcomes of these infants. OBJECTIVES: To compare the effects of oropharyngeal administration of mother's milk to a placebo, for important clinical outcomes, including (1A) reducing the incidence of late-onset sepsis (primary outcome) and (1B) necrotizing enterocolitis and death (secondary outcomes). To identify the biomechanisms responsible for the beneficial effects of oropharyngeal mother's milk for extremely premature infants, including; (2A) enhancement of gastrointestinal (fecal) microbiota (2B) improvement in antioxidant defense maturation or reduction of pro-oxidant status, and (2C) maturation of immunostimulatory effects as measured by changes in urinary lactoferrin. METHODS/DESIGN: A 5-year, multi-center, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of oropharyngeal mother's milk to reduce the incidence of (1A) late-onset sepsis and (1B) necrotizing enterocolitis and death in a large cohort of extremely premature infants (n = 622; total patients enrolled). Enrolled infants are randomly assigned to one of 2 groups: Group A infants receive 0.2 mL of own mother's milk, via oropharyngeal administration, every 2 hours for 48 hours, then every 3 hours until 32 weeks corrected-gestational age. Group B infants receive a placebo (0.2 mL sterile water) following the same protocol. Milk, urine, oral mucosal swab, and stool samples are collected at various time points, before, during and after the treatment periods. Health outcome and safety data are collected throughout the infant's stay. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015.

Early National Experience with Laparoscopic Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Comparison of Laparoscopic Pancreaticoduodenectomy and Open Pancreaticoduodenectomy from the National Cancer Data Base.

BACKGROUND: There is considerable debate about the safety and clinical equivalence of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDCA). STUDY DESIGN: We queried the National Cancer Data Base to identify patients undergoing LPD and OPD for PDCA between 2010 and 2011. Chi-square and Student's t-tests were used to evaluate differences between the 2 approaches. Multivariable logistic regression modeling was performed to identify patient, tumor, or facility factors associated with perioperative mortality. RESULTS: Four thousand and thirty-seven (91%) patients underwent OPD. Three hundred and eighty-four (9%) patients underwent LPD. There were no statistical differences between the 2 surgical cohorts with regard to age, race, Charlson score, tumor size, grade, stage, or treatment with neoadjuvant chemoradiotherapy. Laparoscopic pancreaticoduodenectomy demonstrated a shorter length of stay (10 ± 8 days vs 12 ± 9.7 days; p < 0.0001) and lower rates of unplanned readmission (5% vs 9%; p = 0.027) than OPD. In an unadjusted comparison, there was no difference in 30-day mortality between the LPD and OPD cohorts (5.2% vs 3.7%; p = 0.163). Multivariable logistic regression modeling predicting perioperative mortality controlling for age, Charlson score, tumor size, nodal positivity, stage, facility type, and pancreaticoduodenectomy volume identified age (odds ratio [OR] = 1.05; p < 0.0001), positive margins (OR = 1.45; p = 0.030), and LPD (OR = 1.89; p = 0.009) as associated with an increased probability of 30-day mortality; higher hospital volume was associated with a lower risk of 30-day mortality (OR = 0.98; p < 0.0001). In institutions that performed ≥10 LPDs, the 30-day mortality rate of the laparoscopic approach was equal to that for the open approach (0.0% vs 0.7%; p = 1.00). CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is equivalent to OPD in length of stay, margin-positive resection, lymph node count, and readmission rate. There is a higher 30-day mortality rate with LPD, but this appears driven by a surmountable learning curve for the procedure.

Incidence and characteristics of patients presenting with acute myocardial infarction and non-obstructive coronary artery disease.

OBJECTIVES: This study aimed to characterize the etiologies of patients presenting with myocardial infarction (MI) and found to have non-obstructive coronary artery disease (NOCAD) and compare risk factors and in-hospital mortality to those with obstructive coronary artery disease (CAD). BACKGROUND: Patients presenting with an MI are often found to have NOCAD defined as less than 50% luminal diameter reduction by visual estimation on coronary angiography. METHODS: This study is a retrospective analysis of a total of 2,038 patients that presented to NorthShore University HealthSystem with MI and underwent coronary angiography from 2010 to 2013. RESULTS: 1,822 patients (89%) had CAD and 216 (11%) had NOCAD. Of the NOCAD patients, the most common etiologies were Takotsubo cardiomyopathy (28%), no alternative explanation (26%), demand ischemia (21%), myopericarditis (7%), coronary artery vasospasm (5%), and coronary artery dissection (3%). NOCAD patients were more likely to be younger and female. There was no significant difference between NOCAD and CAD patients in terms of in-hospital mortality (3.7% vs. 4.0% respectively, OR = 1.1, 95% CI 0.5-2.3, P = 0.83 by univariate logistic regression, OR = 1.2, 95% CI 0.5-3.1, P = 0.74 by multivariable analysis). CONCLUSIONS: CAD patients were more likely to have traditional risk factors of diabetes, hypertension, hypercholesterolemia, previous MI, previous revascularization with percutaneous coronary intervention or coronary artery bypass graft surgery. Patients presenting with MI and NOCAD were found to have several different etiologies on coronary angiography with the most common being Takotsubo cardiomyopathy.

Characteristics of Men Undergoing Testosterone Replacement Therapy and Adherence to Follow-up Recommendations in Metropolitan Multicenter Health Care System.

OBJECTIVE: To identify the frequencies of treatment and recommended laboratory follow-up for men with low serum testosterone levels. METHODS: The Electronic Data Warehouse was queried to identify men of ages 18-85 years, who obtained a testing for serum total testosterone level from 2009 to 2012. The frequency of testosterone replacement therapy (TRT), patient demographics, and clinical characteristics were collected. The frequency of follow-up with serum total testosterone and complete blood count levels was documented. RESULTS: Among 9176 men who underwent testing for low testosterone levels, 3320 (36%) of them were hypogonadal with a mean serum total testosterone level of 194.3 ± 64.9 ng/dL. Of them, 17.7% men were treated with TRTs. The treatment frequency significantly increased from 8.3% in 2009 to 24% in 2012. A total of 4.8% of men of reproductive ages (age, 18-35 years) were placed on TRTs. Within 180 days of initial testing, only 40% of treated men received follow-up with liver function tests and/or complete blood count, and only 49% had a follow-up serum testosterone level. CONCLUSION: Although the frequency of TRT is increasing, only a small percentage of hypogonadal men are actively undergoing treatment. A significant proportion of men of reproductive age are being treated with significant impacts on potential fertility. Less than half of the patients treated are being monitored appropriately after testosterone replacement. This highlights the importance of further education for providers prescribing testosterone replacement.

Are we testing appropriately for low testosterone?: Characterization of tested men and compliance with current guidelines.

INTRODUCTION: Direct-to-consumer ads for testosterone replacement therapies have significantly increased over the past several years. Subsequently, testing for low serum testosterone has correspondingly increased. AIMS: We sought to determine the testing behaviors of practitioners as well as the characteristics of men who are undergoing testing for low testosterone. METHODS: Men aged 18-85 years were queried from the institutional electronic data warehouse from 2009 to 2012. Men were considered "tested" if their serum total testosterone level had been measured for any purpose. Tested men (TM) were compared with those not tested (NT). MAIN OUTCOME MEASURES: The frequency and timing of testing for low testosterone as well as patient demographics and clinical characteristics were compared between TM and NT using multivariable logistic regression models. RESULTS: Of the 321,674 total men, 10,133 (3.2%) underwent testing with a serum total testosterone (mean age of 55.2 ± 14.1 years). The frequency of testing increased from 2.5% to 3.6% during the study period (P < 0.001). Multivariable analysis demonstrated that TM were significantly (P < 0.001) more likely to be Caucasian and have increased body mass index. In addition, TM were significantly more likely to have comorbid conditions including decreased libido (adjusted odds ratio [aOR] 10.0, 95% confidence interval [CI] 8.5, 11.7), infertility (aOR 4.8, 95% CI 3.6, 6.6), erectile dysfunction (aOR 3.6, 95% CI 3.4, 3.8), osteoporosis (aOR 3.3, 95% CI 2.8, 3.8), depression (aOR 1.7, 95% CI 1.6, 1.8), prostate cancer (aOR 1.7, 95% CI 1.5, 1.8), hypertension (aOR 1.3. 95% CI 1.2, 1.4), chronic obstructive pulmonary disease (aOR 1.2, 95% CI 1.0, 1.4), and benign prostatic hyperplasia (aOR 1.2, 95% CI 1.1, 1.2). Among TM, only 889 (9%) men underwent testing between 7 am and 12 pm. CONCLUSIONS: The rate of testosterone testing is increasing with most testing practices directed toward a subset of men with comorbidities that are associated with hypogonadism. Compliance of physicians obtaining early morning serum testosterone levels is low. Further education of practitioners is required to appropriately test patients for hypogonadism.

The prognostic significance of perineural invasion and race in men considering active surveillance.

OBJECTIVE: To determine the importance of perineural invasion (PNI) on diagnostic biopsy in men enrolled in active surveillance (AS). PATIENTS AND METHODS: Eligibility criteria for AS included clinical stage ≤ T2a and Gleason score ≤6, ≤3 cores positive, maximum single core involvement <50%, and total tumour volume ≤5% on diagnostic biopsy. All men received 12-core confirmation biopsy at ≤6 months. AS 'failure' on confirmatory biopsy was defined as failure to meet one or more eligibility criteria. Risk of AS failure was compared in men with and without PNI. RESULTS: For the 165 men comprising the study population, the mean (sd) age was 66.9 (6.5) years and the median (interquartile, IQR) PSA level of men at study entry was 4.4 (3.2-6.0) ng/mL. The median (IQR) follow-up was 5.5 (1.1-9.9) months. In all, 8.5% (14/165 men) had PNI on diagnostic biopsy. Compared with those without PNI, men with PNI tended to have more cores involved with cancer, at a mean (sd) of 2.0 (0.7) vs 1.6 (0.8) cores (P = 0.08) but did not have significantly a greater mean (sd) total tumour length on diagnostic biopsy, at 3.0 (2.1) vs 2.3 (3.6) mm (P = 0.27). Men with PNI on diagnostic biopsy were significantly more likely to meet criteria for disease progression on confirmatory biopsy (57% [8/14] vs 21% [32/151]; P = 0.006). PNI remained a significant predictor for AS failure after adjustment for number of positive cores, maximum percentage core involvement, and total tumour length (odds ratio 4.4, 95% confidence interval 1.4-14.2). CONCLUSIONS: PNI on diagnostic biopsy is associated with disease progression on confirmatory biopsy. The presence of PNI should factor into appropriate patient selection and counselling in AS.

Primary care physician PSA screening practices before and after the final U.S. Preventive Services Task Force recommendation.

OBJECTIVES: In May 2012, United States Preventive Services Task Force (USPSTF) finalized its recommendation against prostate-specific antigen (PSA) screening in all men. We aimed to assess trends in PSA screening frequency amongst primary care physicians (PCPs) surrounding the May 2012 USPSTF recommendation. METHODS AND MATERIALS: The electronic data warehouse was used to identify men aged between 40 and 79 years with no history of prostate cancer or urology visit who were evaluated by an internal medicine or family practice physician between 2007 and 2012. Analyses were directed toward PSA testing within 6-month time period from June to November, with particular focus on the 2011 (pre-USPSTF recommendation) and 2012 (post-USPSTF recommendation) cohorts. The primary outcome measure was proportion of men with at least 1 PSA test during the 6-month pre- and post-USPSTF recommendation periods. RESULTS: A total of 112,221 men met inclusion criteria. There was a significant decrease in screening frequency between the 2011 and 2012 cohorts (8.6% vs. 7.6%, P = 0.0001; adjusted odds ratio 0.89, 95% confidence interval 0.83-0.95). This decrease was most evident amongst patients aged 40 to 49 years (5.6% vs. 4.6%, P = 0.004) and 70 to 79 years (7.9% vs. 6.2%, P = 0.01). A significant decrease was also observed in patients with highest previous PSA value<1.0 (P<0.0001) and 1.0 to 2.49 ng/ml (P = 0.0074). CONCLUSIONS: Since the USPSTF recommendation was finalized, there is evidence of continuing decreases in PSA testing by PCPs. PCPs may be shifting toward more selective screening practices, as decreases in screening are most pronounced in the youngest and oldest patients and in those with history of PSA values<2.5 ng/ml.