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Background: Robust and reliable prognosis prediction models have not been developed and validated for Asian patients with breast cancer, a rapidly growing yet understudied population in the United States.Methods: We used longitudinal data from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study (n = 5042), to develop prediction models for 5- and 10-year disease-free survival (DFS) and overall survival (OS). The initial models considered age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. We then evaluated whether the addition of modifiable lifestyle factors (physical activity, soy isoflavones intake, and postdiagnostic weight change) improved the models. All final models have been validated internally and externally in the National Cancer Database when applicable.Results: Our final models included age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, ER status, PR status, 6-month postdiagnostic weight change, interaction between ER status and tamoxifen therapy, and interaction between age and TNM stage. The internal validation yielded C-statistics of 0.76, 0.74, 0.78, and 0.75 for 5-year DFS, 10-year DFS, 5-year OS, and 10-year OS, respectively. The external validation yielded C-statistics of 5- and 10-year OS both at 0.78 for Chinese ethnicity, 0.79 for East Asian ethnicity, and 0.75 and 0.76 for all ethnic groups combined.Conclusion: We developed prediction models for breast cancer prognosis from a large prospective study. Our prognostic models performed very well in women from the United States-particularly in Asian American women-and demonstrated high prediction accuracy and generalizability. [ABSTRACT FROM AUTHOR]

Introduction: Social and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order.Methods: Adults, aged ≥18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015-2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1-3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1-3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates.Results: Of 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036).Conclusion: Question order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine-recommended questionnaire to capture SBDs. [ABSTRACT FROM AUTHOR]

Importance: Underutilization of guideline-directed medical therapy for heart failure with reduced ejection fraction is a major cause of poor outcomes. For many American Indian patients receiving care through the Indian Health Service, access to care, especially cardiology care, is limited, contributing to poor uptake of recommended therapy., Objective: To examine whether a telehealth model in which guideline-directed medical therapy is initiated and titrated over the phone with remote telemonitoring using a home blood pressure cuff improves guideline-directed medical therapy use (eg, drug classes and dosage) in patients with heart failure with reduced ejection fraction in Navajo Nation., Design, Setting, and Participants: The Heart Failure Optimization at Home to Improve Outcomes (Hózhó) randomized clinical trial was a stepped-wedge, pragmatic comparative effectiveness trial conducted from February to August 2023. Patients 18 years and older with a diagnosis of heart failure with reduced ejection fraction receiving care at 2 Indian Health Service facilities in rural Navajo Nation (defined as having primary care physician with 1 clinical visit and 1 prescription filled in the last 12 months) were enrolled. Patients were randomized to the telehealth care model or usual care in a stepped-wedge fashion, with 5 time points (30-day intervals) until all patients crossed over into the intervention. Data analyses were completed in January 2024., Intervention: A phone-based telehealth model in which guideline-directed medical therapy is initiated and titrated at home, using remote telemonitoring with a home blood pressure cuff., Main Outcomes and Measures: The primary outcome was an increase in the number of guideline-directed classes of drugs filled from the pharmacy at 30 days postrandomization., Results: Of 103 enrolled American Indian patients, 42 (40.8%) were female, and the median (IQR) age was 65 (53-77) years. The median (IQR) left ventricular ejection fraction was 32% (24%-36%). The primary outcome occurred significantly more in the intervention group (66.2% vs 13.1%), thus increasing uptake of guideline-directed classes of drugs by 53% (odds ratio, 12.99; 95% CI, 6.87-24.53; P < .001). The number of patients needed to receive the telehealth intervention to result in an increase of guideline-directed drug classes was 1.88., Conclusions and Relevance: In this heart failure trial in Navajo Nation, a telephone-based strategy of remote initiation and titration for outpatients with heart failure with reduced ejection fraction led to improved rates of guideline-directed medical therapy at 30 days compared with usual care. This low-cost strategy could be expanded to other rural settings where access to care is limited., Trial Registration: ClinicalTrials.gov Identifier: NCT05792085.

Purpose: Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer., Methods: Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) were randomly assigned 1:1 to arm A: cediranib 30 mg once daily plus olaparib 200 mg twice daily or arm B: olaparib 300 mg twice daily alone. The primary end point was radiographic progression-free survival (rPFS) in the intention-to-treat patients. The secondary end points were rPFS in patients with HRR-deficient and HRR-proficient mCRPC., Results: In the intention-to-treat set of 90 patients, median rPFS was 8.5 (95% CI, 5.4 to 12.0) and 4.0 (95% CI, 3.2 to 8.5) months in arms A and B, respectively. Cediranib/olaparib significantly improved rPFS versus olaparib alone (hazard ratio [HR], 0.617; 95% CI, 0.392 to 0.969; P = .0359). Descriptive analyses showed a median rPFS of 10.6 (95% CI, 5.9 to not assessed [NA]) and 3.8 (95% CI, 2.33 to NA) months (HR, 0.64; 95% CI, 0.272 to 1.504) among patients with HRR-deficient mCRPC, and 13.8 (95% CI, 3.3 to NA) and 11.3 (95% CI, 3.8 to NA) months (HR, 0.98; 95% CI, 0.321 to 2.988) among patients with BRCA2 -mutated mCRPC in arms A and B, respectively. The incidence of grades 3-4 adverse events was 61% and 18% in arms A and B, respectively., Conclusion: Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of grades 3-4 adverse events. BRCA2 -mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS.

To address the need for clinical investigators in oncology, American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) established the Methods in Clinical Cancer Research Workshop (MCCRW). The workshop's objectives were to: (i) provide training in the methods, design, and conduct of clinical trials; (ii) ensure that clinical trials met federal and international ethical guidelines; (iii) evaluate the effectiveness of the workshop; and (iv) create networking opportunities for young investigators with mentoring senior faculty. Educational methods included: (i) didactic lectures, (ii) Small Group Discussion Sessions, (iii) Protocol Development Groups, and (iv) one-on-one mentoring. Learning focused on the development of an Institutional Review Board (IRB)-ready protocol, which was submitted on the last day of the workshop. Evaluation methods included: (i) pre- and postworkshop tests, (ii) students' workshop evaluations, (iii) faculty's ratings of protocol development, (iv) students' productivity in clinical research after the workshop, and (v) an independent assessment of the workshop. From 1996 to 2014, 1,932 students from diverse backgrounds attended the workshop. There was a significant improvement in the students' level of knowledge from the pre- to the postworkshop exams ( P < 0.001). Across the classes, student evaluations were very favorable. At the end of the workshop, faculty rated 92% to 100% of the students' protocols as ready for IRB submission. Intermediate and long-term follow-ups indicated that more than 92% of students were actively involved in patient-related research, and 66% had implemented five or more protocols. This NCI-sponsored MCCRW has had a major impact on the training of clinicians in their ability to design and implement clinical trials in cancer research., (©2021 American Association for Cancer Research.)

Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients., Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence., Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression., Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access. This article is highlighted in the In This Issue feature, p. 1426 ., (©2020 American Association for Cancer Research.)

Introduction: Immune-related adverse event (IRAE) onset may represent a clinical biomarker for anti-programmed cell death protein 1 (PD-1) antibody response based on emerging evidence from patients with various advanced malignancies. This phenomenon has not been previously reported in a multidisease cohort of patients with gastrointestinal (GI) cancer with Food and Drug Administration (FDA)-approved indications to receive immune checkpoint inhibitor therapy., Materials and Methods: The study was a multicenter retrospective cohort analysis of 76 patients with GI cancer who had received anti-PD-1 antibodies for FDA-approved indications. The primary and secondary outcomes of the study were progression-free survival (PFS) and overall survival (OS) in patients based upon IRAE presence, respectively. PFS and OS were estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusted for IRAE onset, patient age, and enrolling institution was used to analyze outcomes., Results: Median PFS and OS were prolonged in patients who experienced IRAEs compared with those who did not experience them (PFS: not reached [NR] vs. 3.9 months [hazard ratio (HR) 0.13, 95% confidence interval (CI) 0.05-0.3, p < .001]; OS: NR vs. 7.4 months [HR 0.11, 95% CI 0.03-0.36, p < .001]). Among patients who experienced IRAEs, there were no significant differences in PFS and OS by either initial IRAE severity, management, or time to onset., Conclusion: Patients with gastrointestinal cancer who experienced IRAEs while on anti-PD-1 antibodies demonstrated significant improvements in PFS and OS compared with their counterparts who did not develop IRAEs. Although these findings add to results from studies in other tumor types, larger prospective studies are needed prior to clinical adoption of IRAE onset as a biomarker for immune checkpoint inhibitor response., Implications for Practice: Predictive clinical biomarkers for immune checkpoint inhibitor response have been understudied in the field of immuno-oncology. Immune-related adverse event onset appears to be one such biomarker. Across tumor types, immune-related adverse event onset has been associated with response to anti-programmed cell death protein 1 (PD-1) antibodies. The results of this study demonstrate this for the first time in patients with gastrointestinal cancer receiving anti-PD-1 antibodies. Before immune-related adverse event onset can be adopted clinically as a predictive biomarker for immune checkpoint inhibitor response, however, larger prospective studies are needed to better understand the nuances between immune-related adverse event characteristics (severity, site, management, timing of onset) and immune checkpoint inhibitor effectiveness., (© AlphaMed Press 2020.)

Background: Early palliative care (PC) improves quality of life and prolongs survival for patients with metastatic non-small cell lung cancer (NSCLC). Despite these benefits, patient- and provider-specific barriers lead to underutilization of PC. To investigate these barriers, this 2 part study surveyed United States oncologists and patients with NSCLC., Patients and Methods: Oncologists in the International Association for the Study of Lung Cancer membership directory were surveyed on referral practice and attitudes regarding the role of PC for patients with NSCLC. Patients with advanced NSCLC at the Vanderbilt Ingram Cancer Center were surveyed separately regarding their understanding of PC and factors influencing them to seek referral., Results: Of 279 oncologists, 93 responded. Eighty-three percent believe definitive evidence exists supporting early PC; however, in practice, oncologists only refer an average of 19% of patients at diagnosis. Reasons for not referring included lack of symptoms (56%), belief that oncologists can manage PC independently (46%), not wanting to burden patients with appointments (41%), concern that referral may not be well received (38%), and long wait times (20%). Of 100 patients with NSCLC, 64% were unfamiliar with PC. Six percent had seen a PC provider. Ninety-eight percent of patients would accept referral if recommended by their oncologist. Patients desired referral for uncontrolled pain (95%), weak support system (86%), other cancer-related symptoms (85%), goals of care discussion (76%), and depression/anxiety (76%)., Conclusion: Although most oncologists acknowledge benefits of early PC for patients with metastatic NSCLC, a minority of patients are referred. Few patients with NSCLC are familiar with PC, but most are interested in referral., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Accredited breast centers in the United States are measured on performance of breast conservation surgery (BCS) in the majority of women with early-stage breast cancer. Prior research in regional and limited national cohorts suggests a recent shift toward increasing performance of mastectomy in patients eligible for BCS., Objective: To examine whether mastectomy rates in patients eligible for BCS are increasing over time nationwide, and are associated with coincident increases in breast reconstruction and bilateral mastectomy for unilateral disease., Design, Setting, and Participants: We performed a retrospective cohort study of temporal trends in performance of mastectomy for early-stage breast cancer using multivariable logistic regression modeling to adjust for pertinent covariates and interactions. We studied more than 1.2 million adult women treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from January 1, 1998, to December 31, 2011, using the National Cancer Data Base., Exposures: Year of breast cancer diagnosis., Main Outcomes and Measures: Proportion of women with early-stage breast cancer who underwent mastectomy. Secondary outcome measures include temporal trends in breast reconstruction and bilateral mastectomy for unilateral disease., Results: A total of 35.5% of the study cohort underwent mastectomy. The adjusted odds of mastectomy in BCS-eligible women increased 34% during the most recent 8 years of the cohort, with an odds ratio of 1.34 (95% CI, 1.31-1.38) in 2011 relative to 2003. Rates of increase were greatest in women with clinically node-negative disease (odds ratio, 1.38; 95% CI, 1.34-1.41) and in situ disease (odds ratio, 2.05; 95% CI, 1.95-2.15). In women undergoing mastectomy, rates of breast reconstruction increased from 11.6% in 1998 to 36.4% in 2011 (P < .001 for trend). Rates of bilateral mastectomy for unilateral disease increased from 1.9% in 1998 to 11.2% in 2011 (P < .001)., Conclusions and Relevance: In the past decade, there have been marked trends toward higher proportions of BCS-eligible patients undergoing mastectomy, breast reconstruction, and bilateral mastectomy. The greatest increases are seen in women with node-negative and in situ disease. Mastectomy rates do not yet exceed current American Cancer Society/American College of Surgeons Commission on Cancer accreditation benchmarks. Further research is needed to understand factors associated with these trends and their implications for performance measurement in American Cancer Society/American College of Surgeons Commission on Cancer centers.

Objective: The use of evidence-based guidelines can improve the care for asthma patients. We implemented a computerized asthma management system in a pediatric emergency department (ED) to integrate national guidelines. Our objective was to determine whether patient eligibility identification by a probabilistic disease detection system (Bayesian network) combined with an asthma management system embedded in the workflow decreases time to disposition decision., Methods: We performed a prospective, randomized controlled trial in an urban, tertiary care pediatric ED. All patients 2-18 years of age presenting to the ED between October 2010 and February 2011 were screened for inclusion by the disease detection system. Patients identified to have an asthma exacerbation were randomized to intervention or control. For intervention patients, asthma management was computer-driven and workflow-integrated including computer-based asthma scoring in triage, and time-driven display of asthma-related reminders for re-scoring on the electronic patient status board combined with guideline-compliant order sets. Control patients received standard asthma management. The primary outcome measure was the time from triage to disposition decision., Results: The Bayesian network identified 1339 patients with asthma exacerbations, of which 788 had an asthma diagnosis determined by an ED physician-established reference standard (positive predictive value 69.9%). The median time to disposition decision did not differ among the intervention (228 min; IQR=(141, 326)) and control group (223 min; IQR=(129, 316)); (p=0.362). The hospital admission rate was unchanged between intervention (25%) and control groups (26%); (p=0.867). ED length of stay did not differ among intervention (262 min; IQR=(165, 410)) and control group (247 min; IQR=(163, 379)); (p=0.818)., Conclusions: The control and intervention groups were similar in regards to time to disposition; the computerized management system did not add additional wait time. The time to disposition decision did not change; however the management system integrated several different information systems to support clinicians' communication., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

The northern leopard frog (Rana pipiens or Lithobates pipiens) is historically found in most of the provinces of Canada and the northern and southwest states of the United States. In the last 50 years, populations have suffered significant losses, especially in the western regions of the species range. Using a peptidomics approach, we show that the pattern of expressed antimicrobial skin peptides of frogs from three geographically separated populations are distinct, and we report the presence of four peptides (brevinin-1Pg, brevinin-1Pl, ranatuerin-2Pb, and ranatuerin-2Pc) that have not previously been found in skin secretions. The differences in expressed peptides reflect differences in the distribution of alleles for the newly described Brevinin1.1 locus in the three populations. When enriched peptide mixtures were tested for their ability to inhibit growth of the pathogenic amphibian chytrid (Batrachochytrium dendrobatidis), peptides from Minnesota or Vermont frogs were more effective that peptides from Michigan frogs. Four of the purified peptides were tested for their ability to inhibit growth of two bacterial pathogens (Aeromonas hydrophila and Staphylococcus epidermidis) and B. dendrobatidis. Three of the four were effective inhibitors of B. dendrobatidis and S. epidermidis, but none inhibited A. hydrophila. We interpret these differences in expression and activity of antimicrobial peptides as evidence to suggest that each population may have been selected to express a suite of peptides that reflects current and past encounters with skin microbes.

Background: Increasing evidence suggests significant disparity in colorectal cancer outcomes between black and white patients. Contributing factors may include advanced tumor stage at diagnosis, differences in treatment, more aggressive tumor biology, access to care, and patient comorbidity., Hypothesis: Disparities in colorectal cancer outcomes exist despite similar objective measures of treatment., Design and Setting: Ten-year retrospective review of all patients with colorectal cancer using tumor registries at a city hospital (n = 83) and a university medical center (n = 585) in the same city. We assessed stage at diagnosis; curative surgical resection; use of adjuvant treatment; overall, disease-free, and stage-specific survival; and socioeconomic status. Patients with nonwhite, nonblack ethnicity (4% overall) were excluded. Differences in stage and treatments were compared using the chi(2) test, and median survival rates were compared using log-rank tests., Results: Significantly more black patients were treated at the city hospital (53.0%) vs the university medical center (10.6%) (P<.001). No differences were identified in stage distribution or treatments received between hospitals or between black and white patients. Significantly worse survival was noted among patients treated at the city hospital (2.1 vs 5.3 years; P<.001) and among black patients treated at both institutions (city hospital: 1.4 vs 2.1 years, and university hospital: 3.2 vs 5.7 years; P<.001 for both). Disease-free survival rates showed similar significant reductions for black patients at both institutions. There was no association between survival and socioeconomic status at either institution., Conclusion: The marked reductions in overall and disease-free survival for black patients with colorectal cancer do not seem to be related to variation in treatment but may be due to biologic factors or non-cancer-related health conditions.