Heterogeneities of the impact of public health policies on HIV/AIDS indicators in Brazil according to sociodemographic factors: A real-life study.

INTRODUCTION: The impact of specific policies on HIV care has been scarcely investigated. In this study we aimed to analyze the impact of the Treatment For All policy (TFA-2013) and the adoption of integrase strand transfer inhibitors (INSTIs-2017) as first-line therapy on clinical indicators of people living with HIV (PLHIV) in Brazil. METHODS: We assessed the public database of Brazil's Ministry of Health and extracted data from 2009 to 2019. We investigated the impact of TFA and INSTIs with a time-series analysis of four health indicators in PLHIV: antiretroviral treatment (ART) initiation with a CD4+ count >500/mm3 ; ART initiation <1 month after the first CD4+ measurement; viral load suppression (VLS); and treatment adherence. We explored trends over time by gender, age, macroregion of residency and municipal-level social vulnerability index. RESULTS: We included 753 316 PLHIV in 2019. Most were males (64.81%) in the 30-49 years age category (50.86%). We observed an overall improvement in all HIV clinical indicators, with notable impact of TFA on timely ART initiation and VLS, and mild impact of INSTIs on treatment adherence. Such improvements were heterogeneous, with remarkable gaps in gender, age and socioeconomic groups that have persisted over time. Indicators point to inferior outcomes among children, older adults, women and people living in socially vulnerable locations. CONCLUSIONS: Recent Brazilian public policies have had positive impacts on key HIV clinical indicators. However, our results highlight the need for specific policies to improve HIV care for children, older adults, women and socially vulnerable groups.

Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer.

BACKGROUND: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. METHODS: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. RESULTS: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population's 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. CONCLUSIONS: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

Social Determinants of Health and Racial Disparities in Cardiac Events in Breast Cancer.

BACKGROUND: Racial disparities have been reported for breast cancer and cardiovascular disease (CVD) outcomes. The determinants of racial disparities in CVD outcomes are not yet fully understood. We aimed to examine the impact of individual and neighborhood-level social determinants of health (SDOH) on the racial disparities in major adverse cardiovascular events (MACE; consisting of heart failure, acute coronary syndrome, atrial fibrillation, and ischemic stroke) among female patients with breast cancer. METHODS: This 10-year longitudinal retrospective study was based on a cancer informatics platform with electronic medical record supplementation. We included women aged ≥18 years diagnosed with breast cancer. SDOH were obtained from LexisNexis, and consisted of the domains of social and community context, neighborhood and built environment, education access and quality, and economic stability. Race-agnostic (overall data with race as a feature) and race-specific machine learning models were developed to account for and rank the SDOH impact in 2-year MACE. RESULTS: We included 4,309 patients (765 non-Hispanic Black [NHB]; 3,321 non-Hispanic white). In the race-agnostic model (C-index, 0.79; 95% CI, 0.78-0.80), the 5 most important adverse SDOH variables were neighborhood median household income (SHapley Additive exPlanations [SHAP] score [SS], 0.07), neighborhood crime index (SS = 0.06), number of transportation properties in the household (SS = 0.05), neighborhood burglary index (SS = 0.04), and neighborhood median home values (SS = 0.03). Race was not significantly associated with MACE when adverse SDOH were included as covariates (adjusted subdistribution hazard ratio, 1.22; 95% CI, 0.91-1.64). NHB patients were more likely to have unfavorable SDOH conditions for 8 of the 10 most important SDOH variables for the MACE prediction. CONCLUSIONS: Neighborhood and built environment variables are the most important SDOH predictors for 2-year MACE, and NHB patients were more likely to have unfavorable SDOH conditions. This finding reinforces that race is a social construct.

Adjuvant Therapy in Breast Cancer Patients With Microscopic Residual Disease.

INTRODUCTION: Surgical resection is the gold standard for early-stage breast cancer. Positive surgical margins are associated with poor outcome. Endocrine therapy (ET) is recommended as primary systemic treatment for hormone receptor positive (HR+) breast cancer after surgery. We hypothesized that chemoenocrine therapy (CET) would not be associated with improved survival relative to ET for patients with positive margins. MATERIALS AND METHODS: The National Cancer Database was queried for pathologic stage I HR + HER2-breast cancer patients treated with partial mastectomy and adjuvant whole-breast irradiation between 2004 and 2017. The adjuvant treatment approaches to positive surgical margins were investigated and compared. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression. RESULTS: Among 228,453 patients, a positive surgical margin (microscopic residual disease, R1) was identified in 3561 (1.6%) patients. Compared with complete resections, positive margin was associated with inferior overall survival (hazard ratio [HR] = 1.276, P = 0.003). Among the R1 patients, 78.7% received ET only, 11.7% received CET, 1.2% received chemotherapy only, and 8.5% received no systemic therapy. After controlling for patient, facility, and tumor characteristics, ET provided greatest survival benefit (relative to no therapy, HR = 0.378, P < 0.001) followed by CET (HR = 0.446, P = 0.020). Compared with ET alone, CET is not associated with additional overall survival benefit (HR = 1.179, P = 0.595). CONCLUSIONS: CET appeared not to be associated with an improved overall survival in early stage HR + HER2-breast cancer with microscopic residual disease relative to ET. Positive surgical margins therefore are probably not a relevant clinical factor for adjuvant chemotherapy decision-making.

A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis.

BACKGROUND: Small invasive breast cancers (BCs) with tumor sizes ≤5 mm (T1a) are associated with an excellent prognosis without systemic therapy. Although HER2 overexpression (HER2+) is associated with a higher risk of recurrence and poorer clinical outcomes, in the absence of HER2 directed therapy, it remains unclear whether adjuvant systemic therapy is necessary in node-negative patients diagnosed with HER2+ invasive BCs ≤5 mm (pT1aN0M0). METHODS: The National Cancer Database was searched to identify patients diagnosed with HER2+ pT1aN0M0 BCs from 2004 to 2017. The cohort was stratified by treatment status: local therapy alone or local plus adjuvant systemic therapy. A 1:1 propensity match was performed. Overall survival (OS) was analyzed using stratified multivariable Cox proportional hazards regression analyses. RESULTS: Of the 8948 patients found, 4026 (45.0%) underwent surgery alone, and 4922 (55.0%) received surgery plus systemic therapy. Patients with either moderately differentiated (odds ratio [OR], 2.053; P < .001) or poorly/undifferentiated tumors (OR, 3.780; P < .001) or with the presence of lymphovascular invasion (OR, 3.351; P < .001) were more likely to have received systemic therapy. Propensity matching generated 1162 pairs of patients who were hormone receptor positive (HR+) and 748 pairs who were hormone receptor negative (HR-). Propensity matching effectively reduced selection bias between study groups. In the matched cohort, the addition of systemic therapy was not associated with superior OS (hazard ratio for HR+, 1.613; P = .107, and hazard ratio for HR- 1.319; P = .369) compared with patients who received local therapy alone. CONCLUSIONS: In pT1aN0M0 HER2+ BC, the addition of adjuvant systemic therapy after surgical excision was not associated with improved OS compared with local therapy alone.

Adjuvant trastuzumab with or without chemotherapy in stage 1 pT1N0 HER2+ breast cancer: a National Cancer Database analysis.

PURPOSE: Approximately 20% of all breast cancers (BC) are HER2 amplified. In the APT trial, weekly paclitaxel/trastuzumab in node negative HER2+ BC with tumors < 3 cm was associated with a 7-year invasive disease-free survival of 93%. However, this was in the context of a non-randomized trial, and for pT1N0 HER2+ BC it remains unclear whether HER2 monotherapy would provide similar clinical outcomes to chemo-HER2 therapy. We hypothesized that adjuvant chemo-HER2 therapy would be associated with a modestly improved overall survival compared to HER2 monotherapy in patients with tumors < 2 cm. METHODS: In the National Cancer Database (2004-2017), patients with a primary diagnosis of pT1N0M0 HER2+ BC, were separated into two groups: (i) HER2 monotherapy, i.e., trastuzumab, and (ii) chemo-HER2 therapy. A 3:1 propensity match was performed to balance patient selection bias between the two different cohorts. Long-term overall survival (OS) was compared between both groups. RESULTS: A total of 23,281 patients met the criteria. 22,268 (96.7%) received chemo-HER2 therapy and 1013 (4.4%) received HER2 monotherapy. Propensity match identified 1995 patients who received chemo-HER2 therapy, and 666 who received HER2 monotherapy. After matching, adjuvant chemo-HER2 therapy was associated with a modest survival advantage over HER2 monotherapy (5-year OS 94.1% vs. 90.6%, P = 0.041). CONCLUSIONS: Even though there is a modest OS advantage favoring adjuvant chemo-HER2 therapy in patients with pT1N0 HER2+ BC, HER2 monotherapy was associated with 5-year OS > 90%. Therefore, in select patients who have contraindications for cytotoxic chemotherapy, or decline adjuvant chemotherapy altogether, adjuvant trastuzumab monotherapy appears to be a reasonable alternative.

Epidemiology of Abdominal Aortic Aneurysm Repair in Brazil from 2008 to 2019 and Comprehensive Review of Nationwide Statistics Across the World.

INTRODUCTION: Studying epidemiology of abdominal aortic aneurysms repairs is essential to prevent related deaths. Although outcomes are influenced by socioeconomic factors, there are no nationwide studies on these statistics in low-and-middle income countries. Therefore, we designed this study to evaluate abdominal aortic aneurysms repair rates, trends, costs, and in-hospital mortality in the Brazilian Public Health System, which exclusively insures over 160 million Brazilians. MATERIAL AND METHODS: Retrospective cross-sectional population-based analysis of publicly available data referring to all abdominal aortic aneurysm repairs performed between 2008 and 2019 in Brazilian public hospitals. RESULTS: We observed a total of 13,506 abdominal aortic aneurysm repairs, of which 32% were emergency endovascular repairs, 20% emergency open repairs, 32% elective endovascular repairs and 16% elective open repairs. There has been a downward trend in total abdominal aortic aneurysms repairs and an increasing predominance of endovascular repair. Elective and endovascular repairs were significantly associated with lower in-hospital mortality. For ruptured abdominal aortic aneurysms, we observed mortality rates of 13.8% after endovascular repair and 52.1% after open repair. For intact abdominal aortic aneurysms, we observed mortalities of 3.8% after endovascular repair and 18.6% after open repair. Procedure and mortality rates varied significantly among the Brazilian regions. CONCLUSIONS: We observed a low and decreasing rate of abdominal aortic aneurysm repair. Most repairs were emergency and endovascular and there was an increasing predominance of endovascular repair. Endovascular and elective repairs were associated with lower mortality.

Temporal trends in vena cava filter implantation in public health system inpatients: an 11-year analysis of the largest city in Brazil.

Background: Vena cava filter implantation is considered a simple procedure, which can lead to overuse and over-indication. It is nevertheless associated with short and long-term complications. Objectives: The goals of this study were to evaluate rates of vena cava filter implantation conducted by Brazil's Unified Public Health System, analyzing in-hospital mortality and migration of patients from other cities seeking medical attention in São Paulo. Methods: This study analyzed all vena cava filter procedures conducted from 2008 to 2018 in the city of São Paulo and registered on the public database using a big data system to conduct web scraping of publicly available databases. Results: A total of 1324 vena cava filter implantations were analyzed. 60.5% of the patients were female; 61.7% were under 65 years old; 34.07% had registered addresses in other cities or states; and there was a 7.4% in-hospital mortality rate. Conclusions: We observed an increase in the rates of use of vena cava filters up to 2010 and a decrease in rates from that year onwards, which coincides with the year that the Food and Drug Administration published a recommendation to better evaluate vena cava filter indications.

Contexto: O implante de filtro de veia cava é considerado um procedimento de baixa complexidade, o que pode resultar em indicação excessiva. No entanto, não é isento de complicações a curto e longo prazo. Objetivos: Avaliar as taxas de implantes de filtro de veia cava realizados pelo Sistema Único de Saúde e a origem geográfica e mortalidade intra-hospitalar dos pacientes. Métodos: Foi conduzida uma análise em um banco de dados públicos referente às taxas de implantes de filtro de veia cava realizados de 2008 a 2018 na cidade de São Paulo, utilizando o sistema de big data. Resultados: Foram analisados 1.324 implantes de filtro de veia cava financiados pelo Sistema Único de Saúde. Identificou-se tendência de aumento da taxa de implantação até 2010 e de redução dos números após esse período. Do total de pacientes, 60,5% eram do sexo feminino; 61,75% tinham menos de 65 anos; e 34,07% possuíam endereço oficial em outra cidade ou estado. A taxa de mortalidade intra-hospitalar foi de 7,4%. Conclusões: Observamos aumento das taxas de implante de filtro de veia cava até 2010 e redução das taxas após esse período, o que coincide com o ano em que a organização norte-americana Food and Drug Administration publicou uma recomendação para melhor avaliar as indicações de filtros.

Surgical repair of abdominal aortic aneurysms on the public health system in the largest city in Brazil: a descriptive analysis of in-hospital data on 2693 procedures over 10 years.

Background: From 1990 to 2015, mortality from aortic aneurysms increased 16.8% in Brazil. São Paulo is the largest city in Brazil and about 5 million people depend on the public health system there. Objectives: To conduct an epidemiological analysis of abdominal aortic aneurysm surgeries in the city of São Paulo. Methods: Infra-renal aortic aneurysm procedures performed over a decade (from 2008 to 2017) were studied using publicly-available platforms from the Unified Health System and DATASUS. Results: 2693 procedures were analyzed; 66.73% were endovascular; 78.7% of patients were male; 70.7% were aged 65 years or more; 64.02% were elective hospital admissions. There were 288 in-hospital deaths (mortality: 10.69%). In-hospital mortality was lower for endovascular surgery than for open surgery; both for elective (4.13% versus 14.42%) and urgent (9.73% versus 27.94%) (p = 0.019) admissions. The highest volume hospital (n = 635) had the lowest in-hospital mortality (3.31%). USD 24,835,604.84 was paid; an average of $ 2,318.63 for elective open, $ 3,420.10 for emergency open, $ 12,157.35 for elective endovascular and $ 12,969.12 for urgent endovascular procedures. Endovascular procedure costs were statistically higher than the values paid for open surgeries (p <0.001). Conclusions: Endovascular surgeries were performed twice as often as open surgeries; they had shorter hospital stays and lower mortality.

Contexto: No Brasil, a mortalidade por aneurisma de aorta aumentou 16,8% de 1990 a 2015. São Paulo é a maior cidade do Brasil, e cerca de 5 milhões de pessoas dependem do sistema público de saúde. Objetivos: Análise epidemiológica das cirurgias do aneurisma de aorta abdominal na cidade de São Paulo. Métodos: As cirurgias para correção do aneurisma de aorta infrarrenal realizadas no período de uma década (de 2008 a 2017) foram estudadas utilizando-se plataformas publicamente disponíveis do Sistema Único de Saúde e do Departamento de Informática do Sistema Único de Saúde. Resultados: Foram analisados ​​2.693 procedimentos, entre os quais 66,73% eram endovasculares. Entre os pacientes, houve predominância do sexo masculino (78,7%) e daqueles com 65 anos ou mais (70,7%). Um total de 64,02% eram admissões hospitalares eletivas. Ocorreram 288 óbitos hospitalares (mortalidade: 10,69%). A mortalidade durante a internação foi menor para cirurgia endovascular do que para cirurgia aberta tanto no contexto eletivo (4,13% versus 14,42%) quanto urgente (9,73% versus 27,94%) (p = 0,019). O maior volume (n = 635) apresentou menor mortalidade intra-hospitalar (3,31%). Foi pago um total de $24.835.604,84, sendo uma média de $2.318,63 para cirurgia abertura eletiva, $3.420,10 para cirurgia abertura de emergência, $12.157,35 para cirurgia endovascular eletiva e $12.969,12 para cirurgia endovascular na urgência. Os custos dos procedimentos endovasculares foram estatisticamente superiores aos valores pagos para as cirurgias abertas (p < 0,001). Conclusões: Foram realizadas duas vezes mais cirurgias endovasculares do que abertas, as quais apresentaram menor tempo de internação e menor mortalidade.

Epidemiological analysis of lower limb revascularization for peripheral arterial disease over 12 years on the public healthcare system in Brazil.

Background: Worldwide, peripheral arterial disease (PAD) is a disorder with high morbidity, affecting more than 200 million people. Objectives: Our objective was to analyze surgical treatment for PAD provided on the Brazilian Public Healthcare System over 12 years using publicly available data. Methods: The study was conducted with analysis of data available on the Brazilian Health Ministry's database platform, assessing distributions of procedures and techniques over the years and their associated mortality and costs. Results: A total of 129,424 procedures were analyzed (performed either for claudication or critical ischemia, proportion unknown). The vast majority of procedures were endovascular (65.49%) and this disproportion exhibited a rising trend (p<0.001). There were 3,306 in-hospital deaths (mortality of 2.55%), with lower mortality in the endovascular group (1.2% vs. 5.0%, p=0.008). The overall governmental expenditure on these procedures was U$ 238,010,096.51, and endovascular procedures were on average significantly more expensive than open surgery (U$ 1,932.27 vs. U$ 1,517.32; p=0.016). Conclusions: Lower limb revascularizations were performed on the Brazilian Public Healthcare System with gradually increasing frequency from 2008 to 2019. Endovascular procedures were vastly more common and were associated with lower in-hospital mortality rates, but higher procedure costs.

Contexto: A doença arterial periférica (DAP) é uma doença com alta morbidade global, afetando mais de 200 milhões de pessoas. Objetivos: Neste estudo, analisamos o tratamento cirúrgico para DAP no sistema público de saúde do Brasil no período de 12 anos, com base em dados publicamente disponíveis. Métodos: O estudo foi conduzido a partir da análise de dados disponíveis na plataforma do Departamento de Informática do Sistema Único de Saúde (DATASUS), do Ministério da Saúde, avaliando a distribuição da técnica cirúrgica utilizada, a mortalidade e o custo ao longo dos anos. Resultados: Um total de 129.424 procedimentos foram analisados (para claudicantes e isquemia crítica, em proporção desconhecida). A maiora dos procedimentos foi via endovascular (65,49%), com tendência de aumento nessa desproporção (p < 0,001). Houve 3.306 mortes intra-hospitalares (mortalidade de 2,55%) com menor mortalidade no grupo endovascular (1,2% vs. 5,0%; p = 0,008). O investimento governamental total para esses procedimentos foi de US$ 238.010.096,51, e os procedimentos endovasculares foram significativamente mais caros que a cirurgia aberta convencional (US$ 1.932,27 vs. US$ 1.517,32; p = 0,016). Conclusões: No sistema público de saúde brasileiro, as revascularizações de membros inferiores ocorreram com frequência crescente entre 2008 e 2019. Os procedimentos endovasculares foram mais comuns e relacionados a menor mortalidade intra-hospitalar, mas a maiores custos.

Lower Limb Revascularization for Peripheral Arterial Disease in 10,951 Procedures over 11 years in a Public Health System: A Descriptive Analysis of the Largest Brazilian City.

BACKGROUND: Worldwide, peripheral arterial disease (PAD) is a disease with high morbidity, affecting more than 200 million people. Our objective was to analyze the surgical treatment for PAD performed in the Unified Health System of the city of São Paulo during the last 11 years based on publicly available data. METHODS: The study was conducted with data analysis available on the TabNet platform, belonging to the DATASUS. Public data (government health system) from procedures performed in São Paulo between 2008 and 2018 were extracted. Sex, age, municipality of residence, operative technique, number of surgeries (total and per hospital), mortality during hospitalization, mean length of stay in the intensive care unit and amount paid by the government system were analyzed. RESULTS: A total of 10,951 procedures were analyzed (either for claudicants or critical ischemia-proportion unknown); 55.4% of the procedures were performed on males, and in 50.60%, the patient was older than 65 years. Approximately two-thirds of the patients undergoing these procedures had residential addresses in São Paulo. There were 363 in-hospital deaths (mortality of 3.31%). The hospital with the highest number of surgeries (n = 2,777) had lower in-hospital mortality (1.51%) than the other hospitals. A total of $20,655,272.70 was paid for all revascularizations. CONCLUSIONS: Revascularization for PAD treatment has cost the government system more than $20 million over 11 years. Endovascular surgeries were performed more often than open surgeries and resulted in shorter hospital stays and lower perioperative mortality rates.

Epidemiological Analysis of Carotid Artery Stenosis Intervention during 10 years in the Public Health System in the Largest City in Brazil: Stenting Has Been More Common than Endarterectomy.

BACKGROUND: Stroke is the second leading cause of death worldwide with approximately 5.7 million cases/year, and carotid atherosclerosis accounts for 10 to 20% of cases. METHODS: In Brazil, the Unified Health System (Sistema Único de Saúde [SUS]) is a tax-funded public health care system that provides care for roughly half the population. São Paulo is the eighth largest city in the world with an estimated population of over 12 million people, of whom more than 5 million rely solely on SUS. This study aimed to describe rates of carotid artery stenting (CAS) and carotid endarterectomy (CEA) performed between 2008 and 2017 in the city of São Paulo through web scraping of publicly available databases. RESULTS: Three thousand seven hundred and four carotid revascularization procedures were performed between 2008 and 2017, of which 2,432 were CAS (65.7%). Rates of CAS ranged from 59.9% in 2016 to 86% in 2011. There were 57 in-hospital deaths (1.54%), 34 after CAS (1.4%; 34/2,432) and 23 after CEA (1.81%; 23/1,272) (P = 0.562). SUS reimbursements were US $7,862,017.09 (81.44% of all reimbursements) for 2,432 CAS procedures and US $1,792,324.06 (18.56%) for 1,272 CEA procedures. Average SUS reimbursement for CAS (US $3,232.73) was more than double than that for CEA (US $1,409.05). CONCLUSIONS: In a city whose population exceeds that of some European countries, costs of CAS and CEA to the public health care system totaled more than US$ 9 million over 10 years. Epidemiologically, CAS was performed more commonly than CEA with no difference in in-hospital mortality between CAS and CEA, but reimbursements were 2.29 times higher for CAS. The low adoption of CEA in São Paulo is in contrast to countries where utilization rates are higher for CEA than for CAS.

Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer.

PURPOSE: A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy. PATIENTS AND METHODS: Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation. ORR was assessed using a binomial distribution. Survival was analyzed via the Kaplan-Meier method. Bulk RNA sequencing was employed for correlative studies. RESULTS: Thirty patients were enrolled. The ORR was 48.0%: 2 (7%) complete responses (CR), 11 (41%) partial responses (PR), and 8 (30%) stable disease (SD). The median DOR for patients with CR or PR was 6.4 months [95% confidence interval (CI), 4-8.5 months]. For patients with CR, DOR was >24 months. Overall median PFS and OS were 5.8 (95% CI, 4.7-8.5 months) and 13.4 months (8.9-17.3 months), respectively. We identified unique transcriptomic landscapes associated with each RECIST category of radiographic treatment response. In CR and durable PR, IGHG1 expression was enriched. IGHG1high tumors were associated with improved OS (P = 0.045) and were concurrently enriched with B cells and follicular helper T cells, indicating IGHG1 as a promising marker for lymphocytic infiltration and robust response to chemo-immunotherapy. CONCLUSIONS: Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy.

Adjuvant chemotherapy is associated with an overall survival benefit regardless of age in ER+/HER2- breast cancer pts with 1-3 positive nodes and oncotype DX recurrence score 20 to 25: an NCDB analysis.

Background: The RxPONDER trial found that among breast cancer patients with estrogen receptor positive (ER+) breast cancer, 1-3 positive axillary nodes, and a recurrence score of ≤25, only pre-menopausal women benefitted from adjuvant chemoendocrine therapy; postmenopausal women with similar characteristic did not benefit from adjuvant chemotherapy. We aimed to replicate the RxPonder trial using a larger patient cohort with real world data to determine whether a RS threshold existed where adjuvant chemotherapy was beneficial regardless of age. Methods: The National Cancer Database (NCDB) was queried for women with ER+, human epidermal growth factor receptor 2 (HER2) negative breast cancer, 1-3 positive axillary nodes, and RS ≤25 who received endocrine (ET) only or chemo-endocrine therapy (CET). Cox regression interaction was explored between CET and age as a surrogate for menopausal status. Results: The final analytic cohort included 28,427 eligible women: 7,487 (26.3%) received adjuvant CET and 20,940 (73.7%) ET. In the entire cohort, RS had a normal distribution, with a median score of 14. After correcting for demographic and clinical variables, a threshold effect was observed with RS >20 being associated with a significantly inferior overall survival (OS) (P value range: < 0.001-0.019). In women with RS of 20-25, CET was associated with a significant improvement in OS compared to ET alone, regardless of age (age <=50: HR = 0.334, P=0.002; age>50: HR=0.521, P=0.019). Conclusion: Among women with ER+/HER2- breast cancer with 1-3 positive nodes, and a RS of 20-25-in contrast to the RxPONDER trial-we observed that CET was associated with an OS benefit in women regardless of age.

Estimating the overall survival benefit of adjuvant chemo-endocrine therapy in women over age 50 with pT1-2N0 early stage breast cancer and 21-gene recurrence score ≥26: A National Cancer Database analysis.

BACKGROUND: Validation studies of the 21-gene recurrence score (RS) previously demonstrated that adjuvant chemotherapy plus endocrine therapy (CET) was associated with a significant survival benefit in women with node negative breast cancer (BC) and RS >31. However, the TAILORx trial, did not quantify the benefit of adjuvant CET in older women with node negative hormone receptor positive (HR+) BC with RS ≥26. We hypothesized that CET would be associated with improved overall survival (OS) compared to endocrine therapy (ET) in women >50 with HR+/HER2-node negative BC and RS ≥26. METHODS: The National Cancer Database (NCDB) was queried to identify women >50 with RS ≥26 ER+/HER2-BC pT1-2N0M0. Chi-square and logistic regression analysis determined the difference between ET and CET. OS was analyzed using a multivariable Cox model. RESULTS: We included 16,745 women-4740 (28.3%) received ET and 12,005 (71.7%) received CET. Women who received CET had: moderately (OR = 1.853, p < 0.001) or poorly/undifferentiated tumors (OR = 3.875, p < 0.001), pT2 (OR = 1.356, p < 0.001), or lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates were significantly superior in women receiving CET vs. ET alone (95.4% vs. 92.0%, Hazard Ratio = 0.680, p < 0.001). CONCLUSIONS: We observed that CET was associated with a clinically and statistically significant higher OS compared to ET alone in women >50 years of age with RS ≥26 pT1 and pT2 N0M0 HR+/HER2-breast cancer, and which suggests that cytotoxic chemotherapy has an impact on reducing mortality that is independent of induction of premature ovarian failure.

Racial disparities in breast cancer treatment patterns and treatment related adverse events.

The main objective of this work was to perform a comprehensive analysis and provide a race-stratified epidemiological report accounting for differences in treatment patterns and treatment related adverse events in Non-Hispanic women with breast cancer (BC). The cohort included women ≥ 18 years diagnosed with in-situ, early-stage, and late-stage BC (2005-2022). Treatment patterns included: surgery, breast radiation, chemotherapy, endocrine therapy, or biologic therapy. Treatment related adverse events were: chemotherapy complications, cardiovascular toxicities, immune-related adverse events, psychological affectations, or cognitive decline/dementia. The influence of race on the outcomes was measured via Cox proportional-hazards models. We included 17,454 patients (82% non-Hispanic Whites [NHW]). Most of the patients had a Charlson Comorbidity Score between 1 and 2 (68%), and TNM stage I (44.5%). Surgery was performed in 51.5% of the cases, while 30.6% received radiotherapy, 26.4% received chemotherapy, 3.1% received immunotherapy, and 41.2% received endocrine therapy. Non-Hispanic Blacks (NHB) had a lower probability of undergoing breast cancer surgery (aHR = 0.92, 95% CI 0.87-0.97) and of being prescribed endocrine therapy (aHR = 0.83, 95% CI 0.79-0.89), but a higher probability of receiving adjuvant radiotherapy (aHR = 1.40, 95% CI 1.29-1.52). Moreover, NHBs had lower risk of being diagnosed with psychological issues (aHR = 0.71, 95% CI 0.63-0.80) but a higher risk for cognitive decline/dementia (aHR = 1.30, 95% CI 1.08-1.56). In conclusion, NHB women diagnosed with BC were less likely than NHW to undergo curative intent surgery or receive endocrine therapy, and had a higher risk of cognitive decline/dementia after cancer treatment. Public policy measures are urgently needed which equalize access to quality healthcare for all patients and that promote a learning healthcare system which can improve cancer outcomes.

Thirty-Day Unplanned Hospital Readmissions in Patients With Cancer and the Impact of Social Determinants of Health: A Machine Learning Approach.

PURPOSE: Develop a cancer-specific machine learning (ML) model that accurately predicts 30-day unplanned readmissions in patients with solid tumors. METHODS: The initial cohort included patients 18 years or older diagnosed with a solid tumor. Two distinct cohorts were generated: one with and one without detailed social determinants of health (SDOHs) data. For each cohort, data were temporally partitioned in 70% (training), 20% (validation), and 10% (testing). Tree-based ML models were developed and validated on each cohort. The metrics used to evaluate the model's performance were receiver operating characteristic curve (ROC), area under the ROC curve, precision, recall (R), accuracy, and area under the precision-recall curve. RESULTS: We included 13,717 patients in this study in two cohorts (5,059 without SDOH data and 8,658 with SDOH data). Unplanned 30-day readmission occurred in 21.3% of the cases overall. The five main non-SDOH factors most highly associated with an unplanned 30-day readmission (R, 0.74; IQR, 0.58-0.76) were: number of previous unplanned readmissions; higher Charlson comorbidity score; nonelective index admission; discharge to anywhere other than home, hospice, or nursing facility; and higher anion gap during the admission. Neighborhood crime index, neighborhood median home values, annual income, neighborhood median household income, and wealth index were the main five SDOH factors important for predicting a high risk for an unplanned hospital readmission (R, 0.66; IQR, 0.56-0.72). The models were not directly comparable. CONCLUSION: Key drivers of unplanned readmissions in patients with cancer are complex and involve both clinical factors and SDOH. We developed a cancer-specific ML model that with reasonable accuracy identified patients with cancer at high risk for an unplanned hospital readmission.

Sex differences in adults with acute myeloid leukemia and the impact of sex on overall survival.

BACKGROUND: There is a male predominance of acute myeloid leukemia (AML) incidence, but survival data are conflicting. The objective of this study is to carry out a comprehensive analysis of sex differences in AML, and to investigate the impact of sex disparities in survival. METHODS: The cohort included patients ≥18 years diagnosed with AML (2010-2022). Demographics, treatment patterns, treatment adverse events, and survival were analyzed. The population was described and compared by sex, and sex-based risks and associations were obtained via Cox proportional-hazards regression. RESULTS: In total, 1020 AML patients were analyzed (57.4% males), with lower risk of death for females (aHR = 0.41, 95% CI 0.26-0.66). Among females, BMT (aHR = 0.51, 95% CI 0.27-0.97), hospitalization record (aHR = 0.65, 95%CI 0.45-0.93), and higher appointment completion rates (aHR = 0.98, 95% CI 0.98-0.98) were associated with lower risk of death. Overall, and similarly in males, higher age at diagnosis (aHR = 1.03, 95% CI 1.02-1.04) and a TP53 mutation (aHR = 2.24, 95% CI 1.69-2.97) were associated with higher risk of death. CONCLUSION: Sex differences exist in both AML incidence and overall survival. Treatment and health care factors should be addressed by caregivers and public policies developed to reduce mortality rates and mitigate existing sex differences.

Social Determinants of Health Data Improve the Prediction of Cardiac Outcomes in Females with Breast Cancer.

Cardiovascular disease is the leading cause of mortality among breast cancer (BC) patients aged 50 and above. Machine Learning (ML) models are increasingly utilized as prediction tools, and recent evidence suggests that incorporating social determinants of health (SDOH) data can enhance its performance. This study included females ≥ 18 years diagnosed with BC at any stage. The outcomes were the diagnosis and time-to-event of major adverse cardiovascular events (MACEs) within two years following a cancer diagnosis. Covariates encompassed demographics, risk factors, individual and neighborhood-level SDOH, tumor characteristics, and BC treatment. Race-specific and race-agnostic Extreme Gradient Boosting ML models with and without SDOH data were developed and compared based on their C-index. Among 4309 patients, 11.4% experienced a 2-year MACE. The race-agnostic models exhibited a C-index of 0.78 (95% CI 0.76-0.79) and 0.81 (95% CI 0.80-0.82) without and with SDOH data, respectively. In non-Hispanic Black women (NHB; n = 765), models without and with SDOH data achieved a C-index of 0.74 (95% CI 0.72-0.76) and 0.75 (95% CI 0.73-0.78), respectively. Among non-Hispanic White women (n = 3321), models without and with SDOH data yielded a C-index of 0.79 (95% CI 0.77-0.80) and 0.79 (95% CI 0.77-0.80), respectively. In summary, including SDOH data improves the predictive performance of ML models in forecasting 2-year MACE among BC females, particularly within NHB.