ABSTRACT Background Lung cancer (LC) and respiratory failure (RF) are leading causes of adult mortality worldwide. Analyzing long‐term mortality trends across demographic, racial, geographic, and socioeconomic groups is essential to address disparities and enhance outcomes. This study investigates US national mortality patterns for LC and RF from 1999 to 2023, focusing on changes in age‐adjusted mortality rates (AAMRs) and key disparities. Methods Mortality data from the CDC WONDER database (1999–2023) for adults aged 25+ with LC (ICD‐10: C34) or RF (ICD‐10: J96) were analyzed. AAMRs per 100,000 were calculated, stratified by gender, race/ethnicity, region, state, and urban–rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes (APCs) with 95% confidence intervals (CIs), with significance at p < 0.05. Results Over 1999–2023, 456,325 deaths from LC and RF were recorded. AAMRs declined from 1999 to 2010 (APC = −1.2, 95% CI: −1.6 to −0.9) but rose from 2010 to 2023 (APC = 1.4, 95% CI: 1.1–1.7). Men's AAMRs steadily decreased, whereas women's dropped initially, then increased from 2011 to 2023 (APC = 2.0, 95% CI: 1.7 to 2.5). Non‐Hispanic Whites saw a sharp AAMR rise from 2014 to 2017 (APC = 2.7, 95% CI: 0.9 to 3.3), with other racial/ethnic groups showing mixed trends. Regionally, the Northeast had the highest AAMRs (8.6, 95% CI: 8.5 to 8.7), and the Midwest the lowest (7.1, 95% CI: 7.0 to 7.1). Metropolitan areas saw increases post‐2006, whereas nonmetropolitan areas rose after 2009 (APC = 2.3, 95% CI: 1.8–3.1). Mississippi had the highest state AAMR (14.0, 95% CI: 13.7–14.4), Wisconsin the lowest (3.7, 95% CI: 3.5–3.8). Conclusion LC and RF mortality declined until 2010, then increased, revealing significant disparities. Targeted interventions are critical to address these trends and reduce inequities.

ABSTRACTPurposeTo assess the long‐term effects of a community cancer exercise program on quality of life, fatigue, weight, waist circumference, physical activity levels, lower extremity strength, body mass index (BMI), heart rate, and blood pressure, across non‐metastatic and metastatic patients.MethodsA total of 918 participants (F/M: 1.77; mean age = 61 years, SD = 13.233) diagnosed with cancer within the last five years completed a 12‐session guided physical activity program. Sessions included functional, aerobic, and resistance training aligned with ACSM guidelines for cancer patients. Blood pressure, quality of life, fatigue, BMI, lower extremity strength, body weight, and physical activity levels were measured at baseline, 12 sessions, and at 6 months, and 12 months during follow‐up. The Wilcoxon signed‐rank test was used to assess changes over time.ResultsSignificant improvements were observed in physical activity levels, health‐related quality of life, and overall quality of life, sustained at 6‐ and 12‐month follow‐ups. Waist circumference, fatigue, and blood pressure significantly decreased across all time points. Lower extremity strength improved up to 6 months but was not significant at 12 months. No significant changes were observed in body weight or BMI. Non‐metastatic patients experienced significant improvements in blood pressure, waist circumference, fatigue, and functional ability, while metastatic patients maintained their baseline health measures, suggesting a stabilizing effect.ConclusionsThis study demonstrates that a community‐based exercise program benefits non‐metastatic cancer patients by improving quality of life, physical activity levels, and functional health, while helping metastatic patients maintain health outcomes. These findings highlight the importance of structured exercise programs in cancer care and support their implementation in real‐world settings.

ABSTRACTBackgroundAging significantly affects the structural and functional integrity of the blood–brain barrier (BBB), increasing the susceptibility of the central nervous system (CNS) to both primary and metastatic cancers. As the BBB deteriorates, it promotes tumor cell infiltration, alters drug permeability, and contributes to a proinflammatory microenvironment that supports tumor progression. These age‐related changes present major obstacles in the effective treatment of CNS malignancies in elderly patients.MethodsThis review synthesizes current literature on the mechanisms of BBB aging and its impact on CNS cancer development and treatment. It examines key structural alterations, such as tight junction protein loss, endothelial dysfunction, and pericyte reduction, as well as functional changes including impaired immune regulation and transporter dysfunction. The review also evaluates therapeutic challenges and emerging strategies to overcome the BBB barrier in the aging brain.ResultsAging induces BBB dysfunction by weakening cellular junctions, disrupting the neurovascular unit, and promoting chronic neuroinflammation. These alterations facilitate tumor cell entry and survival in the brain and reduce the effectiveness of cancer therapies due to impaired drug delivery. Promising interventions, including nanoparticle‐based therapies, focused ultrasound techniques, and targeted chemoimmunotherapy, are under development to enhance therapeutic outcomes in elderly patients.ConclusionThe age‐related breakdown of the BBB contributes significantly to increased cancer risk and therapeutic resistance in the CNS. Addressing BBB dysfunction through age‐specific interventions and advanced drug delivery strategies is critical to improving outcomes for older adults with CNS malignancies. Further research into the molecular pathways of BBB aging will support the development of personalized and effective treatments.

Background:Bladder cancer is one of the top 10 cancers diagnosed in Americans with a median age of 73. This is the patient population that tends to be older with multiple medical conditions, and previously described variability in treatment in the earlier stages of the disease. This study aimed to evaluate the first-line therapeutic choices for older adults newly diagnosed with advanced bladder cancer. In addition, this work evaluated predictors of response as well as the role of events of functional importance in relation to treatment assignment.Methods:A population-based cohort study was conducted using the SEER-Medicare database of patients with advanced stage bladder cancer not eligible for curative intent therapy between 2010 and 2013. Patient groups of interest were compared via univariate and multivariate associations. Additionally, a latent class analysis was applied to identify classes with similar features in reference to events of functional importance—events linked to the maintenance or improvement of physical function status.Results:Within the sample, we noted that a minority of patients received a standard cisplatin-containing regimen (14.77%) and a majority did not receive any chemotherapy (59.69%). Most patients were over age 75. The adjusted odds ratio of no chemo versus cisplatin in patients aged 76 and older compared to patients 66–75 was 6.61 (4.79–9.13; p < 0.0001). We applied latent class analysis methods to the dataset, and three classes demonstrated very low and moderate levels of functional events in the 12 months prior to a person’s first outpatient visit for advanced bladder cancer care.Conclusions:Patients with new diagnosis of advanced bladder cancer largely do not receive the recommended first-line systemic therapy of cisplatin chemotherapy, and a significant majority does not receive any treatment. When evaluating the association between class assignment and predictors of chemotherapy use, such as comorbidity and age, patients with “low usage overall” were more likely to receive chemotherapy. Yet even patients who received chemotherapy had some events of functional importance.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, and age is by far the greatest risk factor for developing CVD. Vascular dysfunction, including endothelial dysfunction and arterial stiffening, is responsible for much of the increase in CVD risk with aging. A key mechanism involved in vascular dysfunction with aging is oxidative stress, which reduces the bioavailability of nitric oxide (NO) and induces adverse changes to the extracellular matrix of the arterial wall (e.g., elastin fragmentation/degradation, collagen deposition) and an increase in advanced glycation end products, which form crosslinks in arterial wall structural proteins. Although vascular dysfunction and CVD are most prevalent in older adults, several conditions can "accelerate" these events at any age. One such factor is chemotherapy with anthracyclines, such as doxorubicin (DOXO), to combat common forms of cancer. Children, adolescents and young adults treated with these chemotherapeutic agents demonstrate impaired vascular function and an increased risk of future CVD development compared with healthy age-matched controls. Anthracycline treatment also worsens vascular dysfunction in mid-life (50-64 years of age) and older (65 and older) adults such that endothelial dysfunction and arterial stiffness are greater compared to age-matched controls. Collectively, these observations indicate that use of anthracycline chemotherapeutic agents induce a vascular aging-like phenotype and that the latter contributes to premature CVD in cancer survivors exposed to these agents. Here, we review the existing literature supporting these ideas, discuss potential mechanisms as well as interventions that may protect arteries from these adverse effects, identify research gaps and make recommendations for future research.

In comparison to the contemporary approach to multiple myeloma, personalized treatment has the potential to guide more efficient drug selection and disease targeting. Although three drug regimens have repeatedly proven superior in this disease, older adults often receive two drugs to minimize treatment-related toxicities. Consequently, older adults are at risk to receive less effective treatment, contributing to their currently inferior outcomes. Here, we discuss Myeloma Drug Sensitivity Testing (My-DST) as an approach to personalized treatment for Multiple Myeloma by distinguishing relative drug sensitivity (S) versus resistance (R) to the commonly used drugs for this malignancy. Through personalized therapy to optimize the ratio of effective drugs, older persons stand to derive the most benefit if we can minimize poor responses and side effects, simultaneously improving survival and quality of life (QOL) outcomes.

Yap and Taz are co-transcription factors that have been implicated in the development of many cancers. Here, we review the literature that analyzes the function of Yap/Taz in normal breast and breast cancer contexts. Our review of the literature suggests that that Yap and Taz are involved in breast cancer and Taz, in particular, is involved in the triple negative subtype. Nevertheless, the precise contexts in which Yap/Taz contribute to specific breast cancer phenotypes remains unclear. Indeed, Yap/Taz dysregulation acts differentially and in multiple epithelial cell types during early breast cancer progression. We propose Yap/Taz activation promotes breast cancer phenotypes in breast cancer precursor cells. Further, Yap dysregulation as a result of aging in breast tissue may result in microenvironments that increase the fitness of breast cancer precursor cells relative to the normal epithelia. <PE-FRONTEND>.