Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model.

Small non-coding RNA [miRNA (microRNA)] found in the circulation have been used successfully as biomarkers and mechanistic targets for chronic and acute disease. The present study investigated the impact of age and sex on miRNA expression following ischaemic stroke in an animal model. Adult (6 month) and middle-aged (11-12 months) female and male rats were subject to MCAo (middle cerebral artery occlusion) using ET-1 (endothelin-1). Circulating miRNAs were analysed in blood samples at 2 and 5 days post-stroke, and brain miRNAs were analysed at 5 days post-stroke. Although stroke-associated infarction was observed in all groups, infarct volume and sensory-motor deficits were significantly reduced in adult females compared with middle-aged females, adult males or middle-aged males. At 2 days post-stroke, 21 circulating miRNAs were differentially regulated and PCA (principal component analysis) confirmed that most of the variance was due to age. At 5 days post-stroke, 78 circulating miRNAs exhibited significantly different regulation, and most of the variance was associated with sex. A small cohort (five) of miRNAs, miR-15a, miR-19b, miR-32 miR-136 and miR-199a-3p, were found to be highly expressed exclusively in adult females compared with middle-aged females, adult males and middle-aged males. Predicted gene targets for these five miRNAs analysed for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed that the top ten KEGG pathways were related to growth factor signalling, cell structure and PI3K (phosphoinositide 3-kinase)/Akt and mTOR (mammalian target of rapamycin) signalling. Overall, the pattern of circulating miRNA expression suggests an early influence of age in stroke pathology, with a later emergence of sex as a factor for stroke severity.

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study.

BACKGROUND: Durvalumab is approved for the treatment of adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This real-world study describes patient characteristics and durvalumab treatment patterns (number of doses and therapy duration; treatment initiation delays, interruptions, discontinuations, and associated reasons) among VHA-treated patients. METHODS: This was a retrospective cohort study of adults with unresectable stage III NSCLC receiving durvalumab at the VHA between 1 January 2017 and 30 June 2020. Patient characteristics and treatment patterns were presented descriptively. RESULTS: A total of 935 patients were included (median age: 69 years; 95% males; 21% Blacks; 46% current smokers; 16% ECOG performance scores ≥ 2; 50% squamous histology). Durvalumab initiation was delayed in 39% of patients (n = 367). Among the 200 patients with recorded reasons, delays were mainly due to physician preference (20%) and CRT toxicity (11%). Overall, patients received a median (interquartile range) of 16 (7-24) doses of durvalumab over 9.0 (2.9-11.8) months. Treatment interruptions were experienced by 19% of patients (n = 180), with toxicity (7.8%) and social reasons (2.6%) being the most cited reasons. Early discontinuation occurred in 59% of patients (n = 551), largely due to disease progression (24.2%) and toxicity (18.2%). CONCLUSIONS: These real-world analyses corroborate PACIFIC study results in terms of the main reasons for treatment discontinuation in a VHA population with worse prognostic factors, including older age, predominantly male sex, and poorer performance score. One of the main reasons for durvalumab initiation delays, treatment interruptions, or discontinuations was due to toxicities. Patients could benefit from improved strategies to prevent, identify, and manage CRT and durvalumab toxicities timely and effectively.

Clinicopathologic differences and mortality among Latinos and non-Latino whites with gastric cancer at a majority-minority cancer center in South Texas.

BACKGROUND: Latino patients have a higher incidence of gastric cancer compared to non-Latino white patients nationwide, with greater disparities in South Texas. However, the impact of Latino ethnicity on mortality in gastric cancer is controversial. We evaluated clinicopathological characteristics and survival outcomes in Latino vs. non-Latino white patients at our National Cancer Institute (NCI)-designated cancer center and its affiliated hospital. METHODS: We conducted a retrospective chart review of Latino and non-Latino white patients diagnosed with gastric cancer who were seen at Mays Cancer Center at the University of Texas Health in San Antonio, Texas, from 2000-2018. Median overall survival (mOS) was estimated from Kaplan-Meier curves and groups were compared with the log-rank test. RESULTS: A total of 193 patients met inclusion criteria and 65% (n=126) were Latino. Median age for all patients was 61 years. Female patients represented almost 50% of Latinos vs. 36% of non-Latino whites. There were no differences in Eastern Cooperative Oncology Group (ECOG) performance status, primary tumor location, stage, Helicobacter pylori status, HER2 status, or histologic subtype at diagnosis. Median overall survival was 14 months (95% CI: 13-36) for Latinos vs. 33 months (95% CI: 14 to n/a) for non-Latino whites (P=0.36). CONCLUSIONS: Compared to non-Latino white patients, Latino patients with gastric cancer at a majority-minority cancer center in South Texas did not have significant differences in baseline clinicopathologic features or survival outcomes. Further prospective studies are needed to evaluate epidemiologic, pathogenetic, and molecular differences in gastric cancer in order to identify variables associated with treatment efficacy and survival.