Time Kills: Impact of Socioeconomic Deprivation on Timely Access to Guideline-Concordant Treatment in Foregut Cancer.

BACKGROUND: Receipt of guideline-concordant treatment (GCT) is associated with improved prognosis in foregut cancers. Studies show that patients living in areas of high neighborhood deprivation have worse healthcare outcomes; however, its effect on GCT in foregut cancers has not been evaluated. We studied the impact of the area deprivation index (ADI) as a barrier to GCT. STUDY DESIGN: A single-institution retrospective review of 498 foregut cancer patients (gastric, pancreatic, and hepatobiliary adenocarcinoma) from 2018 to 2022 was performed. GCT was defined based on National Comprehensive Cancer Network guidelines. ADI, a validated measure of neighborhood disadvantage was divided into terciles (low, medium, and high) with high ADI indicating the most disadvantage. RESULTS: Of 498 patients, 328 (66%) received GCT: 66%, 72%, and 59% in pancreatic, gastric, and hepatobiliary cancers, respectively. Median (interquartile range) time from symptoms to workup was 6 (3 to 13) weeks, from diagnosis to oncology appointment was 4 (1 to 10) weeks, and from oncology appointment to treatment was 4 (2 to 10) weeks. Forty-six percent were diagnosed in the emergency department. On multivariable analyses, age 75 years or older (odds ratio [OR] 0.39 [95% CI 0.18 to 0.87]), Black race (OR 0.52 [95% CI 0.31 to 0.86]), high ADI (OR 0.25 (95% CI 0.14 to 0.48]), 6 weeks or more from symptoms to workup (OR 0.44 [95% CI 0.27 to 0.73]), 4 weeks or more from diagnosis to oncology appointment (OR 0.76 [95% CI 0.46 to 0.93]), and 4 weeks or more from oncology appointment to treatment (OR 0.63 [95% CI 0.36 to 0.98]) were independently associated with nonreceipt of GCT. CONCLUSIONS: Residence in an area of high deprivation predicts nonreceipt of GCT. This is due to multiple individual- and system-level barriers. Identifying these barriers and developing effective interventions, including community outreach and collaboration, leveraging telehealth, and increasing oncologic expertise in underserved areas, may improve access to GCT.

Association between Rural Residence and Processes of Care in Pancreatic Cancer Treatment.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is an aggressive malignancy associated with poor outcomes. Surgical resection and receipt of multimodal therapy have been shown to improve outcomes in patients with potentially resectable PDAC; however treatment and outcome disparities persist on many fronts. The aim of this study was to analyze the relationship between rural residence and receipt of quality cancer care in patients diagnosed with non-metastatic PDAC. METHODS: Using the National Cancer Database, patients with non-metastatic pancreatic cancer were identified from 2006-2016. Patients were classified as living in metropolitan, urban, or rural areas. Multivariable logistic regression was used to identify predictors of cancer treatment and survival. RESULTS: A total of 41,786 patients were identified: 81.6% metropolitan, 16.2% urban, and 2.2% rural. Rural residing patients were less likely to receive curative-intent surgery (p = 0.037) and multimodal therapy (p < 0.001) compared to their metropolitan and urban counterparts. On logistic regression analysis, rural residence was independently associated with decreased surgical resection [OR 0.82; CI 95% 0.69-0.99; p = 0.039] and multimodal therapy [OR 0.70; CI 95% 0.38-0.97; p = 0.047]. Rural residence independently predicted decreased overall survival [OR 1.64; CI 95% 1.45-1.93; p < 0.001] for all patients that were analyzed. In the cohort of patients who underwent surgical resection, rural residence did not independently predict overall survival [OR 0.97; CI 95% 0.85-1.11; p = 0.652]. CONCLUSIONS: Rural residence impacts receipt of optimal cancer care in patients with non-metastatic PDAC but does not predict overall survival in patients who receive curative-intent treatment.

MicroRNA-like snoRNA-Derived RNAs (sdRNAs) Promote Castration-Resistant Prostate Cancer.

We have identified 38 specifically excised, differentially expressed snoRNA fragments (sdRNAs) in TCGA prostate cancer (PCa) patient samples as compared to normal prostate controls. SnoRNA-derived fragments sdRNA-D19b and -A24 emerged among the most differentially expressed and were selected for further experimentation. We found that the overexpression of either sdRNA significantly increased PC3 (a well-established model of castration-resistant prostate cancer (CRPC)) cell proliferation, and that sdRNA-D19b overexpression also markedly increased the rate of PC3 cell migration. In addition, both sdRNAs provided drug-specific resistances with sdRNA-D19b levels correlating with paclitaxel resistance and sdRNA-24A conferring dasatinib resistance. In silico and in vitro analyses revealed that two established PCa tumor suppressor genes, CD44 and CDK12, represent targets for sdRNA-D19b and sdRNA-A24, respectively. This outlines a biologically coherent mechanism by which sdRNAs downregulate tumor suppressors in AR-PCa to enhance proliferative and metastatic capabilities and to encourage chemotherapeutic resistance. Aggressive proliferation, rampant metastasis, and recalcitrance to chemotherapy are core characteristics of CRPC that synergize to produce a pathology that ranks second in cancer-related deaths for men. This study defines sdRNA-D19b and -A24 as contributors to AR-PCa, potentially providing novel biomarkers and therapeutic targets of use in PCa clinical intervention.

Rise of the phoenix: Mucormycosis in COVID-19 times.

PURPOSE: Rhino-orbital mucormycosis in times of ongoing COVID-19 pandemic. AIMS: The aim of the study was to document cases of rhino-orbital mucormycosis seen at our Regional Institute of Ophthalmology during COVID-19 (coronavirus disease 2019) times. METHODS: The study is a retrospective, institutional cohort, interventional study. It was carried out at our Regional Institute of Ophthalmology from September 2020 to mid-March 2021. All patients of biopsy-proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated via a multidisciplinary approach with intravenous liposomal amphotericin B and debridement of local necrotic tissue. Exenteration was done when indicated. A minimum 75-day follow-up period was accorded to all study patients. Statistical analysis was done using Chi-square test. A P value ≤0.05 was taken as significant. RESULTS: Thirty-one patients were seen, with a mean age of 56.3 years. The major risk factors included uncontrolled diabetes (96.7%) and COVID-19 positivity (61.2%), with concomitant steroid use in 61.2% patients. The most common presentation was diminution of vision (<6/60 in 80.64% patients) and ophthalmoplegia (77.4%). The most common imaging findings were orbital cellulitis (61.29%) and pansinusitis (77.4%). Intravenous liposomal amphotericin B was given to all patients for an average 18.93 days. Exenteration was required in (n = 4) 12.9% of cases. Twenty-eight patients recovered and were alive on follow-up. Mortality was seen in three patients. The presence of cerebral involvement and a HbA1c value of ≥8 were found to be significant in the prediction of survival of patients with mucormycosis. CONCLUSION: We present the largest institutional cohort of rhino-orbital mucormycosis patients during the ongoing COVID-19 pandemic era from our unique perspective.

Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma.

Metabolic reprogramming has been described in rapidly growing tumors, which are thought to mostly contain fast-cycling cells (FCCs) that have impaired mitochondrial function and rely on aerobic glycolysis. Here, we characterize the metabolic landscape of glioblastoma (GBM) and explore metabolic specificities as targetable vulnerabilities. Our studies highlight the metabolic heterogeneity in GBM, in which FCCs harness aerobic glycolysis, and slow-cycling cells (SCCs) preferentially utilize mitochondrial oxidative phosphorylation for their functions. SCCs display enhanced invasion and chemoresistance, suggesting their important role in tumor recurrence. SCCs also demonstrate increased lipid contents that are specifically metabolized under glucose-deprived conditions. Fatty acid transport in SCCs is targetable by pharmacological inhibition or genomic deletion of FABP7, both of which sensitize SCCs to metabolic stress. Furthermore, FABP7 inhibition, whether alone or in combination with glycolysis inhibition, leads to overall increased survival. Our studies reveal the existence of GBM cell subpopulations with distinct metabolic requirements and suggest that FABP7 is central to lipid metabolism in SCCs and that targeting FABP7-related metabolic pathways is a viable therapeutic strategy.