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Objectives: The objective of this study is to validate a hypothesis that a non-invasive optical imaging assay targeting genomic VPAC receptors on malignant cells shed in voided urine will represent either benign prostatic hyperplasia (BPH) or prostatic cancer (PCa). Risk for BPH in men 50-70 years old is 50-70% and PCa is 17%. BPH and PCa can coexist in 20% of men with BPH. Most commonly practiced methods to diagnose BPH do not distinguish BPH from PCa. Patients or Materials and Methods: Males with BPH (N = 97, 60.8 ± 6.3 years, prostate-specific antigen 0.7 ± 0.4 ng/mL) and without oncologic disease (N = 35, 63.4 ± 5.8 years, prostate-specific antigen < 1.5 ng/mL) signed informed consent form and provided voided urine. Urine was cytocentrifuged, cells collected on glass slide, fixed, treated with VPAC specific fluorophore TP4303 (Kd 3.1 × 10-8M), washed, incubated with DAPI and observed using a fluorescence microscope. Cells with no VPAC did not fluoresce (BPH) and those with VPAC had red-orange fluorescence (PCa). Real-time polymerase chain reaction analyses for VPAC and NKX3.1 assay for cell origin were performed. Results: Eighty-seven subjects were negative for VPAC expression. Positive VPAC expression was noted in 10 subjects. Patient chart review for clinical data on these 10 VPAC positive subjects showed five had nephrolithiasis, three had renal cysts, one had prostatitis and one was being treated with finasteride. Real-time polymerase chain reaction analysis-VPAC expressions for 7 normal and 12 BPH subjects were 1.31 ± 1.26 and 0.94 ± 0.89, respectively (P = 0.46). NKX3.1 showed cells of prostate origin for finasteride-treated patient. Specificity for VPAC urine assay for excluding prostate cancer in this BPH cohort was 88.5%, positive predictive value 0.00% and negative predictive value 100%. Conclusion: VPAC assay may contribute extensively for BPH diagnosis and warrant continued investigation.
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INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous tumor among American men. Androgen receptor signaling inhibitors such as abiraterone and enzalutamide have been approved for similar disease states among patients with advanced PCa. Existing data suggest using steroids is associated with an increased risk of infection. Because abiraterone is usually prescribed with prednisone, we sought to compare the risk of septicemia in patients using abiraterone vs. enzalutamide. MATERIALS AND METHODS: We utilized the SEER-Medicare-linked data and used negative binomial regression models to compare the changes in the rates of septicemia-related hospitalizations six months pre- and post-abiraterone and enzalutamide initiation. RESULTS: We found that the incidence of septicemia-related hospitalizations increased 2.77 fold within six months of initiating abiraterone (incidence rate ratio [IRR]: 2.77, 95% confidence interval [CI]: 2.17-3.53) 1.97 fold within six months of starting enzalutamide (IRR: 1.97, 95% CI: 1.43-2.72). However, the difference in the changes did not reach statistical significance (interaction IRR: 0.71, 95% CI: 0.48-1.06). DISCUSSION: The findings suggest that both abiraterone and enzalutamide are associated with an increased risk of septicemia-related hospitalizations. However, the difference in the increase of septicemia risk following the two treatments did not reach statistical significance. Further studies are warranted to understand the mechanisms at play.
Subject(s)
Androstenes , Benzamides , Nitriles , Phenylthiohydantoin , Sepsis , Humans , Male , Phenylthiohydantoin/therapeutic use , Phenylthiohydantoin/analogs & derivatives , Phenylthiohydantoin/adverse effects , Nitriles/therapeutic use , Benzamides/therapeutic use , Sepsis/epidemiology , Sepsis/chemically induced , Aged , Androstenes/therapeutic use , Androstenes/adverse effects , Aged, 80 and over , United States/epidemiology , Hospitalization/statistics & numerical data , SEER Program , Prostatic Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Incidence , MedicareABSTRACT
PURPOSE: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services. METHODS: Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers. RESULTS: The analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was -0.04 (one-sided 95% CI, -∞ to 2.54; P = .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm. CONCLUSION: The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.
Subject(s)
Genetic Counseling , Prostatic Neoplasms , Humans , Male , Genetic Counseling/methods , Genetic Testing , Germ Cells , Health Knowledge, Attitudes, Practice , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/therapyABSTRACT
BACKGROUND: Germline testing is important in prostate cancer and evaluation can be complex. METHODS: We instituted a monthly multi-disciplinary virtual genetics tumor board (7/2021-3/2022). Participants and panelists were surveyed on usefulness and acceptability. RESULTS: 101 participants attended a session, and 77 follow-up surveys were completed. Over 90% participants and 100% panelists endorsed usefulness of the case discussions and usability of the technology. The majority felt it provided new information they will use. CONCLUSIONS: A multidisciplinary genetics board was successfully developed to address complexity in prostate cancer genetics. The virtual platform may enhance dissemination of expertise where there are regional gaps.
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BACKGROUND AND AIMS: The objective of this study is to determine the diagnostic accuracy of the American College of Radiology Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System LR-5 characterization for HCC diagnosis in North American or European patients. APPROACH AND RESULTS: A prospective multinational cohort study was performed from January 2018 through November 2022 at 11 academic and nonacademic centers in North America and Europe. Patients at risk for HCC with at least 1 liver observation not previously treated, identified on ultrasound (US), or multiphase CT or MRI performed as a part of standard clinical care were eligible for the study. All participants were examined with CEUS of the liver within 4 weeks of CT/MRI or tissue diagnosis to characterize up to 2 liver nodules per participant using ACR CEUS Liver Imaging Reporting and Data System. Definite HCC diagnosis on the initial CT/MRI, imaging follow-up, or histology for CT/MRI-indeterminate nodules were used as reference standards. A total of 545 nodules had confirmed reference standards in 480 patients, 73.8% were HCC, 5.5% were other malignancies, and 20.7% were nonmalignant. The specificity of CEUS LR-5 for HCC was 95.1% (95% CI 90.1%-97.7%), sensitivity 62.9% (95% CI 57.9%-67.7%), positive predictive value 97.3% (95% CI 94.5%-98.7%), and negative predictive value 47.7% (95% CI 41.7%-53.8%). In addition, benign CEUS characterization (LR-1 or LR-2) had 100% specificity and 100% positive predictive value for nonmalignant liver nodules. CONCLUSIONS: CEUS Liver Imaging Reporting and Data System provides an accurate categorization of liver nodules in participants at risk for HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Prospective Studies , Cohort Studies , Contrast Media , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging/methods , Europe , North America , Sensitivity and SpecificityABSTRACT
Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Contrast Media , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Prospective Studies , Treatment Outcome , Young Adult , AdultABSTRACT
An anomalous origin of the right coronary artery from the opposite sinus of Valsalva with an intramural course (R-ACAOS-IM) may cause sudden cardiac death in children and adolescents. However, the natural history and management of patients in whom this anomaly is detected later during adulthood remains uncertain. The goals of this study were to assess the impact of an R-ACAOS-IM on the clinical outcomes in an adult population and to determine if adult patients with this anomaly who do not have significant coronary artery disease (CAD) can be managed safely without surgical intervention. A database review identified patients aged >35 years with anomalous coronary arteries diagnosed by cardiac catheterization or coronary computed tomography angiography. The outcomes of patients with R-ACAOS-IM were compared with patients with anomalous left circumflex coronary arteries with retroaortic course (LCx-RA) (an anomaly not associated with ischemic events). The primary outcome was all-cause mortality. The study population consisted of 185 patients aged 59 ± 12 years. Clinical characteristics were similar in the R-ACAOS-IM (n = 88) and LCx-RA (n = 97) groups. At a follow-up of 6.6 ± 4.5 years, there was no difference in mortality (hazard ratio 0.64, 95% confidence interval 0.32 to 1.28, p = 0.20) when adjusted for gender, age, and CAD. A subgroup analysis of 88 patients with no obstructive CAD managed nonoperatively found no difference between the LCx and R-ACAOS-IM groups in mortality (hazard ratio 2.45, 95% confidence interval 0.45 to 13.40, p = 0.30). There was no significant difference between the 2 groups in the composite outcome of death, nonfatal myocardial infarction, or survived cardiac arrest. The outcome of adult patients who have anomalous R-ACAOS-IM are similar to patients who have anomalous LCx-RA with a known benign course. In conclusion, these results suggest that most patients who survive this anomaly into adulthood may be managed conservatively without intervention.
Subject(s)
Coronary Artery Disease , Coronary Vessel Anomalies , Sinus of Valsalva , Child , Adolescent , Humans , Adult , Sinus of Valsalva/diagnostic imaging , Sinus of Valsalva/abnormalities , Retrospective Studies , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Coronary Vessel Anomalies/diagnostic imaging , Coronary Vessel Anomalies/complicationsABSTRACT
The current study evaluated whether total cost of care (TCOC) and target price were aligned in Oncology Care Model (OCM) hematologic malignancy episodes and identified factors associated with episodes exceeding target price. Hematologic malignancy episodes from OCM performance period 1-4 reconciliation reports were identified from a large academic medical center. Of the 516 hematologic malignancies episodes included in the analysis, 283 (54.8%) exceeded the target price. Episode characteristics found to be statistically significantly associated with exceeding target price were Medicare Part B drug use and Part D drug use, novel therapy use, home health agency, and >730 days from last chemotherapy. The mean TCOC was $85 374 (± $26 342) for the episodes that exceeded target price while the mean target price was $56 106 (±$16 309). The results found a substantial misalignment between the TCOC and target price for hematologic malignancy episodes, adding to the existing evidence on the lack of adequate adjustment to the OCM target price.
Subject(s)
Hematologic Neoplasms , Medicare , Aged , Humans , United States , Medical Oncology , Hematologic Neoplasms/drug therapyABSTRACT
Community-based breast cancer prevention efforts often focus on women who live in the same neighborhoods, as they tend to have similar demographic characteristics, health behaviors, and environmental exposures; yet little research describes methods of selecting neighborhoods of focus for community-based cancer prevention interventions. Studies frequently use demographics from census data, or single breast cancer outcomes (e.g., mortality, morbidity) in order to choose neighborhoods of focus for breast cancer interventions, which may not be optimal. This study presents a novel method for measuring the burden of breast cancer among neighborhoods that could be used for selecting neighborhoods of focus. In this study, we 1) calculate a metric composed of multiple breast cancer outcomes to describe the burden of breast cancer in census tracts Philadelphia, PA, USA; 2) map the neighborhoods with the greatest breast cancer burden; and 3) compare census tracts with the highest burden of breast cancer to those with demographics sometimes used for geo-based prioritization, i.e., race and income. The results of our study showed that race or income may not be appropriate proxies for neighborhood breast cancer burden; comparing the breast cancer burden with demographics at the census tract level, we found few overlaps with the highest percentage African American or the lowest median incomes. Agencies implementing community-based breast cancer interventions should consider this method to inform the selection of neighborhoods for breast cancer prevention interventions, including education, screening, and treatment.
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Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p < 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Nivolumab/adverse effects , Ipilimumab/adverse effects , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Head , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/radiotherapySubject(s)
Malnutrition , Nutritional Status , Humans , Aged , Geriatric Assessment , Nutrition Assessment , Frail ElderlyABSTRACT
BACKGROUND: Patient participation in clinical trials is influenced by demographic and other individual level characteristics. However, there is less research on the role of geography and neighborhood-level factors on clinical trial participation. This study identifies the demographic, clinical, geographic, and neighborhood predictors of consenting to a clinical trial among cancer patients at a large, urban, NCI-designated cancer center in the Mid-Atlantic region. METHODS: We used demographic and clinical data from patients diagnosed with cancer between 2015 and 2017. We geocoded patient addresses and calculated driving distance to the cancer center. Additionally, we linked patient data to neighborhood-level educational attainment, social capital and cancer prevalence. Finally, we used generalized linear mixed-effects conditional logistic regression to identify individual and neighborhood-level predictors of consenting to a clinical trial. RESULTS: Patients with higher odds of consenting to trials were: Non-Hispanic White, aged 50-69, diagnosed with breast, GI, head/neck, hematologic, or certain solid tumor cancers, those with cancers at regional stage, never/former tobacco users, and those with the highest neighborhood social capital index. Patients who lived further from the cancer center had higher odds of consenting to a trial. With every 1-km increase in residential distance, there was a 4% increase in the odds that patients would consent to a trial. Neither of the additional neighborhood-level variables predicted consenting to a clinical trial. CONCLUSIONS: This study identifies important demographic, patient-level, and geographic factors associated with consenting to cancer clinical trials, and lays the groundwork for future research exploring the role of neighborhood-level factors in clinical trial participation.
Subject(s)
Neoplasms , Humans , Logistic Models , Linear Models , Neoplasms/epidemiology , Neoplasms/therapy , Residence CharacteristicsABSTRACT
Prior work has shown that microbubble-assisted delivery of oxygen improves tumor oxygenation and radiosensitivity, albeit over a limited duration. Lonidamine (LND) has been investigated because of its ability to stimulate glycolysis, lactate production, inhibit mitochondrial respiration, and inhibit oxygen consumption rates in tumors but suffers from poor bioavailability. The goal of this work was to characterize LND-loaded oxygen microbubbles and assess their ability to oxygenate a human head and neck squamous cell carcinoma (HNSCC) tumor model, while also assessing LND biodistribution. In tumors treated with surfactant-shelled microbubbles with oxygen core (SE61O2) and ultrasound, pO2 levels increased to a peak 19.5 ± 9.7 mmHg, 50 s after injection and returning to baseline after 120 s. In comparison, in tumors treated with SE61O2/LND and ultrasound, pO2 levels showed a peak increase of 29.0 ± 8.3 mmHg, which was achieved 70 s after injection returning to baseline after 300 s (p < 0.001). The co-delivery of O2andLNDvia SE61 also showed an improvement of LND biodistribution in both plasma and tumor tissues (p < 0.001). In summary, ultrasound-sensitive microbubbles loaded with O2 and LND provided prolonged oxygenation relative to oxygenated microbubbles alone, as well as provided an ability to locally deliver LND, making them more appropriate for clinical translation.
Subject(s)
Microbubbles , Neoplasms , Humans , Indazoles , Oxygen , Tissue DistributionABSTRACT
PURPOSE: Guidelines for prostate cancer (PCA) germline testing (GT) have expanded, with impact on clinical management and hereditary cancer assessment. African American (AA) men have lower engagement in GT, with concern for widening disparities in genetically informed care. We evaluated the germline spectrum in a cohort of men with PCA enriched for AA men who underwent GT to inform tailored genetic evaluation strategies. METHODS: Participants included AA and White men with PCA tested with a 14-gene PCA panel: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53. Germline analysis was performed per standard clinical testing and variant classification protocols. Data were compared with Fisher's exact, chi-squared, or two sample t-tests, as appropriate. Multivariable analysis was conducted using Akaike's Information Criterion. The significance level was set a priori at .05. RESULTS: The data set included 427 men all tested using the 14-gene PCA panel: AA (n = 237, 56%) and White (n = 190, 44%). Overall, the pathogenic/likely pathogenic (P/LP) variant rate was 8.2%, with AA men having lower rates of P/LP variants then White men (5.91% v 11.05%, respectively; P = .05). Borderline associations with P/LP variant status were observed by race (AA v White; odds ratio = 0.51; P = .07) and age (> 50 v ≤ 50 years; odds ratio = 0.48; P = .06). The P/LP spectrum was narrower in AA men (BRCA2, PALB2, ATM, and BRCA1) than White men (BRCA2, ATM, HOXB13, CHEK2, TP53, and NBN). A significant difference was noted in rates of variants of uncertain significance (VUSs) between AA men and White men overall (25.32% v 16.32%; P = .02) and for carrying multiple VUSs (5.1% v 0.53%, P = .008). CONCLUSION: Germline evaluation in a cohort enriched for AA men highlights the narrower spectrum of germline contribution to PCA with significantly higher rates of multiple VUSs in DNA repair genes. These results underscore the imperative to engage AA men in GT, the need for larger panel testing in AA men, and the necessity to incorporate novel genomic technologies to clarify VUS to discern the germline contribution to PCA. Furthermore, tailored genetic counseling for AA men is important to ensure understanding of VUS and promote equitable genetics care delivery.
Subject(s)
Black or African American , Prostatic Neoplasms , Black or African American/genetics , Genes, BRCA2 , Genetic Testing/methods , Germ Cells/pathology , Humans , Male , Middle Aged , Prostatic Neoplasms/diagnosisABSTRACT
OBJECTIVE: Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear. METHODS: This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values >200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch. RESULTS: In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models. CONCLUSIONS: Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.
Subject(s)
Anti-HIV Agents , Drug Substitution , HIV Infections , Tenofovir , Weight Gain , Adenine/therapeutic use , Adult , Alanine/therapeutic use , Anti-HIV Agents/therapeutic use , Cardiovascular Diseases/epidemiology , Cholesterol/blood , Fumarates/therapeutic use , HIV Infections/drug therapy , Humans , Retrospective Studies , Sustained Virologic Response , Tenofovir/analogs & derivatives , Tenofovir/therapeutic useABSTRACT
The National Lung Screening Trial established the benefits of low-dose computed tomography for lung cancer screening (LCS) to identify lung cancer at earlier stages. In February 2021, the US Preventive Services Task Force (USPSTF) revised the eligibility recommendations to increase the number of high-risk individuals eligible for LCS and, in effect, expand screening eligibility for vulnerable populations. One strategy for facilitating LCS is to implement targeted screening in geographic areas with the greatest need. In Philadelphia, although neighborhood smoking rates have been defined, it is not known which neighborhoods have the greatest number of people eligible for LCS. In this study, the authors estimate eligibility for LCS within Philadelphia neighborhoods using both previous and current USPSTF guidelines. They used the Public Health Management Corporation's Household Health Survey from 2010, 2012, and 2015 to identify the number of people within ever-smoker groups (current every day, current occasional, and former smokers) by neighborhood in Philadelphia. Using the 2015 National Health Interview Survey (NHIS) Cancer Supplement, they identified the percentages within ever-smoker groups that were LCS eligible using the previous and current USPSTF guidelines. Finally, they applied the percentages eligible for the ever-smoker groups from the NHIS to the numbers in these groups within Philadelphia neighborhoods. They found that the number of Philadelphians eligible for LCS increased from 41,946 to 89,231 after the revised USPSTF guidelines. The current USPSTF guidelines increased eligibility for LCS within all Philadelphia neighborhoods, with the greatest increases in the River Wards planning district. Local providers should use these results to prioritize LCS services within neighborhoods with greatest eligibility.
Subject(s)
Early Detection of Cancer , Lung Neoplasms , Early Detection of Cancer/methods , Humans , Lung Neoplasms/diagnosis , Mass Screening , Philadelphia , Tomography, X-Ray Computed/methodsABSTRACT
Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.
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BACKGROUND: Pancreatic cancer (PC) is one of the most aggressive and challenging cancer types to effectively treat, ranking as the fourth-leading cause of cancer death in the United States. We investigated if exposures to angiotensin II receptor blockers (ARBs) or angiotensin I converting enzyme (ACE) inhibitors after PC diagnosis are associated with survival. METHODS: PC patients were identified by ICD-9 diagnosis and procedure codes among the 3.7 million adults living in the Emilia-Romagna Region from their administrative health care database containing patient data on demographics, hospital discharges, all-cause mortality, and outpatient pharmacy prescriptions. Cox modeling estimated covariate-adjusted mortality hazard ratios for time-dependent ARB and ACE inhibitor exposures after PC diagnosis. RESULTS: 8,158 incident PC patients were identified between 2003 and 2011, among whom 20% had pancreas resection surgery, 36% were diagnosed with metastatic disease, and 7,027 (86%) died by December 2012. Compared to otherwise similar patients, those exposed to ARBs after PC diagnosis experienced 20% lower mortality risk (HR=0.80; 95% CI: 0.72, 0.89). Those exposed to ACE inhibitors during the first three years of survival after PC diagnosis experienced 13% lower mortality risk (HR=0.87; 95% CI: 0.80, 0.94) which attenuated after surviving three years (HR=1.14; 95% CI: 0.90, 1.45). CONCLUSIONS: The results of this large population study suggest that exposures to ARBs and ACE inhibitors after PC diagnosis are significantly associated with improved survival. ARBs and ACE inhibitors could be important considerations for treating PC patients, particularly those with the worst prognosis and most limited treatment options. Considering that these common FDA approved drugs are inexpensive to payers and present minimal increased risk of adverse events to patients, there is an urgent need for randomized clinical trials, large simple randomized trials, or pragmatic clinical trials to formally and broadly evaluate the effects of ARBs and ACE inhibitors on survival in PC patients.
Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Pancreatic Neoplasms/mortality , Aged , Aged, 80 and over , Female , Humans , Male , Pancreatic Neoplasms/drug therapy , Proportional Hazards Models , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: One-carbon metabolism genes are linked to several cancers, but the association with prostate cancer (PCa) is less clear. Studies examining the relationship have not accounted for obesity, a risk factor for advanced PCa and altered methylation patterns. We hypothesized that obesity could moderate the association between one-carbon metabolism genes and PCa outcomes. METHODS: We conducted secondary data analyses of the Study of Clinical Outcomes, Risk and Ethnicity. Obesity was included as a primary exposure and modifier (interacting with genetic polymorphisms) in the analytic models. We used logistic regression to determine associations of common one-carbon metabolism genotypes with odds of high stage (T3/T4) and high grade (Gleason score ≥ 7). We used Cox regression to examine associations of genotypes with biochemical recurrence. RESULTS: There were 808 patients (632 White and 176 Black.) Among White men, we observed associations of TCN2_R259P with increased odds of high stage (OR = 0.64, 95% CI = 0.41-1.00), but no significant interactions with obesity. Among Black men, the SCL19A1_61bpdel and CBS_68bpINS variants were associated with high grade (OR = 2.61, 95% CI = 1.39-4.89 and OR = 0.29, 95% CI = 0.09-0.91, respectively.) Both the CBS_68bpINS and MTHFR_E429A variants interacted with obesity in Black men, where the highest risk for biochemical failure and odds of high grade, respectively, occurred among obese patients with variants. CONCLUSIONS: We observed associations of one-carbon metabolism genes with different associations by race. We also observed interactions with obesity related to PCa outcomes in Black men only. Therefore, the involvement of one-carbon metabolism on PCa was dependent upon obesity status for Black men. These novel results could help identify patients that might benefit from effective weight management targeting one-carbon metabolism effects.