Publications by authors named "Alex Bryant"

Background: Black patients were severely under-represented in the clinical trials that led to the approval of immune checkpoint inhibitors (ICIs) for all cancers. The aim of this study was to characterise the effectiveness and safety of ICIs in Black patients.

Methods: We did a retrospective cohort study of patients in the US Veterans Health Administration (VHA) system's Corporate Data Warehouse containing electronic medical records for all patients who self-identified as non-Hispanic Black or African American (referred to as Black) or non-Hispanic White (referred to as White) and received PD-1, PD-L1, CTLA-4, or LAG-3 inhibitors between Jan 1, 2010, and Dec 31, 2023.

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Background: The cumulative, health system-wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real-world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system-wide survival impact of ICIs.

Methods: We identified all patients receiving PD-1/PD-L1 or CTLA-4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non-ICI systemic therapy in the years before ICI approval (historical control).

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End-stage liver disease is marked by portal hypertension, systemic elevations in ammonia, and development of hepatocellular carcinoma (HCC). While these clinical consequences of cirrhosis are well described, it remains poorly understood whether hepatic insufficiency and the accompanying elevations in ammonia contribute to HCC carcinogenesis. Using preclinical models, we discovered that ammonia entered the cell through the transporter SLC4A11 and served as a nitrogen source for amino acid and nucleotide biosynthesis.

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Article Synopsis
  • New technologies in radiation oncology can create health care disparities, particularly affecting vulnerable patient populations, necessitating the assessment of these disparities for both existing and new technologies.* -
  • A health disparity risk assessment metric was developed, allowing clinics to determine the potential disparities among patient populations and providing guidelines for addressing these disparities in technology use.* -
  • This metric calculates a disparity risk priority number based on patient impact, the quality of radiation plans, and clinical reliance on technology, enabling clinics to prioritize interventions to enhance equitable care.*
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Purpose: Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men.

Materials And Methods: We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer.

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Article Synopsis
  • Real world evidence is essential for understanding how new cancer treatments spread, monitoring patient outcomes, and identifying unexpected side effects, but collecting this data efficiently can be difficult and costly.
  • The review discusses how artificial intelligence (AI) is being utilized in oncology to analyze large amounts of data related to patients and tumors, offering new biological insights and better risk predictions by integrating various types of datasets.
  • While AI shows promising advancements in oncology, further improvements in computational methods, data applicability, clarity, and validation are necessary for its effective integration into everyday clinical practice and monitoring of cancer therapies.
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Background: Despite randomized trials demonstrating a mortality benefit to low-dose computed tomography screening to detect lung cancer, uptake of lung cancer screening (LCS) has been slow, and the benefits of screening remain unclear in clinical practice.

Methods: This study aimed to assess the impact of screening among patients in the Veterans Health Administration (VA) health care system diagnosed with lung cancer between 2011 and 2018. Lung cancer stage at diagnosis, lung cancer-specific survival, and overall survival between patients with cancer who did and did not receive screening before diagnosis were evaluated.

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Background: Health care is a major source of greenhouse gas emissions, leading to climate change and public health harms. Changes are needed to improve the environmental sustainability of health-care practices, but such changes should not sacrifice patient outcomes or financial sustainability. Alternative dosing strategies that reduce the frequency with which specialty drugs are administered, without sacrificing patient outcomes, are an attractive possibility for improving environmental sustainability.

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Background: Adaptive treatment strategies that can dynamically react to individual cancer progression can provide effective personalized care. Longitudinal multi-omics information, paired with an artificially intelligent clinical decision support system (AI-CDSS) can assist clinicians in determining optimal therapeutic options and treatment adaptations. However, AI-CDSS is not perfectly accurate, as such, clinicians' over/under reliance on AI may lead to unintended consequences, ultimately failing to develop optimal strategies.

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Introduction: Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States.

Materials And Methods: Data from the Veterans Affairs Central Cancer Registry were analyzed for temporal survival trends using Kaplan-Meier estimates and linear regression.

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Importance: The adrenal androgen-metabolizing 3β-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3β-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer.

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Natural language processing (NLP) tools can automate the identification of cancer patients eligible for specific pathways. We developed and validated a cancer agnostic, rules-based NLP framework to extract the dimensions and measurements of several concepts from pathology and radiology reports. This framework was then efficiently and cost-effectively deployed to identify patients eligible for breast, lung, and prostate cancers clinical pathways.

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Article Synopsis
  • - This study analyzed the effectiveness of a genetic risk score (PHS290) in predicting prostate cancer diagnoses during initial biopsies among 36,717 male veterans, including 10,297 of African ancestry.
  • - Higher genetic risk correlated with increased rates of positive biopsies, with low-risk men having a 34% detection rate compared to 58% for high-risk men (P < .001).
  • - Although higher genetic risk significantly increased detection rates for both African and European ancestry groups, it was notably stronger for European men (odds ratio of 3.89 vs. 2.18 for African ancestry), indicating a need for more equitable genetic risk assessments across different ancestry groups.
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Background: Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level.

Methods: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans.

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Purpose: Adjuvant durvalumab after definitive chemoradiotherapy (CRT) for unresectable stage III non-small cell lung cancer (NSCLC) is well-tolerated in clinical trials. However, pneumonitis rates outside of clinical trials remain poorly defined with CRT followed by durvalumab. We aimed to describe the influence of durvalumab on pneumonitis rates among a large cohort of patients with stage III NSCLC.

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Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at "one-size-fits-all" flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending.

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Purpose: National guidelines on limited-stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy in 30 fractions delivered twice daily; however, use of this regimen is uncommon compared with once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily radiation therapy (RT) regimens.

Methods And Materials: Demographic, clinical, and treatment data along with physician-assessed toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the Michigan Radiation Oncology Quality Consortium between 2012 and 2021 for patients with LS-SCLC.

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Purpose: Cannabis use rates are increasing in the United States. Patients with cancer use cannabis for many reasons, even without high-quality supporting data. This study sought to characterize cannabis use among patients seen in radiation oncology in a state that has legalized adult nonmedical use cannabis and to identify key cannabis-related educational topics.

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Importance: There is controversy about the benefit of prostate-specific antigen (PSA) screening. Prostate-specific antigen screening rates have decreased since 2008 in the US, and the incidence of metastatic prostate cancer has increased. However, there is no direct epidemiologic evidence of a correlation between population PSA screening rates and subsequent metastatic prostate cancer rates.

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The COVID-19 pandemic disrupted prostate-specific antigen (PSA) screening and prostate biopsy procedures. We sought to determine whether delayed screening and diagnostic workup of prostate cancer (PCa) was associated with increased subsequent rates of incident PCa and advanced PCa and whether the rates differed by race. We analyzed data from the Veterans Health Administration to assess the changes in the rates of PSA screening, prostate biopsy procedure, incident PCa, PCa with high-grade Gleason score, and incident metastatic prostate cancer (mPCa) before and after January 2020.

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Background: One year of adjuvant durvalumab following concurrent chemoradiotherapy significantly improves progression-free survival (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the optimal length of adjuvant therapy has not been determined.

Methods: We identified patients with stage III NSCLC treated with definitive chemoradiation and adjuvant durvalumab from November 2017 to April 2021 from the United States Veterans Affairs system.

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Objective: To analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy.

Subjects And Methods: We identified 12 784 patients with intermediate- or high-risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60-69, and ≥70 years old).

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Purpose: It is unclear whether programmed death ligand 1 (PD-L1) expression is prognostic or predictive of immunotherapy benefit among patients with stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation and adjuvant durvalumab.

Methods And Materials: We determined pretreatment tumor PD-L1 expression for 312 patients with stage III NSCLC treated with definitive chemoradiation and at least 1 dose of adjuvant durvalumab between November 2017 and April 2021 across the national Veterans Health Administration. Progression-free survival (PFS) and overall survival (OS) in PD-L1 expression subgroups (<1%, 1%-49%, and 50%-100%) were compared with 994 patients with stage III NSCLC treated without adjuvant durvalumab from 2015 to 2016.

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Objective: To develop and validate an accurate, usable prediction model for other-cause mortality (OCM) in patients with prostate cancer diagnosed in the United States.

Materials And Methods: Model training was performed using the National Health and Nutrition Examination Survey 1999-2010 including men aged >40 years with follow-up to the year 2014. The model was validated in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial prostate cancer cohort, which enrolled patients between 1993 and 2001 with follow-up to the year 2015.

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