Publications by authors named "Ian Hirsch"

Importance: Large language models (LLMs) recently developed an unprecedented ability to answer questions. Studies of LLMs from other fields may not generalize to medical oncology, a high-stakes clinical setting requiring rapid integration of new information.

Objective: To evaluate the accuracy and safety of LLM answers on medical oncology examination questions.

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Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

Design, Setting, And Participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax.

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Background: An improved understanding of how severe asthma heterogeneity affects response could inform treatment decisions.

Objectives: Characterize heterogeneity and benralizumab responsiveness in patients grouped by predefined Severe Asthma Research Program clusters using a multivariate approach.

Methods: In post-hoc analyses of the randomized, double-blind, placebo-controlled phase III SIROCCO (NCT01928771) and CALIMA (NCT01914757) studies, patients with severe asthma who received benralizumab or placebo were assigned to clusters using an established discriminant function to analyze 11 clinical characteristics simultaneously.

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While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S.

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Background: Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions.

Methods: A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials.

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Background: CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma.

Methods: This analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo.

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Article Synopsis
  • Radiation-induced sarcomas (RIS) are rare and aggressive tumors that can complicate treatment decisions due to their unique characteristics and origins in previously irradiated tissues.
  • A retrospective study using the CanSaRCC database analyzed RIS cases from 1996 to 2021, looking specifically at patient demographics, treatment, and outcomes across different sarcoma types.
  • Among the 107 identified RIS tumors, breast angiosarcoma (BAS) was most common and associated with specific clinical trends, including a younger age for osteosarcoma patients and varying time intervals since initial cancer treatment.
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Article Synopsis
  • Study explores the protective effects of previous SARS-CoV-2 infection and hybrid immunity (infection plus vaccination) against COVID-19, using data from various vaccine trials.
  • Participants were grouped based on their previous infection status and whether they received a vaccine, with a main focus on confirmed COVID-19 cases post-treatment.
  • Results indicated that individuals with previous infections had a significantly lower risk of contracting COVID-19, and hybrid immunity generally offered better protection than vaccination alone, emphasizing the effectiveness of both natural infection and vaccination in preventing severe disease.
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Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions that would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022.

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Immune checkpoint inhibitors have revolutionized cancer treatment. They can induce cutaneous immune-related adverse events. One patient with immune-related eczema and two with immune-related bullous pemphigoid were successfully treated with dupilumab.

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Importance: Current data identifying COVID-19 risk factors lack standardized outcomes and insufficiently control for confounders.

Objective: To identify risk factors associated with COVID-19, severe COVID-19, and SARS-CoV-2 infection.

Design, Setting, And Participants: This secondary cross-protocol analysis included 4 multicenter, international, randomized, blinded, placebo-controlled, COVID-19 vaccine efficacy trials with harmonized protocols established by the COVID-19 Prevention Network.

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In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19).

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Background: The stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood.

Objective: This post hoc, longitudinal, pooled analysis of placebo-arm patients from 2 phase 3 studies evaluated the clinical implications of BEC stability and variability in moderate-to-severe asthma.

Methods: This analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β-agonists; 2:1 patients with BECs of 300 cells/μL or higher and less than 300 cells/μL were enrolled.

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Background: Non-cytotoxic therapy has changed the treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients. With unique mechanisms of action, these agents have decidedly improved survival and have demonstrated an improved toxicity profile. However, the real-life experience of the patient, which is commonly assessed by health-related quality of life (HRQoL) measurement, is not clearly established with this new generation of lung cancer treatments.

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Background: Benralizumab is an IL-5 receptor alpha-directed cytolytic mAb that depletes eosinophils, reducing exacerbations and oral corticosteroid (OCS) use, and improves asthma control for patients with severe eosinophilic asthma (SEA). Data on response in patients previously treated with other biologic therapies are limited.

Objective: To describe real-world clinical outcomes with benralizumab for patients with and without prior biologic use for uncontrolled SEA.

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The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2.

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Background: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

Methods: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

Results: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants).

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Background: Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma.

Methods: Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations.

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Introduction: Breast cancer is the tumor with highest incidence in women worldwide and adjuvant treatment is extremely important to achieve disease control. Given the relevance of systematic reviews, their rigor should be warranted to avoid biased conclusions. Our objective was to investigate the methodological quality of meta-analysis of early breast cancer adjuvant treatment.

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Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects.

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Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses.

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Background: Several candidate vaccines to prevent COVID-19 disease have entered large-scale phase 3 placebo-controlled randomized clinical trials and some have demonstrated substantial short-term efficacy. Efficacious vaccines should, at some point, be offered to placebo participants, which will occur before long-term efficacy and safety are known.

Methods: Following vaccination of the placebo group, we show that placebo-controlled vaccine efficacy can be derived by assuming the benefit of vaccination over time has the same profile for the original vaccine recipients and the placebo crossovers.

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Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa.

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Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy of these vaccines, a general set of clinical endpoints is proposed, along with considerations to guide the selection of the primary endpoints on the basis of clinical and statistical reasoning. The plausibility that vaccine protection against symptomatic COVID-19 could be accompanied by a shift toward more SARS-CoV-2 infections that are asymptomatic is highlighted, as well as the potential implications of such a shift.

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