Citations

ABSTRACT Background ASP‐1929 photoimmunotherapy—cetuximab conjugated to IRDye 700DX and red light (690 nm) for localized drug activation—results in rapid, selective cell killing. Methods This phase Ib/II open‐label study evaluated ASP‐1929 photoimmunotherapy plus pembrolizumab in patients with recurrent/metastatic HNSCC (≥ 1 accessible lesion, PD‐L1 combined positive score ≥ 1, ineligible for standard locoregional therapy). Primary objectives were safety/tolerability and objective response rate (ORR). Secondary objectives included overall survival (OS) and progression‐free survival (PFS). Results Eighteen patients (median age 63 years, 74% male) comprised the photoimmunotherapy‐evaluable population. The confirmed ORR was 27.8% (95% CI 9.7–53.5); four of five responders had complete responses (95% CI, 6.4–47.6). Median OS was 25.6 months (95% CI, 14.6–not evaluable); median PFS was 2.9 months (95% CI, 1.4–14.6). The most common serious adverse reactions were dysphagia and tongue edema (each n = 2; 10.5%). Conclusions ASP‐1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

AbstractElectronic patient-reported outcome measures (ePROMs) can improve care for people with cancer, but effectiveness hinges on well-supported integration in clinical settings.We evaluated clinician use of specific clinical decision support (CDS) tools in the electronic health record (EHR) designed to facilitate timely, clinically appropriate responses to ePROM scores for six symptoms commonly experienced by cancer patients.The parent pragmatic trial, which took place at Mayo Clinic (Rochester, Minnesota, United States) and its affiliated community health care system between March 2019 and January 2023, evaluated the population-level effectiveness and implementation of an ePROM surveillance and EHR-facilitated collaborative care symptom management intervention. The present evaluation used a case study approach with four data sources: (1) clinician interactions with CDS tools abstracted from the EHR; (2) clinician notes identified with an institution-specific textual search tool; (3) qualitative interviews and group discussions with care teams; and (4) administrative records reviewed to identify training and outreach to care teams.EHR metrics showed very low adoption of CDS tools including alerts and symptom-specific order sets, despite educational outreach and information technology support provided to clinical care teams. Qualitative findings revealed that CDS use was not easy to integrate into busy clinical workflows and highlighted clinician perceptions that the collaborative care intervention provided additional patient support that reduced clinicians' need to utilize CDS tools. They also highlight the importance of contextual factors, including institutional priorities and EHR changes.This pragmatic clinical trial case study found limited adoption of EHR CDS tools that had been developed to increase clinicians' awareness of and responses to ePROM data. Findings suggest the need to align clinician and organizational implementation strategies, simplify CDS tools to fit practice expectations, and identify and address contextual factors that could undercut strategies like education and peer support. This may be especially important for teams who aim to iteratively evaluate and refine CDS and implementation strategies for multicomponent interventions or introduce new strategies that are responsive to barriers while maintaining scalability.

ABSTRACT Human papillomavirus (HPV) is comprised of >200 genotypes and has an ~8 kb, circular, double-stranded DNA genome. Transmission of HPV occurs through skin-to-skin contact and infection of squamous epithelial cells of cutaneous and mucosal surfaces. HPV genotypes are categorized as low- or high-risk (hrHPV) based on oncogenic potential. There are approximately 14 types of hrHPV that can cause several types of cancer, including HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC). Detection of HPV(+)OPSCC is traditionally accomplished using p16 immunohistochemistry (IHC) and HPV-specific testing, either DNA or RNA in situ hybridization (ISH) staining or DNA-based PCR of suspected tumor biopsy tissue. More recently, platelet-poor plasma (PPP) samples from patients with HPV(+)OPSCC have proven useful for detection and quantitation of fragments of HPV circulating tumor DNA (ctDNA). ctDNA has been shown to be useful in determining treatment response and monitoring for disease recurrence. In this study, a novel droplet digital PCR assay (ddPCR) was developed and validated for the detection and quantitation of ctDNA from 5 hrHPV genotypes in PPP. Analytical sensitivity ranged from 7.71 to 19.45 fragments of HPV ctDNA per milliliter of PPP across five hrHPV genotypes. In patients with confirmed primary or recurrent HPV(+)OPSCC or HPV(-)OPSCC, testing of corresponding PPP samples ( n = 32) by ddPCR demonstrated 90.63% (29/32) overall agreement with p16/HPV-ISH biopsy results. Compared with reference ddPCR assays performed at outside laboratories, our ddPCR assay yielded 90% (9/10) overall agreement. This assay may provide clinicians with a tool for monitoring HPV ctDNA prior to, during, and after treatment of an HPV-associated cancer. IMPORTANCE At least 14 genotypes of human papillomavirus (HPV) have been identified to have high oncogenic potential. While molecular diagnostic testing for HPV is widely available for liquid cytologic cervical samples, testing is limited for other sample types, including liquid biopsy samples, such as platelet-poor plasma (PPP). With the rising incidence of HPV-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC), laboratory testing is an essential part of patient diagnosis, management, and surveillance. Here, we summarize the development and analytical performance validation of a multiplexed, droplet digital PCR (ddPCR) assay for the detection and quantitation of HPV circulating tumor DNA (ctDNA) in PPP. This assay may provide clinicians with a tool to address minimal residual disease for patients with an HPV-associated cancer.

This cross-sectional study analyzes patient-reported outcome findings from the Enhanced, Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) trial to investigate level of symptom burden in adolescents and young adults with cancer.

Interaction between breast milk antibodies and gut microbes shape immune responses during weaning

ABSTRACT Background The association between transjugular intrahepatic portosystemic shunt TIPS and waitlist outcomes in simultaneous liver‐kidney (SLK) transplant recipients remains unclear. Methods Between 2003 and 2023, we examined the scientific registry of transplant recipients. All adult candidates with overlapping waiting lists for liver and kidney transplants ( N = 15 087) were analyzed (entire cohort). Candidates without TIPS ( n = 13 980) and with ( n = 1107) were followed through November 30, 2023, and the following outcomes were analyzed: death, SLK transplant, liver‐ or kidney‐alone transplant, or removal from the list. The Aalen–Johansen method was used to calculate the cumulative incidence rates of the outcomes, where the outcomes were considered competing risks. Mixed effects Cox proportional hazard models were used to compare the outcomes by TIPS status. We separately analyzed dialysis‐dependent candidates ( n = 10 370). Results In the entire cohort, the 1‐year cumulative incidence of death in those without TIPS was higher than in those with (12.5% vs. 9%). In the dialysis‐dependent cohort, the 1‐year death incidence was 13.3% versus 8.8% in those without TIPS and those with, respectively. In the multivariable Cox proportional hazard models, TIPS was associated with a 29% lower mortality risk in the entire cohort (HR = 0.71, 95% CI: 0.60–0.84, p < 0.001) and a 33% lower risk of mortality in the dialysis‐dependent cohort. The likelihood of receiving SLK was lower for recipients with TIPS in the univariable analysis. However, this association was attenuated after adjustment. The causes of removal were similar irrespective of TIPS status in both cohorts. Conclusion In this large cohort of SLK candidates, those with TIPS had a better waitlist survival, irrespective of their dialysis requirements before transplantation. Prospective studies are needed to validate these findings.

Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. Objective To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. Design, Setting, and Participants This retrospective cohort study of adults (aged ≥18 years) with T2D and a recent hemoglobin A 1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. Exposures At least 2 prescriptions of a GLP-1 RA given 6 months apart. Main Outcomes and Measures Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. Results After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). Conclusions and Relevance In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D.

Abstract Background Endocrine therapy has been the mainstay treatment for metastatic hormone receptor-positive / HER2-negative (HR+/HER2-) breast cancer. Given that cell cycle dysregulation and consequent uncontrolled cellular proliferation is a key mechanism behind cancer growth, agents targeting this pathway have been of major therapeutic interest.[1] The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors palbociclib, ribociclib, and abemaciclib have shown a synergistic effect in combination with endocrine therapy.[2-3] Despite favorable results, post-approval studies have revealed potential concerns for cardiotoxicity. [4] Given this, we sought to characterize the incidence and outcomes of atrial arrhythmia among metastatic HR+/HER2- breast cancer patients who were treated with CDK 4/6 inhibitors at our institution. Purpose To investigate the incidence and risk factors of atrial arrhythmia among hormone receptor-positive/HER2-negative breast cancer patients treated with CDK4/6 inhibitors at our institution. Methods A retrospective cohort study was conducted among 2754 patients ≥18 years of age who received treatment with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) for an established diagnosis of hormone receptor-positive, HER-2 negative breast cancer between 2015-2024. Patients with new onset atrial fibrillation and/or flutter were identified through chart review. The cumulative incidence of new-onset atrial arrhythmia was estimated using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of atrial arrhythmia. Results A total of 2754 patients was included in the study; 97.3% were female and mean age was 61 years (13). Among these, 101 (3.6%) had a prior history of atrial arrhythmia. The 1-year and 5-year cumulative incidence of new-onset AA were 1.1% and 2.8% respectively (Figure 1). When stratified by specific CDK4/6 inhibitor agents, there was no statistically significant difference. On univariable analysis, age at treatment, hypertension, coronary artery disease, and peripheral vascular disease were associated with new-onset atrial arrhythmia. However, following multivariable adjustment, only age at treatment was statistically significant. Conclusions New-onset atrial arrhythmias may occur during or after CDK4/6 inhibitor use. Older patients appeared to have a higher risk. There were no clear differences in atrial arrhythmia risk between the three CDK4/6 inhibitors.