Citations

Introduction: There are minimal data to guide antibiotic management of patients undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia. Specifically, management of high-risk patients who are catheter dependent or have positive preoperative urine cultures varies widely. We aimed to evaluate the effect of preoperative antibiotic duration on infectious complications in high-risk patients undergoing HoLEP. Methods: A multi-institutional retrospective review of patients undergoing HoLEP between 2018 and 2023 at five institutions was performed. Patients were defined as high risk if they were catheter-dependent (indwelling urethral catheter, self-catheterization, or suprapubic tube) or had a positive preoperative urine culture. These patients were categorized into long course (>3 days) or short course (≤3 days) of preoperative antibiotics. The primary outcome was 30-day infectious complications defined as a positive urine culture with symptoms. A t -test or Wilcoxon rank-sum test was used for continuous variables and Fisher's exact test was used for categorical variables. Logistic regression analysis was conducted to identify associations with infectious complications. Results: Our cohort included 407 patients, of which 146 (36%) and 261 (64%) were categorized as short course and long course of preoperative antibiotics, respectively. Median preoperative antibiotic duration was 1 day (interquartile range [IQR]: 0, 3 days) and 7 days (IQR: 5, 7 days) in the short and long cohorts, respectively. Thirty-day postoperative infectious complications occurred in 11 (7.6%) patients who received a short course of antibiotics and 5 (1.9%) patients who received a long course of antibiotics (odds ratio 0.24, 95% confidence interval 0.07–0.67; p = 0.009). Variables such as age, positive urine culture, and postoperative antibiotic duration were not significantly associated with postoperative infection after propensity score weighting. Conclusion: In high-risk patients undergoing HoLEP, infectious complications were significantly lower with a long course vs short course of antibiotics. Further prospective trials are needed to identify optimal preoperative antibiotic regimens.

Abstract Clozapine is primarily metabolized via cytochrome P450(CYP)1A2 and to a lesser extent CYP3A4, CYP2C19, and CYP2D6. Metabolic inhibitors of clozapine, such as fluvoxamine and ciprofloxacin, are important to recognize to avoid adverse drug events. Estrogen-containing oral contraceptives (eOCPs) are weaker CYP1A2 and CYP2C19 inhibitors but are associated with a 2-fold increase of clozapine concentrations. The potential for phenoconversion due to a CYP genetic polymorphism can add additional complexities when considering drug interactions. A case report is presented of a suspected interaction between newly initiated clozapine and a prescribed eOCP for which the patient’s pharmacogenomic status was known. A 17-year-old, nonsmoking, White female with a history of schizophrenia was initiated on clozapine 12.5 mg at bedtime with a plan to increase by 25 mg every 4 days in the outpatient setting. The patient was a known rapid CYP1A2 metabolizer without identified sources of CYP1A2 induction and a CYP2C19 rapid metabolizer. Based on pharmacogenomic testing, there was no suspicion for significant gene-drug interactions. Yet, as the patient was prescribed an eOCP, a clozapine concentration was obtained after reaching 150 mg at bedtime. This steady-state clozapine concentration was found to be 560 ng/mL, correlating with worsening sedation and constipation. Given ongoing side effects, clozapine was lowered to 100 mg at bedtime; however, ongoing intolerance ultimately led to clozapine discontinuation. This case highlights the potential interaction between clozapine and eOCP in a CYP1A2 and CYP2C19 rapid metabolizer, leading to clozapine intolerance and discontinuation. The concomitant use of clozapine and eOCPs should be undertaken judiciously.

1604 Background: Diversity in clinical studies is essential to address health disparities, but racial and ethnic minorities are often underrepresented in clinical studies, especially in precision medicine studies using genetic data (1). BASECAMP-1 (NCT04981119) is an ongoing prescreening study to identify patients with unresectable advanced or metastatic solid tumors and tumor-associated HLA-A*02 LOH for the EVEREST-1 and -2 Tmod chimeric antigen receptor T-cell therapy trials. When enrollment began in 2021, eligibility for Part 1 was restricted to patients with germline HLA-A*02:01 based on preclinical data. Additional analysis revealed the blocker in the Tmod construct had activity across HLA-A*02 subtypes (Mock, et al. Mol Ther Oncolytics.2022). Eligibility for Part 1 was then expanded to all HLA-A*02 subtypes, allowing enrollment of more diverse patient populations. HLA-A*02 allele subtypes vary by ethnicity and race; the frequency of HLA-A*02:01 is 96% in non-Hispanic Whites, but ranges from 53% to 73% in other ethnicities and races. The frequency of all other HLA-A*02 allele subtypes (HLA-A*02:XX) is <5% in non-Hispanic Whites but up to 66% in other ethnicities and races (2,3). Methods: Patients eligible for BASECAMP-1 were identified at United States study sites. All patients screened before January 16, 2024, for Part 1 were included for demographic and central lab HLA-A typing. The % increase in eligibility and % of heterozygous HLA-A*02 patients with HLA-A*02:XX were calculated by ethnicity and race. Results: A total of 1124 patients were screened for germline HLA-A*02 typing; 431 patients were HLA-A*02:01 heterozygous, of whom 37 (9%) were Hispanic, 14 (3%) African American (AA), 2 (<1%) American Indian or Alaska Native, 17 (4%) Asian or Pacific Islander (API), and 324 (75%) non-Hispanic White (Table). The eligibility expansion identified 62 patients with HLA-A*02:XX heterozygosity, of whom 6 (10%) were Hispanic, 6 (10%) AA, 19 (31%) API, and 25 (40%) non-Hispanic White. Conclusions: By expanding enrollment to include HLA-A*02:XX, 16% more Hispanic, 43% more AA, and 112% more API patients were identified, improving the diversity in this trial compared with that of initial enrollment. 1. Aldrighetti, et al. JAMA Netw Open 2021. 2. Ellis, et al. Human Immunol. 2000. 3. Gragert, et al. Human Immunol.2013. Clinical trial information: NCT04981119 . [Table: see text]

TPS632 Background: Male breast cancer is a rare disease, and most cases are hormone receptor-positive (HR+). Due to a lack of clinical trials, male breast cancer has historically been treated based on data extrapolated from women. However, there are substantial knowledge gaps in the comparative efficacy, safety, and patient-reported outcomes of endocrine therapies for male breast cancer. While tamoxifen is the current standard of care, additional data are warranted for aromatase inhibitors (AI), gonadal suppression, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This is an open-label, multicenter, randomized, phase II trial designed to evaluate different endocrine therapies in men with HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. A total of 60 men will be enrolled across nine (9) sites within the Translational Breast Cancer Research Consortium (TBCRC). Key eligibility criteria include male sex and stage I, II, or III HR+/HER2- breast cancer before surgical resection of the primary tumor and axillary nodes. Key exclusion criteria include prior anti-cancer therapy for the current breast cancer or any other malignancy within the past 12 months, and inflammatory breast cancer. The trial has two phases. The first phase is a window of opportunity component in which newly diagnosed men are randomized 1:1:1 to either tamoxifen (Arm A), anastrozole (Arm B), or anastrozole plus degarelix (Arm C) given for three weeks. The primary endpoint for the window phase is Ki-67 reduction from the baseline diagnostic biopsy to the research biopsy at the end of the window phase. The second phase consists of neoadjuvant treatment, in which the tamoxifen group is randomized 1:1 to tamoxifen (Arm D) versus tamoxifen plus abemaciclib (Arm E), and the anastrozole alone (Arm B) and anastrozole plus degarelix (Arm C) groups are merged and then randomized 1:1 to anastrozole plus degarelix (Arm F) versus anastrozole plus degarelix plus abemaciclib (Arm G). The duration of the neoadjuvant phase is four (4) months, and the primary endpoint of this phase is residual cancer burden (RCB) index at time of surgery. The trial is powered for the RCB endpoint in a 2 x 2 factorial design to detect a 0.6 unit decrease in RCB index with 80% power and alpha=10%. For the Ki-67 endpoint, we assume an approximately 50% reduction in Arms A and B; Arm C will be of interest if it leads to ≥80% reduction in Ki-67. Secondary endpoints include: estradiol and testosterone levels at baseline, end of window, and during neoadjuvant phase; preoperative endocrine prognostic index (PEPI) score at surgery; adverse events; and patient-reported outcomes (including quality of life). Tumor tissue will be collected for correlative analyses. The study opened to enrollment at Dana-Farber in October 2023, and additional sites will open in 2024. Clinical trial information: NCT05501704 .

This cross-sectional study evaluates the prevalence of and characteristics associated with discontinuation of cancer treatment among patients who received a diagnosis of COVID-19 during their treatment planning.

Purpose: While it is well-known that elite males are faster than elite females in all Olympic-length swimming events, less is known about the age of the divergence in swimming performance between the sexes. Thus, this observational study compared swimming performance of elite male and female youths. Methods: We collected the all-time best 100 U.S. freestyle swimming performance times of boys and girls aged 5 to 18 years for six freestyle swimming events from 50m to 1500m. We compared data using univariate ANOVAs and Chi-squared tests. Results: Swimming performance improved with increasing age for both boys and girls (p<0.001) until a plateau— which began at a younger age for girls (15 years) than boys (17 years; sex × age; p<0.001). Before age 8, there was no sex difference in swimming performance (p>0.05). Beginning at age 9 however, boys swimming performance was faster than girls (1.0% to 1.3% depending on distance), and this sex difference in performance increased in magnitude until 18 years (p<0.001; 6.6% to 11.0% depending on distance). While boys represent 50% of the top 100 age-group performances at ages 5 and 6, boys represent an increasingly larger proportion of top performances across years of age including nearly 100% of all top 100 age-group performances beginning at age 15—except for one notable female swimmer in the 1500m Conclusion: Among elite youth swimmers, boys have increasingly faster performances than girls beginning at age 9 years, with minimal sex differences in swimming performance before 9 years. Additionally, boys represent an increasingly larger proportion of the top 100 age-group performances of all-time. No funding. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ImportanceRacially and ethnically minoritized US adults were disproportionately impacted by the COVID-19 pandemic and experience poorer cancer outcomes, including inequities in cancer treatment delivery.ObjectiveTo evaluate racial and ethnic disparities in cancer treatment delays and discontinuations (TDDs) among patients with cancer and SARS-CoV-2 during different waves of the COVID-19 pandemic in the United States.Design, Setting, and ParticipantsThis cross-sectional study used data from the American Society of Clinical Oncology Survey on COVID-19 in Oncology Registry (data collected from April 2020 to September 2022), including patients with cancer also diagnosed with SARS-CoV-2 during their care at 69 US practices. Racial and ethnic differences were examined during 5 different waves of the COVID-19 pandemic in the United States based on case surge (before July 2020, July to November 2020, December 2020 to March 2021, April 2021 to February 2022, and March to September 2022).ExposuresRace and ethnicity.Main Outcomes and MeasuresTDD was defined as any cancer treatment postponed more than 2 weeks or cancelled with no plans to reschedule. To evaluate TDD associations with race and ethnicity, adjusted prevalence ratios (aPRs) were estimated using multivariable Poisson regression, accounting for nonindependence of patients within clinics, adjusting for age, sex, body mass index, comorbidities, cancer type, cancer extent, and SARS-CoV-2 severity (severe defined as death, hospitalization, intensive care unit admission, or mechanical ventilation).ResultsA total of 4054 patients with cancer and SARS-CoV-2 were included (143 [3.5%] American Indian or Alaska Native, 176 [4.3%] Asian, 517 [12.8%] Black or African American, 469 [11.6%] Hispanic or Latinx, and 2747 [67.8%] White; 2403 [59.3%] female; 1419 [35.1%] aged 50-64 years; 1928 [47.7%] aged ≥65 years). The analysis focused on patients scheduled (at SARS-CoV-2 diagnosis) to receive drug-based therapy (3682 [90.8%]), radiation therapy (382 [9.4%]), surgery (218 [5.4%]), or transplant (30 [0.7%]), of whom 1853 (45.7%) experienced TDD. Throughout the pandemic, differences in racial and ethnic inequities based on case surge with overall TDD decreased over time. In multivariable analyses, non-Hispanic Black (third wave: aPR, 1.56; 95% CI, 1.31-1.85) and Hispanic or Latinx (third wave: aPR, 1.35; 95% CI, 1.13-1.62) patients with cancer were more likely to experience TDD compared with non-Hispanic White patients during the first year of the pandemic. By 2022, non-Hispanic Asian patients (aPR, 1.51; 95% CI, 1.08-2.12) were more likely to experience TDD compared with non-Hispanic White patients, and non-Hispanic American Indian or Alaska Native patients were less likely (aPR, 0.37; 95% CI, 0.16-0.89).Conclusions and RelevanceIn this cross-sectional study of patients with cancer and SARS-CoV-2, racial and ethnic inequities existed in TDD throughout the pandemic; however, the disproportionate burden among racially and ethnically minoritized patients with cancer varied across SARS-CoV-2 waves. These inequities may lead to downstream adverse impacts on cancer mortality among minoritized adults in the United States.