Genesis Research Institute

Comprehensive biomarker testing is mandatory for advanced non-small cell lung cancer (NSCLC). Pleural effusion cell blocks are a minimally invasive alternative to biopsy. The AmoyDx pan lung cancer (PLC) polymerase chain reaction panel is a sensitive multiplex assay; however, its performance using pleural cell-block specimens with low tumor-cell content remains largely unexplored. We conducted a retrospective study of 30 patients with advanced NSCLC and having known driver mutations, whose pleural effusion cell blocks were tested using the AmoyDx PLC panel at Kanagawa Cancer Center between 2021 and 2023. Tumor content was quantified using thyroid transcription factor 1 immunohistochemistry. DNA and RNA quality were assessed, and the panel results were compared with those of other molecular assays. The AmoyDx PLC panel achieved a detection success rate of 96.7% (29/30), with a sole discordant case owing to the absence of malignant cells. The concordance in confirmed malignant cases was 100%. Notably, the panel detected target mutations in specimens with tumor contents well below the recommended threshold. High detection performance was observed even when the nucleic acid concentrations were suboptimal or the purity levels were outside the reference range. The median tumor content was 8.5% (range, 0.2%-88.2%), with 74% samples below the 20% threshold. Pleural effusion cell blocks are a practical and reliable alternative for molecular testing of advanced NSCLC when biopsy is not feasible. The high sensitivity of the AmoyDx PLC panel even for specimens with low tumor cell content underscores its potential clinical utility.

Abstract Background Targeted therapies have transformed treatment for HR+/HER2- metastatic breast cancer (mBC), but optimal use depends on timely biomarker testing and matched therapy selection. This study evaluated national trends in PIK3CA, PTEN, AKT1 and ESR1 biomarker testing and treatment patterns among U.S. patients (pts) in community oncology clinics and examined factors associated with timely biomarker testing. Methods We conducted a retrospective cohort study of adult pts (≥18 years) with HR+/HER2- mBC treated between 01/01/2018 and 01/31/2025, using de-identified, electronic health record-derived data from the United States Flatiron Health Network. Eligible pts received at least one line of therapy at U.S. community oncology practices. Biomarker testing and treatment patterns across the first three lines of therapy (1L-3L) were analyzed descriptively. Logistic regression model evaluated associations between timely testing and baseline demographic, socioeconomic (SES), and clinical characteristics. Timely testing was defined as completing biomarker testing with results available before initiating a line of therapy for which an approved targeted treatment was available. Results Among 6,197 eligible pts who received 1L therapy, 3,550 progressed to 2L and 2,045 to 3L during the study period. Biomarker testing rates increased over time prior to 1L (from 4% in 2018 to 35% in 2024), 2L (from 9% to 69%), and 3L (from 13% to 83%). CDK4/6 inhibitors were the predominant 1L treatment regardless of biomarker status. In 2L and 3L, treatment patterns became more fragmented. Among pts with known PIK3CA mutations, the use of targeted approved therapies was 32% in 2L and 36% in 3L in 2019, compared to 27% and 29% in 2024. Among pts with ESR1+, elacestrant use rose from 22% in 2023 to 29% in 2024 in 2L and remained steady at 26-27% in 3L. In AKT1/PTEN+ pts, capivasertib use was 6% in 2L and 11% in 3L in 2024. Among pts with no test, or with negative or inconclusive biomarker results, 1% in 1L, 9% in 2L and 17% in 3L received Antibody Drug Conjugates in 2024. Treatment choices for dual-mutant (ESR1+ with either PIK3CA, AKT1 or PTEN) pts remained highly variable, with no dominant regimen: 27% received targeted therapies in 2L versus 34% in 3L. Pts were less likely to receive timely biomarker testing if they were older, lived in lower-SES areas, were treated at smaller practices, or had a worse ECOG score. However, timely testing became more common in more recent years. Conclusions Despite the availability of targeted therapies, major gaps persist in both biomarker testing and the uptake of these treatments. In 2024, nearly one-third of pts remained untested before 2L, and only 35% were tested prior to initiating 1L, limiting timely access to newly approved options. Even when actionable mutations were identified, over two-thirds of eligible pts did not receive matched therapies. Timely testing was less common in smaller practices and lower-SES settings, highlighting systemic barriers to precision oncology. To close these gaps, coordinated, equity-focused strategies are needed to improve timely testing and ensure appropriate use of targeted treatments across all pts populations. Study Number: SL46196 and PL-03044. Financial Statement: This study was sponsored by Genentech, Inc., a member of the Roche Group. Citation Format: I. M. Abbass, D. Lebovitch, N. Jain, T. Stricker, S. Nunnery, A. Pregenzer, E. Behan, R. Wang, L. Chen, P. Dhillon, Y. Liu, T. Szado, E. Yu, S. Ogale. Trends and Barriers in Biomarker Testing and Treatment Patterns in HR+/HER2- Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-12-27.

Abstract Background: Patients (pts) with ER+/HER2- MBC often develop ESR1m during or after 1L treatment with ET with or without a CDK4/6i. Reported ESR1m prevalence rates vary, ranging from 20% to 50% after ≥1 line of therapy in the metastatic setting. Here, we explore the real-world prevalence of ESR1m and co-occurring mutations after 1L ET and/or CDK4/6i among pts with MBC in the GuardantINFORM database. Methods: This was a retrospective cohort study of adults in the United States with ER+/HER2- MBC and a Guardant360 comprehensive genomic profiling blood test of cancer-related gene mutations in circulating tumor DNA (ctDNA) between Jan 1, 2014 and Aug 31, 2024. Eligible pts had received any of the following 1L treatments within 6 months of diagnosis of metastatic disease: ET monotherapy (aromatase inhibitor [AI], selective ER modulator [SERM], or selective ER degrader [SERD]), CDK4/6i monotherapy, or ET (AI/SERM and/or SERD) + CDK4/6i combination therapy. Pts must have subsequently discontinued 1L therapy and received second-line (2L) treatment with follow-up >3 months. Pts were considered ESR1 evaluable if they had an ESR1 test ≤90 days before initiating 2L therapy (to rule out false negatives) or had a positive ESR1m result at any time before starting 2L therapy. ESR1m positivity was defined as missense mutations in codons 310-547. The proportion of ESR1-evaluable pts who were ESR1m positive was stratified by the type and duration of 1L treatment. The incidence of co-occurring AKT1 E17K, PIK3CA, PTEN, CCND1, ERBB2, FGFR1, KRAS, MYC, NF1, and RB1 mutations was analyzed. Results: Of 8335 adults with MBC treated with 1L ET and/or a CDK4/6i who had a Guardant 360 test, 4790 went on to receive 2L treatment with sufficient follow-up, and 1511 were ESR1 evaluable. Of these, 686 pts (45%) were ESR1m-positive, with the highest rates of ESR1m positivity among pts who received 1L SERD monotherapy or SERD + AI/SERM, and those who received 1L treatment for 12 to <24 months (Table). Among pts with ESR1m, 68% (466/686) had ≥1 other co-occurring mutation at start of 2L therapy, most commonly in genes involved in the PI3K/AKT signaling pathway (AKT1 E17K, PIK3CA, or PTEN; 50% [341/686]). Conclusions: In this real-world analysis of the GuardantINFORM database, 45% of pts with ER+/HER2- MBC were ESR1m-positive following 1L treatment with ET and/or CDK4/6i. The ESR1m positivity rate remained >40% in most subgroups analyzed according to 1L therapy type and 1L treatment duration. Other mutations co-occurred in >65% of pts with ESR1m. Citation Format: D. Chandiwana, D. Benjumea, K. Greco, C. Grace Rose, S. Stergiopoulos, J. Liao, M. Edwards. Real-world prevalence of ESR1 mutations (ESR1m) among patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) after first-line (1L) treatment with endocrine therapy (ET) and/or a cyclin dependent kinase 4/6 inhibitor (CDK4/6i) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-09.

Abstract Background Group B Streptococcus (GBS) is a leading cause of severe disease among pregnant individuals, neonates, and infants. Postpartum individuals with GBS are also at risk of endometritis and postoperative wound infections. In this study we describe demographics, clinical characteristics, and health care resource utilization among pregnant and postpartum women hospitalized with laboratory-confirmed invasive GBS (iGBS). Methods Individuals ≥18 years of age who had a positive GBS specimen collected from a sterile site during an inpatient admission were identified in the PINC AI™ Healthcare Database, which includes ∼1200 US hospitals, between 2016-2024 (index admission). Female patients who had a diagnosis and/or procedure code associated with pregnancy or delivery 0-42 days prior to index admission were categorized as pregnant or postpartum. We characterized maternal age, race, payor, and underlying health conditions 0-365 days before index admission. We also captured hospital length of stay, intensive care unit (ICU) admissions during index admission, and 90-day readmissions. Results We identified 150 pregnant and postpartum women hospitalized with iGBS between 2016-2024. Most women (81%) gave birth during the index admission, 8% were postpartum, and 11% were currently pregnant. Average age at admission was 29.4 years (standard deviation [SD] = 6.6 years). Half of women (53%) were White, 33% Black, 2% Asian, and 13% reported other or unknown race. Half of women (52%) were covered by commercial payors and 44% were Medicaid beneficiaries. The most common underlying health conditions were immune suppression (23%), obesity (15%), asthma (8%), and smoking (7%). The average length of the index admission was 5.2 days (SD = 5.0 days) and 13% of women were admitted to the ICU. In addition, 15% were readmitted to the same hospital < 90 days after discharge. Conclusion These analyses provide valuable information on iGBS disease during pregnancy and the post-partum period, and patient characteristics and health care utilization associated with this infection. Future analyses should focus on estimating disease incidence and assessing predictors of severe disease among women with iGBS to guide strategies for disease prevention. Disclosures Sarah Willis, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Katharina Schley, Dr. rer pol., Pfizer: Employee|Pfizer: Stocks/Bonds (Private Company) Eileen M. Dunne, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Kyla hayford, PhD, Pfizer: Stocks/Bonds (Public Company) Jennifer Moisi, PhD, Pfizer Vaccines: Employer|Pfizer Vaccines: Stocks/Bonds (Public Company)

Antibiotic resistance is increasing rapidly and is a major health problem worldwide. As a result, researchers are actively investigating safe and superior alternative therapeutic agents. Medicinal plants contain a wide array of bioactive compounds have found certain viability for such a purpose. Moringa oleifera is among such medicinal plants that exhibit several pharmacological features and are receiving attention for their antibiotic potential, represented by broad-spectrum antimicrobial action. The present review article emphasizes the antimicrobial potential of M. oleifera, highlighting the phytochemical profile, antibacterial mechanisms and its usage in the green synthesis of nanomaterials. The mentioned plant has a varied range of bioactive compounds e.g., flavonoids, glucosinolates, phenolic acids, alkaloids, sterols and terpenes that provide broad-spectrum antimicrobial activity by interfering with cell wall physiology, inhibiting protein synthesis and interfering with DNA replication. It has strong anti-quorum sensing and antibiofilm properties in addition to its direct antibacterial effects. The green synthesis of nanoparticles using M. oleifera has also been explored as a non-toxic and sustainable method of producing new antimicrobial materials. Overall, M. oleifera is a natural antibacterial agent that shows great promise and has a variety of therapeutic uses. Besides, antivirulence and nanotechnology approaches provide creative answers to address the rising issues of antibiotic resistance in current medicine.

Aim: To assess the predictive effect of threshold deviations for multiple liver biomarkers on negative clinical outcomes, including hepatic decompensation, liver transplantation, and death in patients with primary biliary cholangitis (PBC) using longitudinal data from a large administrative claims database. Materials & methods: A time-dependent Cox proportional hazards model with time-dependent covariates assessed time to first occurrence of hospitalization for hepatic decompensation, liver transplantation, or death in patients with PBC in the Optum Clinformatics Data Mart™ database. Separate models analyzed proportion of time outside prespecified biomarker thresholds (defined as multiples of upper limit of normal [ULN] for alkaline phosphatase [ALP], total bilirubin [TB], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]; lower limit of normal for albumin). Another model evaluated both ALP and TB with the lowest relevant threshold applied for each biomarker. Results: Overall, 2402 patients were included; 85.3% were female, mean age was 63.3years, median follow-up was 2.2years (interquartile range: 1.1-3.9years). On average, patients had approximately five reported measurements for each biomarker evaluated. Each 10% increase in time outside thresholds was associated with a 6.5%, 9.2%, 9.9%, 7.3% and 23.3% increase in risk of negative outcomes for ALP, TB, AST, ALT and albumin, respectively. Conclusion: In patients with PBC, values outside predefined thresholds for biomarkers including ALP, TB, AST, ALT and albumin strongly predicted negative clinical outcomes. These findings highlight the importance of managing biomarkers beyond ALP in monitoring and the treatment of patients with PBC.

Obesity significantly increases the risk of hyperlipidemia, type 2 diabetes, and liver disease. This study examined humanized monoacylglycerol acyltransferase 2 mice (HuMgat2) and their response to a high fat diet (HFD) while investigating hepatocyte dysfunction during obesity development. HuMgat2 mice fed a HFD exhibited hyperlipidemia, hyperglycemia, insulin resistance, and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of cholesterol and triglycerides were associated with increased expression of lipogenic genes and accumulation of nuclear Srebp1/Srebp2. Mice fed a HFD demonstrated impaired insulin signaling and increased glucose production through the expression of gluconeogenesis genes. Liver fibrosis was characterized by collagen deposition and activation of Jak2-Stat3 signaling, resulting in hepatocyte apoptosis. RNA sequencing identified extracellular matrix degradation and apolipoprotein metabolism as being altered. Levels of cytochrome P450 enzymes were downregulated, as indicated by decreased Cyp2b10 and Cyb3a11 levels, alongside reduced expression of the di- and tri-carboxylic acid transporter Slc13a2, correlating with elevated Krebs cycle intermediates. Notably, HuMgat2 mice exhibited responses to a high-fat diet that were comparable to those observed in mMgat2 mice. These findings suggest that HFD consumption and concomitant obesity disrupts metabolite homeostasis, contributing to liver damage and cell death. They also further validate HuMgat2 mice as an excellent preclinical model for testing human MOGAT2 inhibitors as therapeutics for treating obesity.