Elalfy, Aya

Background: Resistant hypertension (RH), defined as uncontrolled blood pressure (BP) despite ≥3 antihypertensive agents at maximally tolerated doses, remains a significant therapeutic challenge. Device-based renal denervation (RDN), using either radiofrequency (RF) or ultrasound (US) ablation, has shown promise in reducing BP. While both methods have demonstrated efficacy versus sham controls in randomized controlled trials (RCTs), direct comparisons remain limited. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of RF- and US-based RDN in patients with resistant hypertension. Methods: Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science through April 2025 for RCTs comparing RDN versus sham in RH. Eligible trials reported systolic or diastolic BP outcomes via ambulatory, office, or home measurements. Pooled mean differences (MD) and risk ratios (RR) were calculated using a random-effects model. Subgroup analyses were conducted by RDN modality and follow-up duration. Results: Seventeen RCTs met inclusion criteria. RDN significantly reduced ambulatory systolic BP (MD: −3.14 mmHg; 95% CI: −5.30 to −0.98; p=0.004) and diastolic BP (MD: −1.40 mmHg; 95% CI: −2.45 to −0.35; p=0.009) compared to sham. RF-based RDN showed consistent statistically significant reductions in both SBP and DBP across ambulatory and in-office measurements. In contrast, US-based RDN demonstrated variable efficacy, with only daytime DBP showing a marginal benefit (MD: −1.32 mmHg; p=0.04). Safety outcomes, including mortality, acute kidney injury, hypertensive crisis, and hypotension, were similar between groups. Conclusion: RDN offers a significant BP-lowering effect in resistant hypertension, with RF-based RDN yielding more consistent benefits across diverse measurement settings. US-based RDN showed limited but promising effects. Both techniques demonstrated acceptable safety profiles. Further head-to-head trials are needed to confirm long-term comparative effectiveness.

Introduction: Chronic total occlusion (CTO) is commonly encountered in patients with coronary artery disease and is associated with adverse outcomes, including increased short- and long-term mortality. While percutaneous coronary intervention (PCI) has shown potential clinical benefits in CTO patients, its comparative effectiveness against optimal medical therapy (OMT) remains debated. This meta-analysis aims to evaluate the impact of CTO-PCI versus OMT on key cardiovascular outcomes. Methods: We conducted a comprehensive search of Pubmed, Scopus, Web of science and Cochrane. We assessed outcomes including all-cause mortality, cardiac death, myocardial reinfarction, major adverse cardiac events (MACE), stroke, and repeat revascularization. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical significance was defined as p<0.05. Results: 25 studies with a total of 22102 patients were included. Compared to OMT alone, CTO-PCI was associated with a significant reduction in the overall all-cause mortality (RR: 0.66; 95% CI: 0.53–0.82; p=0.0002), cardiovascular mortality (RR: 0.65; 95% CI: 0.52–0.82; p=0.0003) and MACE (RR: 0.84; 95% CI: 0.71–0.98; p=0.03). No statistically significant differences were observed between CTO-PCI and OMT in rates of Stroke (RR: 1.01; 95% CI: 0.68–1.50; p=0.96), Subsequent PCI/CABG (revascularization) (RR: 1.01; 95% CI: 0.78–1.29; p=0.97) or Heart Failure Hospitalization (RR: 0.77; 95% CI: 0.37–1.59; p=0.48) Conclusion: This is the largest and most updated systematic review meta analysis for CTO-PCI vs OMT. Our findings show that CTO-PCI is associated with significantly lower all-cause and cardiovascular mortality compared to OMT. However, no significant differences were observed between the two strategies in the incidence of stroke, need for subsequent revascularization (PCI/CABG), or heart failure hospitalization.

ABSTRACT Background Pulmonary vein isolation is a standard therapy for paroxysmal atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel approach aiming to improve efficacy and safety over conventional thermal ablation (CTA) (radiofrequency and cryoballoon). This meta‐analysis evaluated outcomes of PFA versus thermal ablation in paroxysmal AF. Methods Electronic databases were searched through May 2025 for randomized controlled trials (RCTs) and observational studies that compared the efficacy and safety of PFA versus CTA. The primary outcome was AF recurrence. Summary estimates were conducted using random effects. Results A total of six studies, involving 1928 patients, were included. The incidence of AF recurrence was significantly lower among patients treated with PFA (risk ratio [RR] 0.67; 95% confidence interval [CI] 0.53–0.85). PFA was associated with a lower incidence of any atrial arrhythmia recurrence (RR 0.78, 95% CI: 0.61–0.99). The total procedure duration was significantly shorter with PFA (mean difference −21.46 min (95% CI: −26.04 to −16.88)), but there was no difference in fluoroscopy time. The rates of esophageal injury and phrenic nerve palsy were lower with PFA. However, the data were limited for these two outcomes, and a meta‐analysis was not conducted for them. There was no difference between the two groups in the incidence of stroke or pericardial tamponade. Conclusion Among patients with paroxysmal AF undergoing catheter ablation, PFA is associated with favorable outcomes, including lower recurrence and shorter procedure time compared to conventional ablation modalities.

e16330 Background: Sarcomatoid hepatocellular carcinoma (SHC) is a rare and aggressive variant of hepatocellular carcinoma (HCC), accounting for less than 2% of all primary liver cancers. Characterized by the presence of both epithelial and mesenchymal components, SHC demonstrates a high degree of cellular plasticity, often associated with epithelial-mesenchymal transition. This phenotypic heterogeneity contributes to its aggressive clinical behavior, including rapid tumor progression, early metastasis, and poor response to conventional therapies. As a result, patients diagnosed with SHC typically have a median survival of less than 12 months, significantly lower than that observed in patients with conventional HCC. Methods: We conducted a retrospective study at the Mayo Clinic Comprehensive Cancer Center, focusing on patients diagnosed with SHC between April 2017 and December 2023. The data collected included demographics, performance status, underlying risk factors, alpha-fetoprotein (AFP) levels, next generation sequencing (NGS) testing, and the treatment received. Results: A total of ten patients with confirmed diagnoses of SHC were included, with median age at the time of diagnosis 63.5 years (37-77), predimonantly male (9 out of 10), and identifying white (8 out of 10). Alcoholic cirrhosis was identified as an underlying risk factor in three patients, NASH cirrhosis in two, and HCV in two patients. The majority (6 out of 10) of the patients had localized disease, with 4 patients having denovo metastatic disease with abdominal lymph node involvement. Five patients had NGS testing (Tempus, Guardant 360, and ProvsSeq523), with resultant pathogenic variants including TP53 in 3 patients, NTRK3 fusion, IDH2, EGFR, TERT, MLH1, ARIS1A, and PALB2. Four patients were treated with combined Yitrrium-90 and systemic therapy. Three patient started systemic therapy, and two patients underwent surgical resection. Systemic Therapy used included combined Atezolizumab/ Bevacizuamab, Pembrolizumab/ Lenvatinib, Gemcitabine/ Docetaxel, Gemcitabine/ Cisplatin, Cabozantinib, and pembrolizumab monotherapy. The median overall survival for this group was 11.5 months; 95% confidence interval (CI): 4.66-40.1 months. Seventy percent experienced progression, with a median progression-free survival after first line of treatment of 2.5 months; 95% CI: 1-15.3 months. Conclusions: Sarcomatoid HCC remains aggressive and difficult to treat cancer with limited overall survival. Immunotherapy based regimens have limited efficacy for this HCC variant.

e16265 Background: The pivotal TOPAZ-1 trial established durvalumab plus gemcitabine and cisplatin (GC) as a new first-line standard of care for advanced biliary tract cancer (ABTC). However, weekly administration of GC can lead to significant toxicity limiting its tolerability in clinical practice. Based on previous studies, we implemented biweekly regimen of GC on days 1 and 15 together with durvalumab on day 1 of each 28-day cycle to optimize the treatment delivery and improve tolerability. Here, we report the Mayo Clinic experience with biweekly GC with monthly durvalumab in patients with ABTC. Methods: At our three-site institution, we retrospectively identified patients with ABTC between January 2021 and August 2024, who received biweekly GC with monthly durvalumab. Patient demographics, tumor characteristics, treatment details - treatment related adverse events (trAEs) graded according to the NCTCAE V5.0 were collected. Outcomes included median progression-free survival (mPFS), median overall survival (mOS) and clinically assessed overall response rate (ORR) and disease control rate (DCR). Results: 57 patients were included in our analysis, median age was 68 years (range 35-90), and 57.9% were females. 91.2% of patients had ECOG performance status of 0-1. 71.9% had intrahepatic cholangiocarcinoma, 19.3% extrahepatic cholangiocarcinoma and 8.7% gallbladder carcinoma. 70.2% had metastatic disease, 21 % locally advanced unresectable disease and 8.7% recurrent metastatic disease. Patients were followed for a median of 9.1 months (2.3-28.5). 91.2% of the patients received biweekly GC plus monthly durvalumab while 8.8% switched from weekly to biweekly GC plus monthly durvalumab due to treatment toxicities. Median number of treatment cycles was 5. Maintenance regimens included durvalumab (19.3%), gemcitabine/durvalumab (8.8%) and GC/durvalumab (8.8%). Median duration of follow up was 9.1 months (range 2.3 – 28.5). ORR was 36.9% and DCR was 72% (complete response 5.3%, partial response 31.6% and stable disease 35.1%). mPFS was 7.2 months, while mOS was 16 months. Grade(G) 3 or 4 trAEs included abnormal liver function tests (15.7%), infections (11.5%), anemia (8.7%), thrombocytopenia (5.2%), peripheral neuropathy (1.7%), acute kidney injury (1.7%). Immune-related AEs were noted in 6 patients (10.5%) including colitis, gastritis, hepatitis, myocarditis and hypothyroidism. There was no patient with severe neutropenia or febrile neutropenia. Only 5 patients (8.8%) stopped treatment due to trAEs. Conclusions: Biweekly GC on days 1 and 15 plus durvalumab on day 1 of each 28-day cycle is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in the TOPAZ-1 trial indicating that a de-escalation strategy is feasible with improvement in patient centered outcomes.

10587 Background: The American Society of Clinical Oncology (ASCO) and NCCN recommend germline testing for patients (pts) with biliary tract cancers (BTC), particularly those diagnosed at a young age. Prior studies estimate that approximately 15% of pts with BTC harbor pathogenic germline alterations. Germline testing can identify hereditary cancer syndromes, guide targeted therapy, and inform family counseling. This study aimed to further characterize and describe the prevalence of pathogenic germline variants (PGVs) in patients with young-onset BTC (YO-BTC). Methods: We conducted a retrospective review of medical records for pts diagnosed with YO-BTC (ages 18–55) across all Mayo Clinic tri-sites from January 2014 to October 2024. Data collected included results from germline DNA sequencing, tumor genetic testing, demographics, history of other malignancies, and family history of cancer. The primary outcome was the identification of pathogenic germline mutations associated with cancer predisposition. Results: Among 239 pts with YO-BTC, the median age at diagnosis was 43 years (range 19–55), with 62% female and 65.2% identifying as white. Clinical germline testing (e.g., Invitae, Ambry, Myriad) was performed in 123 pts (51.5%), revealing PGVs in 15 pts (12.1%), variants of uncertain significance (VUS) in 30 pts (24.3%), and likely benign variants in 4 pts (3.2%). Among those with PGVs, DNA repair mutations were the most common findings (10/15), including ATM (4), CHEK2 (2), BRCA2 (2), BAP1 (1), and PALB2 (1). One pt had a Lynch syndrome-associated mutation (MSH6), and four had mutations in other cancer-related genes (MUTYH, HOXB13, RMRP, and PIK3CA). Tumor genomic profiling (via CARIS, TEMPUS, or FoundationOne) was performed in 9 pts with PGVs, detecting the variant in 4 (44%), while liquid biopsy (Guardant) identified the PGV in 4 of 6 cases (66.6%).The majority of PGV carriers had advanced BTC (14/15), with intrahepatic cholangiocarcinoma being the most prevalent (11/15), while 4 had extrahepatic cholangiocarcinoma. Additionally, most PGV carriers had a first- or second-degree relative with a prior history of malignancy (14/15), and 3 pts had a second malignancy. Of the 15 pts with PGVs, 4 had BTC associated with primary sclerosing cholangitis. Conclusions: In this large institutional series of YO-BTC, PGVs were identified in 12.1% of pts, demonstrating a significant yield from germline testing in this population. Notably, tissue and liquid biopsies demonstrated different detection rates for PGVs, underscoring the variability in PGVs reporting across platforms. Germline testing through CLIA-approved methods should remain the standard of care. DNA repair pathway mutations, particularly ATM, CHEK2, and BRCA2, were the most frequently identified PGVs, highlighting their role in the pathogenesis of YO-BTC and their potential to guide treatment decisions.