Citations

11549 Background: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a subset associated with unicentric Castleman disease (UCD). However, the impact of CD association on clinicopathologic features and survival outcomes remains unclear. This study aims to elucidate differences in disease characteristics and outcomes in FDCS with and without CD to guide future research and clinical practice. Methods: We retrospectively analyzed 41 FDCS patients seen at Mayo Clinic between January 2000 and December 2024. Patients were categorized into CD-related (n = 9) and FDCS-only (n = 32) groups. Demographic, clinical, pathological, and survival data were compared. Kaplan-Meier survival analyses were used to evaluate overall survival (OS) and progression-free survival (PFS). Epstein-Barr virus-associated inflammatory FDCS were excluded. Results: The CD-related group was younger at diagnosis (46.0 vs. 58.0 years, p = 0.041). Among those with CD-related FDCS, FDCS was diagnosed concurrently as CD in 6/9 (66.7%) and after the diagnosis of CD in 3/9 (33.3%). The FDCS-only patients were more likely to have extranodal disease (71.9% vs. 22.2%) and to have metastasis (62.5% vs 22.2%). One CD-related FDCS patient had paraneoplastic pemphigus. Among 11 patients with next-generation sequencing (NGS) results, 9 had pathogenic mutations. The most common pathogenic mutations included CDKN2A, CDKN2B, and TRAF3 copy number losses. Surgery was the preferred first-line intervention in FDCS-only and CD-related FDCS groups (19/32, 59.4% vs. 6/9, 66.7%). Eight out of 32 (25.0%) of the FDCS-only group received chemotherapy at first-line, most commonly Gemcitabine/Docetaxel or Adriamycin/Ifosphamide. While Gemcitabine/Docetaxel was the most preferred in the second line, different regimens were pursued in the third and later lines of therapy, including Pembrolizumab, Pazopanib, and stem cell transplant. Five out of 6 patients in the CD-related FDCS group received either adjuvant radiation or chemotherapy, which led to complete remission during the follow-up periods. The median follow-up was 22.4 months for the whole population. There was a trend for better OS and PFS among CD-related FDCS patients. The respective 2-year OS rates were 100% and 66.7%, and 2-year PFS rates were 57.1% and 43.1% for CD-related FDCS and FDCS-only patients, respectively. Conclusions: This study provides novel insights into clinicopathologic differences and survival trends for FDCS. Our data would suggest a less aggressive disease course among CD-related FDCS, which implies the need for different treatment strategies for CD and non-CD-related FDCS. Further research is warranted to elucidate these mechanisms, such as multi-omic analysis on benign FDC proliferation in the microdissected UCD areas and the adjacent FDCS cells to determine factors associated with progression to sarcoma.

e14601 Background: Immune checkpoint inhibitors (ICIs) provide a long-term survival benefit across multiple cancer types, however immune-related adverse events (irAEs) occasionally disrupt treatments and impact quality of life. Peripheral edema from ICIs can occur due to increased peripheral vascular permeability. Thus, we aimed to evaluate the incidence and outcomes of ICI-related peripheral edema. Methods: MEDLINE, Embase, and Web of Science were searched to identify phase 3 randomized controlled trials (RCTs) reporting peripheral edema events in patients treated with ICIs. Incidence rates of peripheral edema were analyzed based on treatment patterns (monotherapy/combination therapy) and ICI subtypes (PD-1/PD-L1/CTLA-4). A random effect model meta-analysis was utilized to calculate pooled odds ratios of edema incidence between treatment groups. Finally, a systematic review was conducted to summarize treatment outcomes of peripheral edema associated with ICIs. Results: Overall, 58 RCTs comprising 22,590 patients were identified for the incidence analysis. Peripheral edema as treatment-related adverse events (TRAE) (Grade 1-5) occurred in 2.80% of patients receiving ICI monotherapy (n = 195/6969; PD-1 inhibitors: 2.22% [n = 104/4694], PD-L1: 3.73% [n = 58/1557], CTLA-4: 4.60% [n = 33/718]), 4.96% (n = 112/2257) of patients receiving ICI with chemotherapy, and 8.73% (n = 205/2349) of patients receiving ICI with molecular-targeted therapy. Grade 3-5 TRAE peripheral edema occurred in 0.19% (n = 13/6969) of patients treated with ICI monotherapy. Meta-analysis showed ICI monotherapy had lower TRAE peripheral edema compared to chemotherapy (OR = 0.45, 95% CI [0.27, 0.73], p = 0.001). Subgroup analysis based on ICI subtypes showed high heterogeneity in subgroups (p , I 2 = 87.1%), but PD-1 inhibitors were associated with lower incidence than chemotherapy (OR = 0.41, 95% CI [0.23, 0.73], ). Subgroup analysis of chemotherapy regimens revealed that taxane chemotherapy was associated with a higher incidence of TRAE peripheral edema than ICI monotherapy (OR = 0.32, 95% CI [0.18, 0.58], p = < 0.001), but the edema incidence was comparable between ICI monotherapy and non-taxane chemotherapy (OR = 1.05, 95% CI [0.53, 2.08], p = 0.13). A systematic review of irAE peripheral edema treatment outcomes identified 19 studies comprising 40 patients. In total, 82.5% (n = 33/40) of cases received glucocorticoid treatment, with 55.0% (n = 22/40) requiring a high dose (≥ 1 mg/kg/day) of prednisone. ICI was discontinued in 77.5% of patients (n = 31/40) due to peripheral edema with permanent discontinuation in 35% (n = 14/40). Conclusions: Peripheral edema is an occasional but clinically significant side effect of ICI therapy. Management of irAE edema can result in permanent ICI discontinuation, which has implications for cancer treatment outcomes.

e13738 Background: Persistent racial/ethnic and regional disparities in neoplasm mortality remain significant public health challenges. This study evaluates long-term trends in neoplasm mortality by race/ethnicity at the county level in the United States and examines the relationship between hospital density and mortality. Methods: Using data from the Global Burden of Disease Study (2000-2019), we analyzed age-standardized mortality rates (ASR) for neoplasms by ethnicity/raceHispanic (all races) and non-Hispanic American Indian or Alaska Native (AIAN), Asian or Pacific Islander (API), Black, and White. A joinpoint regression analysis was used to identify significant changes in the mortality trends, summarized as average annual percent change (AAPC). Correlation analysis evaluated the relationship between county-level hospital density and neoplasm mortality. Results: Neoplasm mortality rates declined across all racial/ethnic groups from 2000 to 2019, but disparities persisted. ASR per 100,000 population decreased from 240.5 (95% UI: 214.3–269.9) to 203.0 (180.8–228.3) for AIAN, 149.5 (144.9–153.9) to 115.3 (111.7–118.7) for API, 314.5 (312.1–317.0) to 218.7 (217.1–220.3) for Black, 168.4 (164.6–172.0) to 133.8 (131.0–136.4) for Latino, and 241.2 (240.5–242.0) to 187.5 (186.9–188.2) for White. AAPC from 2000 to 2019 ranged from -0.94% (AIAN) to -1.90% (Black). Gender-specific analyses revealed similar trends, with males showing slightly greater declines. Southeast states experienced slower declines compared to the Northeast. Some counties exhibited worsening mortality trends, particularly for AIAN, API, and Latino. The county-level hospital density (table) showed weak but statistically significant correlations in 2019 for AIAN (r = -0.35; p < 0.0001), White (r = -0.15; p < 0.0001), and Black (r = -0.18; p < 0.0001). No inverse correlation was observed for API (r = 0.07; p = 0.071) and Latino (r = 0.06; p = 0.012). Conclusions: While significant progress has been made in reducing neoplasm mortality, racial/ethnic and regional disparities persist, and health care access appears to contribute to this at least in part. Future analyses should evaluate mortality by cancer site and also account for broader clinical and public health infrastructure, as well as social determinants of health to better understand and address underlying disparities. The correlation between hospital density and age-standardized mortality rate from neoplasms by race/ethnicity in 2019. Correlation coefficient with mortality and hospital density AIAN API Black Latino White 2019 -0.35(-0.43 – -0.27) 0.069(-0.0058–0.14) -0.18(-0.23 –-0.13) 0.064(0.014–0.11) -0.15(-0.19 – -0.12)

e15003 Background: Antibody-drug conjugates (ADCs) have shown substantial promise as therapies for metastatic breast cancer (mBC). However, direct comparisons of different ADC-based regimens are limited. We assessed survival outcomes in mBC patients treated with ADCs. Methods: Randomized controlled trials (RCTs) published before October 2024 were searched in Medline, Embase, ClinicalTrials.gov, and Cochrane Library. Progression-free survival (PFS) and overall surcvival (OS) outcomes were extracted from the most updated publications. Participants were stratified based on molecular subtypes, hormone receptor (HR) status, duration of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment, and sensitivity to endocrine therapy (ET). Bayesian frameworks were deployed, presenting the synthesized outcomes of indirect comparisons using the surface under the cumulative ranking curve (SUCRA), hazard ratio (HR), and 95% credible interval (Crl). This study was prospectively registered on the International Platform of Registered Systemic Reviews and Meta-analysis Protocols (INPLASY) (INPLASY2024110021). Results: A total of 6449 patients from 12 RCTs of ADCs ado-trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), and datopotamab deruxtecan (Dato-DXd) were included in the analysis. Compared to chemotherapy, T-DXd significantly improved PFS (HR 0.35, 95% Crl 0.15-0.84) and OS (HR 0.56, 95% Crl 0.32-1.0). SG also significantly extended OS (HR 0.65, 95% Crl 0.43-0.97) but not PFS. In HER2+ mBC, pooled analyses revealed T-DXd was the most effective treatment in terms of PFS, with a SUCRA of 94.2%, followed by T-DM1 (58.9%), and chemotherapy with HER2-directed therapy (34.2%). Synthesized outcomes of OS mirrored the PFS outcomes. In HR+/HER2- mBC (some of which was HER2-low), Dato-DXd (76.1%) showed slightly superior efficacy over SG (67.4%) for PFS, while SG (85.1%) was advantageous over Dato-DXd (49.1%) in terms of OS. Among patients with HR+/HER2+ mBC, T-DXd (80.0%), SG (55.5%), and chemotherapy with HER2-directed therapy (53.1%) were the most effective therapies for prolonging PFS. Regarding OS, SG (70.3%) and T-DM1 (60.3%) were the most effective, with comparable efficacy observed between chemotherapy with HER2-directed therapy (52.1%) and T-DXd (52.0%). In HR-/HER2+ mBC, T-DXd (78.1%), SG (56.1%), and T-DM1 (51.5%) significantly prolonged PFS, while SG (69.4%) had the most substantial benefit for OS, followed by T-DXd (62.8%) and chemotherapy with HER2-directed therapy (57.6%). Dato-DXd showed an advantage over SG in mBC patients received CDK4/6i for > 12 months. Conclusions: This network meta-analysis showed prominent survival benefits with ADC-containing regimens for mBC. Our results provide valuable insights into personalized treatment strategies for mBC patients.

Purpose To compare the outcomes of standard combined Phaco-Kahook Dual Blade (KDB) surgery (GI) with those of the extended technique (GII). Methods This retrospective, comparative, multicenter, case-control study enrolled patients with one-year follow-up. GI removed 90° of the trabecular meshwork (TM) extension during KDB, whereas GII removed 150°. The successful criteria were based on a modification of the AAO PPP recommendations - Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery. Qualified success was achieved with or without medication, while absolute success was achieved without the use of any ocular hypotensive medication. Results A total of 72 eyes (36 in both groups) were included. The IOP was similar between groups preoperatively (GI: 17.0 ± 2.7 mmHg vs. GII: 17.5 ± 4.2 mmHg, p = 0.5), and at 12 months postoperatively (GI: 13.5 ± 2.8 mmHg vs. GII: 12.3 ± 2.7 mmHg, p = 0.06). The number of glaucoma medications was reduced from 1.7 ± 0.9 to 0.4 ± 0.8 in GI ( p < 0.001) and from 2.1 ± 0.8 to 0.4 ± 0.7 in GII ( p < 0.001). At 12 months, both groups reduced comparable glaucoma medications ( p = 0.9). Qualified success was achieved in 77.1% of the eyes with GI and 94.4% with GII ( p = 0.03), whereas complete success was achieved in 68.6% of the eyes with GI and 69.4% with GII ( p = 0.7). No serious complications were observed in any of the groups. Conclusion Extended combined Phaco-KDB surgery showed greater relative success than the Standard Phaco-KDB technique. Both techniques achieved similar IOP reduction at 12 months postoperatively.

Abstract Rationale: Although guidelines recommend the use of provocative testing to diagnose pulmonary venous hypertension (PVH) that is unapparent at normal resting right heart catheterization (RHC), the incremental value of provocative testing is unknown. We aim to evaluate the incremental diagnostic capability of inhaled nitric oxide (iNO), fluid challenge (FC) or invasive cardiopulmonary exercise testing (iCPET) to unmask PVH using previously defined hemodynamic cutoffs. Methods: We included subjects from the NHLBI-funded Pulmonary Vascular Disease Phenomics (PVDOMICS) study. Our analysis included patients with World Symposium on Pulmonary Hypertension (WSPH) Group 2 disease (G2PH) and G2PH comparators (WSPH Group 2 phenotype without a diagnosis of PH) as determined by the PI or adjudication panel. We then applied a protocol-driven provocative approach based on the feasibility of modalities available in most catheterization labs. Using a pulmonary capillary wedge pressure (PCWP) cutoff of &gt;15, frequencies were identified for subjects based on resting PCWP and with iNO. Frequencies were also identified for: those who received FC with a PCWP cutoff of ≥18 or those who received iCPET with PCWP cutoff of &gt;20 (upright) or &gt;25 (supine). Results: There were 419 subjects identified with WSPH Group 2 disease (Figure). Roughly half were found to have a PCWP &gt;15 during resting RHC (N = 207). Of the remaining subjects with a resting PCWP ≤15 (N = 150), 42 subjects were found to have a PCWP &gt;15 with iNO administration (40.0%). Of the remaining 63 subjects with PCWP ≤15 following iNO administration, nearly half (N = 26, 48.0%) demonstrated a PCWP ≥18 following FC while 8 subjects (14.8%) demonstrated an elevated PCWP following iCPET. Conclusions: There is a high proportion of G2PH patients (∼35%) who appear hemodynamically similar to precapillary PH at rest. Inhaled nitric oxide vasodilatory challenge unmasks G2PH in many patients. In situations where iNO does not disclose the G2PH phenotype, provocation with FC or iCPET can be useful as a supplementary provocative maneuver. Future directions will focus on agnostically assessing the utility of provocation based on grouping subjects by resting hemodynamics as well as assessing the use of provocation in other forms of PH.

ABSTRACT Background The assessment of aortic stenosis (AS) severity remains a challenge in some patients, and hemodynamic exercise testing has been proposed as a diagnostic tool in this population. However, the current understanding of exercise hemodynamics in AS is limited. Methods Retrospective review of 34 adults (aged ≥ 18 years) with ≥ moderate AS and preserved left ventricular ejection fraction (LVEF) undergoing exercise invasive hemodynamics (supine cycle protocol) with simultaneous measurement of aortic and left ventricular pressures. Results Age was 77.1 (IQR 68.6; 84.1) years, and 50% were female. LVEF was 62.1 ± 6.6%. All patients were symptomatic. Resting aortic valve area (AVA) was 1.0 ± 0.2 cm 2 and aortic valve (AV) systolic mean gradient 22.0 ± 7.3 mmHg. At peak exercise (40 [IQR 30; 60] W), AV systolic mean gradient (Δ3 [0.6; 7] mmHg, p < 0.001) and AVA (Δ0.2 [0; 0.6] cm 2 , p = 0.002) significantly increased, while stroke volume (SV) did not (Δ6.8 ± 19.4 ml; p = 0.07). Exercise‐induced changes in AV systolic mean gradient were directly related to changes in cardiac output ( r = 0.53, p = 0.003), being inversely related to exercise systemic vascular resistance ( r = −0.60, p = 0.002). Elevated pulmonary artery wedge pressure was present in 41.2% at rest (≥ 15 mmHg) and 69.7% during exercise (≥ 25 mmHg). Conclusions Symptomatic patients with ≥ moderate AS and preserved LVEF experience small increases in AV mean gradient with exercise, and unlike the normal physiological response to exercise, there was no significant increase in SV. In most patients, AVA rose during exercise. Exercise‐induced elevation in filling pressures was highly prevalent.

This Viewpoint discusses the use of aortic valve intervention vs watchful waiting for patients with asymptomatic aortic stenosis.