Citations

Abstract Background: Sexual and gender minority (SGM) representation is growing in the United States. This study estimated the future SGM cancer burden amidst shifting cancer patterns. Methods: Age-specific incidence data for breast, prostate, colorectal, lung, and melanoma were obtained from the Surveillance, Epidemiology, and End Results Program’s 12-registry database. Nordpred age-period-cohort models projected incidence through 2040 to 2044. Rates were applied to US Census population estimates and generation- and sex-specific SGM identification proportions from Gallup’s 2023 to 2024 surveys. Prophet was used for sensitivity analysis. Results: At ages 55 to 59, breast cancer cases among Millennial SGMs were 3,672% higher than among Silent Generation SGMs (34,850 vs. 924 cases), melanoma cases were 1,061% higher (5,526 vs. 476 cases), and colorectal cancer cases were 2,206% higher (23,594 vs. 1,023 cases). Compared with Generation X, Millennial prostate cancer cases were 142% higher (8,100 vs. 3,344 cases), and lung cancer cases were 169% higher (5,451 vs. 2,029 cases). By 2040 to 2044, Millennials were projected to account for 68.4% of breast cancer cases and 59.7% of colorectal cancer cases among SGMs. Conclusions: At ages 55 to 59, the 5-year cancer burden was projected to be 15 times higher among Millennials than Silent Generation SGMs (77,521 vs. 5,134 cases), driven primarily by the larger SGM population in younger generations. Oncology systems will need to prepare for the increase in cancer care demand. Impact: These findings identify a substantial generational shift in the SGM cancer burden and may inform oncology workforce capacity, culturally responsive cancer care, and healthcare system preparation for this growing population.

Context.— Transporting specimens can expose them to uncontrolled environmental factors. Whole blood viability is a commonly used preanalytic marker of quality for analysis of white blood cells. Objective.— To evaluate whole blood viability as a marker for transportation and specimen integrity for lymphocyte subset evaluation. Design.— More than 9000 whole blood specimens, transported during a 4-year period, and their lymphocyte subset evaluation results were analyzed retrospectively. Viability was measured by using Cellaca MX imaging cytometer, and lymphocyte and lymphocyte subset counts were determined with flow cytometry. Specimen cell viability results were stratified based on different transportation factors to discern their potential effects. Lymphocyte subset evaluation results from specimens with lower viability were compared with those from optimal viability specimens. Results.— Cell viability of transported specimens exhibited seasonal variation, decreasing during the warm summer months (median, 77.0% versus 83.4% in other seasons). The decline in viability negatively correlated with ambient temperature during transportation ( r = −0.7876). Longer transportation time (>60 hours) also caused a decrease in viability (median, 64.0%). While we observed a decrease in absolute cell counts for CD45 + lymphocytes, CD3 + T cells, CD8 + T cells, and CD19 + B cells in specimens with low viability (50%–80%), the differences were well within the assay’s total allowable error. Conclusions.— Control of preanalytic factors is critical for laboratory testing. Whole blood viability is a sensitive indicator of transport conditions and time, but it is not a specific predictor of quality for the main lymphocyte populations in cellular immunology testing.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

e19094 Background: WM/LPL is an indolent B-cell Non-Hodgkin Lymphoma with prolonged survival and predisposition to secondary malignancies (SM) influencing clinical outcomes and survivorship care. We evaluated the incidence, demography, treatment utilization, and outcomes of SM in patients with WM/LPL using population-based data. Methods: SEER-22 database was used to identify patients with LPL/WM diagnosed between 2000–2022 and stratified by SM. Overall survival (OS) was analyzed using Kaplan–Meier survival analysis and propensity score matched Cox regression was used to assess mortality risk. Hazard ratios were reported, with p<0.05 deemed significant. Results: 22,170 patients with WM/LPL were identified, with a median age of 71 years (IQR 16); the cohort was predominantly male (59.0%), White (84.0%), had a median household income of $50,000–$75,000 (48.9%), and resided primarily in urban areas (89.5%). Among all WM/LPL patients, 20.8% (n=4,615) developed a SM. Patients who developed SM were older than those without (median age 75 vs 70 years, p<0.0001) with 45.2% alive at predefined follow-up. The most common solid organ SM were gastrointestinal adenocarcinoma (16%), prostate cancer (14%), and lung adenocarcinoma (9%), while the leading hematologic SM were plasma cell myeloma (6%), diffuse large B-cell lymphoma (5%), and myelodysplastic syndrome (2%). 35.3% of the cohort received chemotherapy, while 0.1% received cancer-related surgery or radiation. On multivariable analysis, older age (OR 0.82, 95% CI 0.81–0.83), male sex (OR 0.59, 95% CI 0.44–0.80), urban residence (OR 1.99, 95% CI 1.24–3.18), and higher income (OR 2.16, 95% CI 1.13–4.15) were significantly associated with SM diagnosis. Kaplan–Meier analysis demonstrated inferior survival among patients with SM (54.8% vs 45.2%, p<0.0001), with shorter median OS (9 vs 14 years, log-rank p<0.001). Similarly, Propensity-matched analysis revealed worse OS in patients with SM (HR 1.15, 95% CI 1.09–1.22, p<0.001). Median OS varied substantially by SM site (see Table). Conclusions: Our study demonstrates a substantial burden of SMs among patients with WM/LPL and are associated with substantially inferior survival despite the indolent nature of the disease. The marked heterogeneity in SM types and outcomes highlights the need for risk-adapted surveillance, survivorship-focused care, and equitable strategies to address disparities and improve long-term outcomes in this population. SM Site Median OS (years) IQR p-value Hepatopancreatobiliary 1 0 <0.05 CNS 3.5 9 <0.05 Breast 3 6 <0.05 Colorectal 4 3.5 <0.05 Lymph Node 5 8 <0.05 Blood 6 7 <0.05 Lung 7 9 <0.05 Head & Neck 6.5 8.5 <0.05 Melanoma 9 10 <0.05 Urogenital 10.5 7 <0.05

e14111 Background: Primary CNSL (PCNSL) is a rare, aggressive B-cell non-Hodgkin lymphoma limited to the CNS, while secondary CNSL (SCNSL) represents CNS involvement from systemic lymphoma. Previous observations focused on CNSL have limited data clinically comparing PSNSL and SCNSL. We aimed to evaluate overall survival and associated factors in patients with PCNSL vs SCNSL using a large population database. Methods: We conducted a retrospective cohort study using the SEER-22 database to identify patients diagnosed with CNSL between 2020-2022. Group comparisons used t-tests or ANOVA for continuous variables, chi-square tests for categorical variables, and Kaplan–Meier survival analysis, with all analyses performed in RStudio 4.1.1 and significance deemed as p<0.05. Results: 14,964 patients with CNS lymphoma were identified, with 84.6% PCNSL and 15.4% SCNSL cases. The overall median age was 65 years (IQR 20), with 52% male, 66% White patients, residing in urban areas (90%) and median household income of $50,000–$75,000 (52%). Compared with PCNSL, patients with SCNSL were significantly older (72 vs 64 years, p<0.0001). SCNSL more frequently involved the cerebrum (39% vs 34%) and cerebellum (5.5% vs 4.5%), but less commonly affected the nerves (12.0% vs 12.5%) and spinal cord (4.2% vs 5.1%) (p<0.05). Disease was predominantly unilateral (95.8%) in both groups. Chemotherapy (55% vs 56%) and radiotherapy (19% vs 18%) utilization did not differ significantly, with external beam radiation comprising 94.3% of radiated cases. PCNSL patients were more likely to undergo surgical intervention than SCNSL patients (31.8% vs 28.7%; p=0.0027). Diffuse large B-cell lymphoma was the most common histologic subtype in both PCNSL (70.1%) and SCNSL (74.3%). Median overall survival was shorter in SCNSL (1.64 years) than PCNSL (1.99 years). Survival improved significantly across diagnostic eras (2000–2005 to 2016–2020; log-rank p<0.001), while lower income (<$50,000) and rural residence were associated with inferior outcomes (p=0.028 and p=0.033). Conclusions: Survival in CNS lymphoma remains poor, with SCNSL associated with worse outcomes compared with PCNSL. Greater understanding of treatment variation and disease differences is needed to optimize therapy and improve patient outcomes. Characteristic PCNSL SCNSL Total p-Value N 12667 2297 14964 Population Distribution 0.033 Urban 11426 2038 13464 Rural 1241 259 1500 Surgery 0.0027 Yes 3630 730 4360 No 9037 1567 10604 Months from Diagnosis to Rx(Mean, SD) 0.31 (0.86) 0.27 (0.65) 0.30 (0.83) 0.0077 Death Status <0.0001 Dead 8603 1772 10375 Alive 4064 525 4589 Overall Survival (in years, Mean, SD) 1.99 (2.85) 1.64 (2.31) 1.93 (2.77) <0.0001

Abstract Background X‐ray Induced Acoustic Computed Tomography (XACT) is an emerging imaging technique that provides 3D volumetric images from a single projection by detecting X‐ray‐induced acoustic (XA) waves with ultrasound (US) transducers. Unlike MRI or CT, XACT enables real‐time 3D imaging without long acquisition times, 2D limitations, or motion artifacts from mechanical rotation. Furthermore, when integrated with conventional pulse‐echo US through time‐sequenced operation, XACT provides complementary soft‐tissue contrast, establishing it as a promising platform for dynamic interventional radiology (IR) guidance. Purpose This study aims to evaluate the feasibility of XACT as a novel imaging tool for IR, specifically for guiding needle placement and monitoring contrast agent dynamics. Methods We developed a 3D XACT imaging system equipped with a 256‐element 2D matrix array and a portable X‐ray tube to visualize needle insertion and contrast agent dynamics. To capture both needle position and soft tissue anatomy, we integrated a dual‐modality system combining XACT with pulse‐echo US using a 128‐element linear US array. Experiments were conducted on both tissue‐mimic phantoms and soft tissue samples. GPU‐accelerated algorithm has been developed for 3D XACT image reconstruction. Results The results demonstrate the 3D capabilities of XACT imaging for interventional procedures, including monitoring of needle placement and tracking of contrast agent dynamics. The imaging speed reached up to 3∼4 s per frame, constrained by the repetition rate of the X‐ray source and signal to noise ratio. The dual‐modality approach provided clear visualization of the needle's position and the surrounding soft tissue structures, achieving imaging resolution around 2 mm. Conclusions This study demonstrates that XACT imaging is feasible to be used for IR. Its 3D imaging capability with faster imaging speed would be an alternative to cone beam CT and its capability to combine US imaging will provide richer information for soft tissue

Abstract Blood-based biomarkers show promise as a noninvasive method for measuring Alzheimer’s disease pathology and neurodegeneration throughout the lifecourse. However, the relationship between longitudinal changes in these biomarkers and late-life brain morphology in community-dwelling populations requires further investigation. Between 2011 and 2013, 1,977 participants from the Atherosclerosis Risk in Communities Study received underwent 3 Tesla magnetic resonance imaging scans. Whole-brain cortical thickness was quantified by Freesurfer. Stored plasma samples collected in midlife (1993-95, mean age 59.0 years) and late-life (2011-13, mean age 76.8 years) from a subsample of 1,515 participants (60.7% female, 25.5% Black adults) were assayed in 2022 using Quanterix SiMoA. The assay quantified amyloid-β (Aβ)42/40, phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Linear regression models estimated the association of blood-based biomarkers from midlife, late-life, and the change from midlife to late-life with cortical thickness in late-life. In models adjusted for demographics, lifestyle factors, cardiovascular factors, and the presence of APOE ε4 alleles, higher midlife measures of p-Tau181 and increases from midlife to late-life in NfL and GFAP were associated with lower cortical thickness in late-life. Concurrent measures of p-Tau181, NfL, and GFAP were associated with lower cortical thickness in late-life and exhibited a stronger association among participants ≥75 years old compared to participants &lt;75 years old. Additional longitudinal research is needed to determine whether blood-based biomarkers predict cortical thinning over time and may serve as an early indicator of accelerated brain atrophy.

Abstract Introduction: Primary central nervous system T-cell lymphoma (PCNSTL) is a rare form of PCNSL, comprising 2–8% of cases. Prognostic factors remain undefined, and no standard treatment protocol currently exists. Prior studies have been limited by small sample sizes, incomplete molecular profiling, and poor representation of novel treatment modalities. In this study, we aimed to identify clinicopathologic factors associated with patient (pt) outcomes and delineate the spectrum of treatment regimens used to inform future clinical practice. Methods A multicenter retrospective study was conducted across 15 North American academic institutions. Pts aged ≥18 years with biopsy-confirmed PCNSTL between 2009 and 2025 with no evidence of systemic disease were included. Cases with CNS relapse of systemic T-cell lymphoma were excluded. Baseline characteristics were analyzed using independent t-tests, Fisher's exact tests, or Pearson's chi-square tests. Primary endpoints were overall survival (OS) and progression-free survival (PFS), evaluated by Kaplan–Meier, log-rank tests, and Cox regression. Results: Forty-two pts met inclusion criteria. Median age was 57 (range 19–77), 69% were male, and 79% were white. Most (69%) had ECOG 0–1. No patients had HIV, hepatitis B or C, or a history of solid organ transplant. LDH was elevated at diagnosis in 38%, and 24% had B-symptoms. Mean absolute lymphocyte count at diagnosis was 1.82/µL. The most common histologic subtypes were PTCL-NOS (76%), followed by ALK-negative ALCL (12%) and γδ T-cell lymphoma (5%). All patients had parenchymal brain lesions with 57% having multifocal disease. Additionally, CSF involvement was seen in 21%, vitreoretinal involvement in 3%, and deep brain involvement in 34%. Next-generation sequencing was performed in seven pts (17%), with disease-associated variants identified in three cases. Among these, two pts had mutations in TP53, and one had a mutation in DNMT3A. Cytogenetics were obtained in 7 pts with only one exhibiting a complex karyotype. Only one pt was EBV positive by EBER-ISH. Overall, 79% received HD-MTX-based therapy. First-line treatments were mainly HD-MTX alone (38%), HD-MTX + temozolomide (17%), or vincristine + procarbazine (12%). No patients were treated on clinical trials. Median treatment duration was 78 days and median number of treatment cycles was 4 (range 1–9 cycles). One patient received radiation alone; 5% received radiation with systemic therapy. A steroid pre-phase was used in 60%, with 44% exhibiting a clinical response. Overall response rate to first-line treatment was 63% (13 CR, 12 PR). Imaging alone was used in determining response in all patients. Repeated biopsy was not performed. Twelve patients (29%) underwent consolidative autologous transplant, most commonly with thiotepa/carmustine (TT/BCNU, 69%) or BEAM conditioning (25%). Median duration of follow-up was 10.4 months. Sixty-two percent of pts progressed during the study period, with 7% experiencing extra-CNS relapse. Median PFS was 8.2 months. Improved PFS was associated with &gt;3 cycles of therapy (p=0.03) and transplant with TT/BCNU (p=0.0004). At last follow-up, 43% were in remission and 52% were deceased, mostly due to disease progression (77%). Median OS was 17.6 months. One- and two-year OS rates were 58% and 42%, respectively. OS was associated with Nottingham/Barcelona score &lt;2 (p=0.02), &gt;3 treatment cycles (p=0.0008), response to first-line therapy (p=0.0007), and TT/BCNU-based transplant (p=0.0001). IELSG, Taipei, and MSKCC risk scores were not significantly associated with survival, though IELSG approached significance (p=0.09). Discussion: This study is among the largest cohorts of PCNSTL pts compiled to date. PCNSTL remains rare and heterogenous. Treatment across centers largely mirrors management of B-cell PCNSL with high utilization of HD-MTX regimens and TT/BCNU conditioning autologous transplant. Survival outcomes within our cohort are consistent with those previously reported within the literature. Receipt of &gt;3 cycles of therapy, TT/BCNU conditioning and Nottingham/Barcelona scores were associated with longer survival within our cohort. Limitations of our study include its retrospective design and heterogeneity within pt disease characteristics, treatments utilized and disease assessment intervals. Further exploration into pathophysiology and optimal management of this unique entity is needed.