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Comparative effectiveness and toxicity of CAR-T therapy versus blinatumomab in adult B-cell acute lymphoblastic leukemia: A real-world propensity-matched analysis.

6551 Background: Chimeric antigen receptor T-cell (CAR-T) therapy and blinatumomab are established treatment options for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). While CAR-T therapy offers durable disease control, it is associated with significant immune-mediated toxicities, including cytokine release syndrome (CRS) and neurotoxicity. Comparative real-world data evaluating long-term mortality and toxicity outcomes between CAR-T therapy and blinatumomab remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Analytics Network. Adult patients with B-cell acute lymphoblastic leukemia treated with either CAR-T therapy or blinatumomab were identified. Propensity score matching (1:1) was performed to balance baseline demographic and clinical characteristics, yielding 306 patients in each cohort. Primary outcomes included all-cause mortality at 1 and 3 years. Secondary outcomes included cytokine release syndrome at 1 year and neurotoxicity (including delirium, encephalopathy, and altered mental status) at 3 months, 1 year, and 3 years. Outcomes were assessed using risk ratios (RR), odds ratios (OR), Kaplan–Meier survival analysis, and Cox proportional hazards models. Results: After propensity matching, 612 patients were analyzed (306 per cohort). At 1 year, all-cause mortality was significantly higher with CAR-T than blinatumomab (50.98% vs 17.97%; RR 2.84, 95% CI 2.18–3.69; p<0.0001). Kaplan–Meier analysis showed inferior survival with CAR-T (HR 3.48, 95% CI 2.56–4.74; log-rank p<0.0001). This excess mortality persisted at 3 years (52.61% vs 18.95%; RR 2.78, 95% CI 2.15–3.58; p<0.0001; HR 3.43, 95% CI 2.54–4.63). CAR-T was associated with higher cytokine release syndrome at 1 year (20.59% vs 5.88%; RR 3.50, 95% CI 2.12–5.77; p<0.0001). Neurotoxicity was consistently more frequent with CAR-T: 27.78% vs 13.40% at 3 months (RR 2.07, 95% CI 1.48–2.91; p<0.0001), 25.16% vs 11.44% at 1 year (RR 2.20, 95% CI 1.52–3.18; p<0.0001), and 27.78% vs 13.40% at 3 years (RR 2.07, 95% CI 1.49–3.15; p<0.0001). Kaplan–Meier analyses confirmed a persistently higher cumulative neurotoxicity risk with CAR-T across all time points. Conclusions: In this large real-world propensity-matched analysis, CAR-T therapy for B-cell ALL was associated with significantly higher short- and long-term mortality compared with blinatumomab, as well as markedly increased risks of cytokine release syndrome and neurotoxicity. These findings highlight the substantial toxicity burden associated with CAR-T therapy in routine clinical practice and underscore the importance of careful patient selection, early toxicity recognition, and risk-benefit stratification when choosing between advanced immunotherapeutic options for B-ALL.

Buried-interface homogenization by asymmetric polymeric self-assembled layers powers efficient, durable flexible perovskite photovoltaics

Initial phase 1b/2 study results of purinostat mesylate (PM) in combination with pomalidomide (POM) and low dexamethasone (DEX) in patients with RRMM.

TPS7581 Background: MM remains an incurable disease and resistance mechanisms are emerging. PM is a high selective HDAC I/IIb inhibitor. In phase I study, PM monotherapy had shown good tolerability and efficacy in relapsed/refractory (RR) hematologic malignancies including MM. A phase 1b/2 study is being conducted to further assess the efficacy and safety of PM combined with POM and low DEX (80mg/cycle) in RRMM. Methods: The ongoing phase 1b/2 study includes dose escalation followed by dose expansion. Eligible RRMM had received ≥1 prior line of therapy (LOT) including ≥1 PI and ≥1 IMiD. Cohort A (21D cycle) and Cohort B (28D cycle) of the PM combination regimens are assessed using 3+3 escalation design. Pts in Cohort A receive PM at levels of 4, 6, 8.4, 11.2 and 15mg/m 2 IV on D1,4,8,11; POM 4mg QD on D1-14; DEX 20mg on D1,4,8,11. Pts in Cohort B receive PM at same dose range to Cohort A, on D1,4,15,18; POM 4mg QD on D1-21; DEX 20mg on D1,4,15,18. Pts continue to receive PM until disease progression or unacceptable toxicity. Primary outcomes are DLT and ORR. Secondary outcomes include PFS et al. Results: As of Dec 23, 2025, 27 Pts were recruited including 6 in Cohort A and 21 in Cohort B. The dose had been escalated to 6mg/m 2 and 11.2mg/m 2 in Cohort A and B. Cohort A: Median age was 61.5 years, 66.7% male, 16.7% had prior ASCT. 2 (33.3%) Pts had high risk cytogenetics, including 1q21 duplication (n=1), t (4;14) (n=1) and 1p32 deletion (n=1). 6 Pts were evaluable with median 1 (1-3) prior LOT. The ORR was 50% with 1 sCR and 2 PR along with 1 MR. With a median F/U of 138 days, the median PFS was 151 days (95% CI, 21-NR). Median DOR was NR. The most common ≥ G3 TEAEs were neutropenia (83.3%), lymphocytopenia (83.3%) and thrombocytopenia (100%). No DLT was reported. Cohort B: Median age was 61.0 years, 57.1% male, 19.1% had prior ASCT and 19.1% had extramedullary disease (EMD). 7 (33.3%) Pts had high risk characteristics, including 1q21 duplication (n=7), t (4;14) (n=2) and early relapse after ASCT (n=3). Median prior LOT is 2 (1-5). Among 16 evaluable Pts, the ORR was 37.5% with 1 sCR, 1 CR, 3 VGPR and 1 PR; additional 4 Pts achieved MR. In 7 Pts given the dose of 8.4mg/m 2 , the ORR was 42.9% with 3 VGPR; 3 more Pts achieved MR. With median F/U of 104 days, the median PFS and DOR were NR. The most common ≥ G3 TEAEs were neutropenia (81.0%), lymphocytopenia (61.9%) and thrombocytopenia (38.1%). 1 DLT (G4 neutropenia) was reported. Moreover, in 4 Pts with EMD, 2 achieved objective response. In 4 Pts with super high risk (Double or Triple Hit/early relapse), 1 achieved sCR and 1 achieved VGPR. 1 Pt with prior 5-line therapy including BCMA-ADC had shown VGPR after treatment. Conclusion: PM as a highly selective HDACi in combination with POM and low DEX shown encouraging efficacy and safety in RRMM. Complicated cases with EMD, super high-risk characteristics or heavily pretreatment can benefit from the PM triplet therapy. Clinical trial information: NCT06484829 .

Use of palliative radiation and association with end-of-life quality metrics and healthcare utilization for patients with gynecologic malignancies in Ontario, Canada from 2006-2018.

e24055 Background: The optimal use of radiotherapy at the end of life (EOL) is undefined in gynecologic oncology. We investigated the use of radiotherapy at the EOL in patients with gynecologic malignancies, and relationship to established EOL healthcare quality indicators. Methods: A population-based, retrospective cohort study of gynecologic cancer decedents in Ontario, Canada from 2006-2018 using ICES-linked administrative health care data. Results: Of 16,237 decedents, 26.7% received palliative intent radiotherapy; 6.7% received late radiation in the last 31-90 days (d) of life, and 5.3% received EOL radiation in the final 30d. Radiation was most frequently received by patients with non-ovarian malignancies, and the most common site was pelvis (44.2%). Late radiation was initiated a median 10 (IQR 8-12) weeks before death, and these patients received median 20Gy (IQR 8-24) over median 6 (IQR 3-10) fractions. EOL radiation was initiated a median 3 (IQR 2-5) weeks before death, and these patients received median 16Gy (IQR 8-20) over median 6 (IQR 2-8) fractions, accounting for 20% of remaining days of life. On multivariable analysis, age <40 years, non-ovarian cancers, stage IV disease at diagnosis were associated with receipt of late and EOL radiation. Patients receiving late radiation had the lowest rates within the last 30 days of life of hospitalization (45.7% vs. 70.6% with EOL radiation and 56.6% with neither), ICU admission (2.8% vs. 5.8% with EOL radiation vs. 4.1% with neither), death in hospital (36.3% vs. 55.3% with EOL radiation vs. 44.7% with neither), and the composite measure of aggressive EOL care (15.6% vs. 27.3% with EOL radiation vs. 20.7% with neither). They also had a higher likelihood of receiving early palliative care ≥3mo before death (68.1% vs. 50.8% with EOL radiation vs. 62.9% with neither). On multivariable logistic regression, late radiation remained significantly associated with less aggressive care, more supportive care, and lower risk of death in hospital, while EOL radiation was significantly associated with more aggressive care and higher risk of death in hospital. Conclusions: One quarter of gynecologic cancer decedents receive palliative radiotherapy, with 12.1% in the final 90 days of life. Dose schedules did not differ between those receiving late vs. EOL radiation; however, late palliative radiation was associated with less aggressive EOL healthcare utilization and more supportive care, while EOL radiation was associated with the highest rates of individual and aggressive EOL care metrics.

Population-based breast cancer incidence by age, sex, subtype, and stage.

e22620 Background: Granular estimates of breast cancer incidence by age, sex, molecular subtype, and stage are essential for understanding disease burden and informing prevention, screening, treatment, and research priorities. Registry-based data provide clinical detail but reflect a subset of the U.S. population, while nationally representative estimates often lack comparable granularity. Methods: We analyzed data from eligible Surveillance, Epidemiology, and End Results (SEER) cancer registries and the Global Burden of Disease (GBD) 2023 study to estimate age- and sex-specific breast cancer incidence by molecular subtype and stage in the United States. SEER data were used to derive subtype and stage distributions within by year, age, and sex. Stage categories included localized, regional, and distant disease, consistent with SEER Summary Stage definitions.Year-specific SEER subtype and stage-within subtype distributions were used directly. For strata with missing estimates, distributions were imputed using a stepwise approach, prioritizing estimates from a recent reference year (2017) and, if unavailable, pooled estimates across years within the same age and sex group. Distributions were then temporally smoothed using LOWESS on the logit scale with renormalization. After harmonization by location, year, age, sex, and cancer type, GBD incidence estimates were proportionally redistributed using the smoothed SEER-derived subtype and stage-within-subtype distributions to generate nationally representative incidence estimates. Results: This approach enabled nationally representative quantification of absolute breast cancer burden by molecular subtype, stage, and finer age groupings not available from registry data alone. In 2022, a substantial portion of the national burden occurred among women aged 50–69 years. Within this age range, HR+/HER2- disease accounted for the greatest number of incident cases, with an estimated 29,309 cases (95% UI: 25,189–33,731) among women aged 65–69 years (incidence rate: 298 per 100,000). HR-/HER2- disease also contributed substantial burden in this age group (3,611 cases; 95% UI: 3,103–4,156; incidence rate: 37 per 100,000). In contrast, HER2+ subtypes peaked at younger ages within the 50–69 range. Across molecular subtypes, localized-stage disease accounted for the largest proportion of incident cases. Conclusions: Integrating registry-derived subtype and stage distributions with nationally representative incidence estimates enables more granular characterization of breast cancer burden than registry data alone. These population-based estimates may inform national cancer surveillance and research prioritization by aligning incidence burden with clinically relevant subtype and stage stratifications.

Demographic and regional trends in combined colorectal cancer and cerebrovascular disease-related mortality in the United States (1999–2023).

e15715 Background: Prior studies suggest substantial cerebrovascular disease (CVD) comorbidity among patients with colorectal cancer (CRC). However, national long-term mortality trends involving combined CRC and CVD causes of death remain poorly characterized. This study aimed to analyze demographic and regional patterns trends in combined CRC and CVD- related mortality in the United States (US) from 1999 to 2023. Methods: We analysed CDC WONDER Multiple Cause-of-Death Public Use record death certificates (1999–2023) for adults aged ≥55y. Death certificates listing CRC (ICD 10: C18-20) and CVD (ICD-10: I60-I69) as either contributing or underlying causes of death were identified. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated and stratified by year, sex, race, census region, state, and metropolitan status. Temporal trends were assessed using Joinpoint regression to estimate the annual percent change (APC) with 95% confidence interval (CI). Results: A total of 47,638 deaths listing CRC and CVD occurred during study period. AAMR declined from 4.51 in 1999 to 1.96 in 2020 (APC -3.95%; 95% CI -4.60 to -3.30), with a rapid early reduction from 1999–2016 (APC −5.64%; 95% CI -5.95 to -5.32), followed by a modest rebound from 2016–2021 (APC +3.82%; 95% CI 0.30 to 7.48), and a subsequent stabilization from 2021-2023 (APC −2.99%; 95% CI -12.7 to 7.79). Males had higher AAMR than females (3.23 vs 2.29), while females experienced a faster decline in mortality [APC −4.14%; 95% CI -4.81 to -3.45 vs APC −3.84%; 95% CI -4.45 to -3.22) [Table]. Black individuals had the highest AAMR (3.61), followed by White (2.48), Asian/Pacific Islander (1.72), and American Indian/Alaska Native populations (1.69), with Asian/Pacific Islanders demonstrating the steepest decline (APC −5.04%; 95% CI -6.03 to -4.03). Regionally, Midwest had the highest AAMR (2.89), while the Northeast showing the steepest decline (APC −4.64%, 95% CI -5.20 to -4.08). Non-metropolitan areas had higher mortality rates than metropolitan areas (AAMR 3.30 vs 2.55). Conclusions: Although combined CRC and CVD- related mortality among older adults has declined substantially over the past two decades, persistent sociodemographic and regional disparities remain. These findings may highlight the potential importance of integrating cardiovascular risk assessment and prevention strategies into CRC survivorship and cardio-oncology care models. Annual percentage change in combined colorectal cancer and cerebrovascular disease related mortality among patients aged ≥ 55 in the US (1999-2023). Variable Deaths Annual Percentage Change (95% CI) Overall 47,638 -3.95 ( -4.60 to - 3.30) Male 22,947 -3.84 (-4.45 to -3.22) Female 24,691 -4.14 (-4.81 to -3.45) White 40,416 -3.89 (-4.54 to -3.24) Black or African Americans 5,985 -3.82 (-4.56 to -3.08) Asian or Pacific Islander 938 -5.04 (-6.03 to -4.03)

Allele-specific targeting of CD33 as a novel approach to enhance CAR-T selectivity in relapsed acute myeloid leukemia post–allogeneic transplantation.

6554 Background: Relapse after allogeneic hematopoietic cell transplant (HCT) represents the most common treatment failure in acute myeloid leukemia (AML), urging the need for new therapies. Chimeric antigen receptor (CAR) T cells have shown efficacy in lymphoid and plasma cell malignancies but have not yet successfully translated to myeloid disease. This could in part be due to the expression of target antigens on normal myeloid cells, which might result in significant on-target but off-tumor effects. Exploiting a single nucleotide polymorphism (SNP) in SIGLEC3 , which encodes CD33, to target relapsing AML cells while selectively sparing donor-derived hematopoietic cells could improve the efficacy of anti-CD33 CAR-T cells in treating AML. Methods: We evaluated the in vitro efficacy and specificity of CAR-T cells that target each of two alleles of a common SNP in CD33 (rs2455069, CD33 Arg69Gly ). Controls included untransduced activated T-cells (UTD, negative control) and CAR-T cells targeting a different CD33 epitope (CART33 Pan positive control). Effector cells were incubated with CD33-expressing AML targets for 24 hours at serial effector-to-target ratios, and surviving target cells were quantified via flow cytometry to calculate percent cell killing. Initial screens used Jurkat cells lentivirally transduced with CD33 of each polymorphism (Jurkat33 Gly or Jurkat33 Arg ) to characterize CAR-T efficacy and specificity. Subsequent tests used MOLM-13 (homozygous CD33 Arg ) and KG-1 (homozygous CD33 Gly ) AML cell lines. Statistical comparisons of generated CAR-T cytotoxicity curves were performed with two-way ANOVA. Killing assays were performed with at least six biologic replicates. Results: CART33 Gly and CART33 Arg cells each showed statistically equivalent killing against their concordant Jurkat33 targets compared to CART33 Pan cells. Each CAR directed minimal killing of discordant Jurkat33 targets, similar to UTD controls. In KG-1 (CD33 Gly ) cells, CART33 Gly showed similar killing efficacy as CART33 Pan cells, while CART33 Arg were statistically equivalent to UTD cells at multiple E:T ratios. In MOLM-13 (CD33 Arg ) cells, CART33 Gly and CART33 Arg exhibited mixed efficacy and specificity: at lower E:T ratios (1:16 to 1:8), CART33 Gly was statistically equivalent to untransduced controls, but began to demonstrate more nonspecific toxicity at E:T above 1:4. CART33 Arg exhibited significant cytotoxicity once above E:T of 1:8, but only achieved similar toxicity to CART33 Pan at E:T ratios over 1:2. Conclusions: Allele-specific CART33 cells demonstrate promising efficacy and specificity in killing AML cells expressing either CD33 Gly or CD33 Gly . Further studies are underway to test efficacy in vivo against primary AML cells and safety toward normal hematopoietic progenitor cells that express the alternative CD33 allele.

Association of SARS-CoV-2 vaccination with survival outcomes in patients with metastatic solid tumors treated with immune checkpoint inhibitors.

2591 Background: Patients with cancer experience disproportionately high morbidity and mortality from SARS-CoV-2 infection, and COVID-19 vaccination is recommended for all patients with cancer. Although vaccines primarily reduce infection related complications, emerging data suggest SARS-CoV-2 mRNA vaccines may also enhance antitumor immune responses and potentially synergize with immune checkpoint inhibitors (ICIs). We evaluated survival outcomes in vaccinated versus unvaccinated patients with metastatic solid tumors treated with immunotherapy. Methods: Data for adults with metastatic cancers for which ICIs are indicated were obtained from the TriNetX Research Network (2019–2024). Patients were classified by receipt of ≥1 SARS-CoV-2 mRNA vaccine around the time of ICI initiation (±1 year) and compared with unvaccinated patients. Those with prior systemic antineoplastic, endocrine, or immunosuppressive therapy before ICI initiation or who developed COVID-19 were excluded. Cohorts were propensity matched for demographics, cancer type, comorbidities, and laboratory values. Outcomes included overall survival at 90 days, 1 year, and 5 years using Kaplan–Meier analyses, and all-cause hospitalization and immune-related adverse events (irAEs) within 90 days. Results: After matching, 543 vaccinated and 543 unvaccinated patients were well balanced. Vaccination was not associated with increased irAEs, with similar rates of any irAE (19.0% vs 17.9%, p=0.64), gastrointestinal (3.87% vs 3.87%, p=1.00), dermatologic (11.8% vs 10.7%, p=0.56), and neurologic events (2.76% vs 2.39%, p=0.70); pulmonary and hepatic irAEs were rare. Hospitalization rates were comparable (24.9% vs 23.9%, p=0.72). Vaccinated patients demonstrated improved intermediate-term survival, with higher 1-year survival (73.35% vs 64.12%; HR 0.70, 95% CI 0.56–0.87, p=0.001), with trends toward benefit at 90 days (HR 0.69, p=0.053) and 5 years (HR 0.85, p=0.066). Landmark analysis from 1 to 5 years showed no significant survival difference (HR 1.15, p=0.34). Consistent 1-year survival benefits were observed in lung cancer (65.93% vs 52.56%; HR 0.63, p=0.0005) and melanoma (80.25% vs 68.65%; HR 0.56, p=0.0355). Conclusions: In this large propensity-matched real-world cohort of metastatic solid tumor patients receiving immune checkpoint inhibitors, COVID-19 vaccination was not associated with increased immune-related toxicity or hospitalization and was associated with significantly improved 1-year overall survival. Attenuation of the survival association in landmark analyses suggests potential time-related bias, supporting the need for further studies with precise exposure timing.

Assessing burden and outcomes: Colon cancer survival across the U.S. safety-net spectrum.

11176 Background: Safety-net hospitals (SNHs) provide essential care for uninsured and underinsured patients but often face systemic constraints that may affect cancer outcomes. Colon cancer, a leading cause of cancer-related death in the United States, requires complex multidisciplinary management. This study assessed the association between hospital safety-net burden and clinical outcomes in colon cancer across a national dataset. We also identified patient-level factors contributing to disparities in care delivery. Methods: Using the National Cancer Database (NCDB), we identified approximately 1.2 million adult patients diagnosed with colon cancer in the United States between 2004 and 2020. Facilities were stratified by safety-net burden into Non–Safety-Net Hospitals (NSNH; < 25% Medicaid/uninsured cases), Safety-Net Hospitals (SNH; 25–75%), and Extreme Safety-Net Hospitals (Extreme-SNH; > 75%). This safety-net spectrum provided a novel framework for capturing both facility- and patient-level disparities that influence colon cancer care and outcomes. Multivariable logistic and Cox regression models were used to evaluate differences in disease stage, treatment timelines, and survival, adjusting for age, comorbidity, and AJCC stage. Kruskal–Wallis and chi-square tests were used for descriptive analyses. Results: SNHs and Extreme-SNHs cared for a greater proportion of patients with advanced-stage disease, lower rates of chemotherapy, immunotherapy, and palliative care utilization, and higher short-term mortality when compared with NSNH. Thirty-day readmission rates after surgery were similar across groups. Survival analyses demonstrated a graded decline in outcomes with increasing safety-net burden: median overall survival was 91.2 months in NSNH, 83.6 months in SNH, and 70.9 months in Extreme-SNH (p < 0.001). One-year survival exceeded 95% across all facilities, but five-year survival declined to 68.9% for NSNH vs 59.4% for Extreme-SNH. Additional disparities in colon cancer outcomes were observed by health literacy level, residential setting (urban, metropolitan, rural), race, age, and sex. Conclusions: Colon cancer patients treated at hospitals with higher safety-net burden experience substantially poorer long-term survival despite comparable short-term outcomes. These findings highlight the need for targeted policy, resource allocation, and quality-improvement efforts to reduce disparities and strengthen oncology care delivery in high-burden safety-net systems. A Plan–Do–Check–Act (PDCA) approach tailored to individual hospital settings and regional contexts may help identify gaps in colon cancer care and guide targeted interventions to improve patient outcomes.

Social deprivation index (SDI) as a predictor of racial and ethnic disparity in a large real world cancer database.

e23429 Background: Healthcare access and representation can vary significantly by race, ethnicity and neighborhood deprivation. SDI calculation incorporates factors like poverty, education, employment, housing, transportation and family structure associated with residential zip codes. Here we investigated the association between SDI and race/ethnicity for the most common cancer types in the US. Methods: Patients with Bladder (n = 11,148), Breast (n = 34,285), Colorectal (CRC, n = 48,998), Endometrial (EMCA, n = 26,290), Kidney (n = 5,991), Non-small cell lung cancer (NSCLC, n = 72,397), Melanoma (n = 11044), Pancreatic (n = 19,444) and Prostate (n = 16,170) cancers were included from Caris Life Sciences (Phoenix, AZ) with NGS (NGS-592, WES) sequencing. Race and ethnicity was self-reported. Genetic ancestry (GA) was inferred by 36,962 ancestry-informative variants derived from globally diverse Genome Aggregation Database (gnomAD) reference individuals (n = 4,150). 3-digit residential zipcodes were extracted and paired with publicly available SDI (US Census Bureau). Prevalences were calculated across SDI quartiles (Q1-4). Significance was calculated by chi-square with Benjamini-Hochberg corrections. Results: Across all cancer types SDI Q4 was associated with a greater proportion (%) of Black/African American (BAA) and Hispanic or Latino (H/L) patients (all q < 0.001). When incorporating genetic ancestry data, there was also a greater proportion of patients with African (AFR) ancestry and Indigenous Americans (AMR) ancestry with increased SDI quartile (Q4 vs Q1 q < 0.001) (Table 1). Conclusions: Location-based disadvantage is racialized/ethnicized across cancers as B/AA, H/L patients and those with AFR and AMR ancestry are disproportionately more populated in high deprivation neighborhoods (SDI Q4). This disparity may represent barriers to precision oncology access and can severely bias genomic evidence and should be accounted for in translational research. Proportion of each racial/ethnic characteristic by SDI Quartile by cancer. (Q-values compare Q1 vs Q4, all q<0.001. Headers annotated as "Characteristic: SDI Quartile".). Cancer BAA: Q1% BAA: Q2% BAA: Q3% BAA: Q4% H/L: Q1% H/L: Q2% H/L: Q3% H/L: Q4% AFR: Q1% AFR: Q2% AFR: Q3% AFR: Q4% AMR: Q1% AMR: Q2% AMR: Q3% AMR: Q4% Bladder 13 20 25 42 11 17 19 52 13 21 26 40 12 18 23 47 Breast 15 19 23 43 13 17 25 45 15 20 24 40 13 17 29 42 CRC 13 20 24 43 12 19 24 46 14 21 25 40 12 19 25 44 EMCA 13 20 25 43 12 18 20 50 14 20 25 40 12 20 23 45 Kidney 14 19 20 47 15 17 22 46 17 18 19 46 17 18 22 43 NSCLC 15 19 24 41 10 14 25 51 10 26 26 39 9 16 24 51 Melanoma 12 17 23 49 12 15 23 51 12 19 24 45 11 15 28 45 Pancreatic 13 19 25 43 12 15 23 50 13 19 26 42 13 15 27 46 Prostate 14 16 23 47 13 15 24 48 14 17 25 44 13 16 23 48

Convenience vs. complexity: Adoption of subcutaneous PD-(L)1s in lung cancer in EU4+UK.

3083 Background: Subcutaneous (SC) PD-(L)1 formulations represent a significant step towards simplifying treatment administration by reducing treatment time, compared to intravenous (IV) preparations. To date, the EMA has approved three SC PD-(L)1s: atezolizumab, nivolumab, and pembrolizumab. Here, we evaluate how the availability of SC formulation is affecting physicians’ prescribing behaviour, the drivers of the switch from IV to SC, and potential barriers affecting decisions in the treatment of lung cancer in EU4+UK. Methods: The Ipsos’ Global Oncology Monitor is a physician-reported syndicated patient record database. This analysis comprises 2,537 cancer-treating physicians in EU4+UK, screened for seniority and caseload, submitting data on 36,383 lung cancer patients, online, from January 2024 to November 2025. Physicians who treated lung cancers also completed a perceptual questionnaire on SC PD-(L)1 usage in lung cancer. Responses were collected from 150 physicians in EU4+UK, online, from October to December 2025. Results: Adoption of SC PD-(L)1 in lung cancer in EU4+UK is at 6% in the 3 months ending November 2025 compared to 94% of the IV format. We observed that SC PD-(L)1 was more likely used as monotherapy while the IV formulation in combination therapy (Table 1). Among patients receiving the IV version, 13% have a planned switch to SC, 71% do not, while 16% remained classified as the physician being undecided. Of those who would switch/undecided, the switch was estimated to happen after a mean of 4.5 cycles on the IV formulation. Conclusions: In this study, the uptake of SC PD-(L)1 reflects its clear benefit in reducing treatment time; however, the IV formulation remains dominant, suggesting physician hesitancy toward the SC format. While shorter administration time is beneficial, it does not yet outweigh concerns regarding patient comfort. Crucially, SC usage is notably lower in combination therapies compared to monotherapy. This suggests that when IV chemotherapy is required, the convenience of an SC add-on is diminished. Furthermore, the perception that SC offers ‘no additional value’ over the established IV contributes to this inertia. To drive adoption and improve patient experience, manufacturers must address administration-related discomfort and effectively communicate the comparative efficacy and workflow benefits of the SC formulation, particularly for patients who have yet to switch. Further investigation to assess any country differences and patient point of view will be beneficial. Usage of PD-(L)1 by formulation. Subcutaneousn=123 Intravenousn=1,914 Monotherapy 72% 41% Combination 28% 59%

New oral SERD plus CDK4/6 inhibitors in recurrent or metastatic ER+/HER2- breast cancer: A systematic review and single-arm meta-analysis.

e13072 Background: Hormone-positive breast cancer is prone to late recurrence and is biologically heterogeneous. The advent of selective estrogen receptor degraders (SERDs), such as fulvestrant, has improved treatment for metastatic disease. However, resistance to hormones and ESR1 mutations continues to impede disease control. Emerging drug combinations aim to address these obstacles while avoiding more systemic chemotherapy. We analyzed the efficacy of novel oral SERDs combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in recurrent or metastatic hormone-positive breast cancer. Methods: We searched for randomized clinical trials that reported the use of new oral SERDs combined with CDK4/6 inhibitors in patients with recurrent or stage IV breast cancer, using the PubMed, Cochrane, and Embase databases up to December 2025. The primary efficacy endpoints were Objective Response Rate (ORR), Clinical Benefit Rate (CBR), and Progression-Free Survival (PFS) in both intention-to-treat and ESR1 mutation-positive patients. Considering safety, we assessed treatment-related adverse events (TRAEs) by any grade and grade 3. Statistical analysis was performed using R software. We analysed heterogeneity with I² statistics and pooled proportions using a random-effects model. Results: We included six prospective studies with 1178 patients that met eligibility criteria. The pooled median PFS was 10.09 months (95% CI 6.79 - 15, I² = 88.7%), while subgroup analysis of patients in second-line endocrine therapy has a similar PFS of 10.26 months (95% CI 5.80 - 18.17, i² = 91,1%). The ORR was 21.90% (95% CI 13.37- 33.77, I² = 84.5%) and CBR 68.97% (95% CI 53.33-81.22, I² = 92.3%). Patients harboring ESR1 mutations present a median PFS of 11.61 months (95% CI 7.81-17.21, I² 83.5%). TRAEs by any grade were 89.17% (95% CI 66.67- 97.13, I2 = 95.1%), while grade 3 were 49.42% (95% CI 31.88-67.10, I2 = 88.6%). Conclusions: The combination of new oral SERDs and CDK 4/6 inhibitors in hormone-positive breast cancer constitutes a promising and effective strategy for metastatic disease control with manageable toxicity. Addressing the ESR1 mutational profile is crucial to optimizing the impact of this therapeutic approach.

Correction: Reconsidering the context in the relationship between material deprivation and self-rated health among older people in Italy

An implantable acoustofluidic chip for on-demand and programmable drug delivery

Clinical drug delivery requires precise control, yet conventional methods suffer from fluctuating concentrations and low bioavailability. While implantable devices are promising for long-term therapy, wireless dosage control remains challenging. We report an implantable acoustofluidic chip for on-demand drug delivery. Fabricated via soft lithography and two-photon polymerization, the device integrates a drug-loaded hydrogel and a sharp-edge microcantilever array within a polydimethylsiloxane microchannel. Wireless ultrasound actuation induces acoustic streaming via the microcantilever array, generating a net pumping flow to drive drug release. In addition, the device also enables liquid-phase medications to be controllably released when the drug-loaded hydrogel is replaced by a liquid-phase formulation. Biocompatibility evaluation over a 144 h cell co-culture period confirms negligible cytotoxicity of the acoustofluidic chip. This work demonstrates a promising strategy for wireless, programmable implantable drug delivery.

Mangrove-derived nanoparticles: A review of synthesis and biomedical applications

Toward Human Thermal Comfort: An Adaptive Solar‐Radiative Thermoregulator

ABSTRACT While adaptive thermoregulators are promising green solutions for buildings, current designs often focus solely on air temperature, neglecting the multifaceted nature of human thermal sensation. Here, we proposed a thermal‐comfort‐oriented design paradigm that integrates responsiveness to multiple environmental stimuli, including temperature, humidity, and solar irradiance. We demonstrated a proof‐of‐concept thermoregulator capable of perceiving environmental changes and adjusting its configuration accordingly, offering a stepless thermal regulation potential within a range of 824 W m −2 (heating) to −114 W m −2 (cooling). Field tests affirmed that model houses with this intelligent thermoregulator could maintain thermal comfort for up to 6 h with zero energy consumption during the daytime. The device also exhibited exceptional mechanical strength, adhesion properties, and resistance to adverse weather conditions, ensuring its service reliability. Simulations indicate the device can reduce energy consumption by 15%–50% compared to standard roofs while maintaining indoor thermal comfort across different climates worldwide, highlighting the great potential of multi‐stimuli‐responsive thermoregulators for building thermal management.

Moderate shading improves photosynthetic growth traits and phenanthrene production in Oreorchis patens

Golgi-derived phosphatidylinositol 4-phosphate is crucial for organization of the preautophagosomal structure

Association of carbon tetrachloride with lung cancer incidence and mortality, including effects in low-smoking regions.

8076 Background: Although cigarette smoking is the main risk factor for lung cancer, 10–20 percent of cases occur in non-smokers, with women disproportionately affected. This pattern suggests that community-level environmental exposures may contribute to lung cancer risk beyond smoking. Methods: In this ecologic, county-level study, average age-adjusted lung cancer incidence from 2017–2021 and sex-specific smoking prevalence were obtained from the NCI State Cancer Profiles. County-level exposure data were derived from the EPA National Air Toxics Assessment, with 73 air toxics screened to identify the most strongly associated pollutant. The leading exposure was evaluated in sex-stratified multivariable spatial error regression models adjusting for smoking prevalence and key county-level covariates, including radon, PM 2.5 , Social Vulnerability Index (SVI). Analyses included 2,042–2,238 U.S. counties. Additional models were fit separately within strata of smoking prevalence to compare associations across lower and higher-smoking counties. Results: Among 73 EPA-tracked air toxins, carbon tetrachloride (CCl 4 ) showed the strongest association with lung cancer incidence (population-weighted r = 0.34, p < 0.001). In fully adjusted spatial models, each standard deviation increase in carbon tetrachloride was associated with a 10.6% increase in lung cancer incidence in women and 10.4% in men, and with a 6.5% and 7.6% increase in lung cancer mortality, respectively. In stratified analyses, associations between CCl 4 and lung cancer incidence were larger in lower-smoking counties (10–12% per SD) than in higher-smoking counties (5–6% per SD), with similar patterns by sex. Conclusions: CCl 4 , a legacy industrial solvent with ongoing emissions, was the most predictive air toxin associated with population-level lung cancer incidence, showing larger adjusted associations than PM 2.5 or radon. Although effects were not sex-specific, incidence increases were greatest in lower-smoking communities, suggesting a greater relative contribution of environmental exposures. Percent change in lung cancer incidence and mortality per 1 standard deviation increase in covariates. Variable Women – Incidence (% per 1-SD) Men – Incidence (% per 1-SD) Women – Mortality (% per 1-SD) Men – Mortality (% per 1-SD) Current Smoking (Women) 6.7 (5.9, 7.6) 7.0 (6.2, 7.9) 7.3 (6.3, 8.3) 8.3 (7.4, 9.3) Former Smoking (Women) 4.6 (3.8, 5.3) 1.7 (1.0, 2.5) 5.0 (4.2, 6.0) 1.1 (0.3, 1.9) Current Smoking (Men) 5.0 (4.2, 6.0) 6.9 (6.1, 7.8) 7.4 (6.3, 8.3) 8.5 (7.6, 9.5) Former Smoking (Men) 4.0 (3.1, 4.9) 3.3 (2.4, 4.1) 4.9 (3.9, 5.9) 3.9 (3.0, 4.8) PM 2.5 0.0 (−0.7, 0.7) 0.3 (−0.4, 1.0) 0.9 (0.1, 1.6) 1.3 (0.5, 2.0) Radon 0.9 (−0.2, 2.0) 1.8 (0.7, 2.8) 1.1 (0.0, 2.3) 1.9 (0.7, 3.0) Carbon Tetrachloride (CCl 4 ) 10.6 (9.1, 12.2) 10.4 (8.9, 12.0) 6.5 (5.1, 7.8) 7.6 (6.2, 9.0) Counties in model (n) 2,170 2,238 2,042 2,182

Trends in end-of-life immunotherapy use in metastatic head and neck squamous cell carcinoma: A National Cancer Database analysis.

6035 Background: Aggressive systemic cancer treatment near the end of life (EOL) rarely benefits patients and is an established marker of low-quality healthcare. While EOL chemotherapy use has substantially declined over time, EOL immunotherapy administration has increased in the era of immune checkpoint inhibitors (ICIs). For metastatic head and neck squamous cell carcinoma (mHNSCC), a high-burden disease with rapidly expanding approvals, ICIs have emerged as a compelling mainstay of treatment. However, these expansions may have increased nonbeneficial ICI use among end-stage patients, contributing to quality impacts like decreased hospice enrollment and high financial burden. Given recent evolutions in head and neck cancer care, we conducted a retrospective cohort study to examine temporal trends and factors associated with EOL immunotherapy initiation in mHNSCC. Methods: Patients diagnosed with mHNSCC who received first-course immunotherapy between 2016-2022 were identified in the National Cancer Database. EOL-initiated immunotherapy was defined as initiation within 1 month of death. Two-sample t- or χ² testing was used for comparison of means and proportions, respectively, between EOL and non-EOL immunotherapy initiation groups. Multivariable logistic regression with a priori covariate selection was used to identify factors associated with EOL immunotherapy initiation. Sensitivity analyses were conducted with 2 and 3-month EOL thresholds. Results: Among 8806 included patients, 29.3% received immunotherapy, rising from 17.7% in 2016 to 40.9% in 2022 following first-line FDA ICI approvals. By 2021, EOL-initiated immunotherapy occurred among 6.7%, 13.0%, and 16.4% of treated patients at 1-, 2-, and 3-month EOL thresholds, with possible upward trends after 2019 (2021 vs 2019, 1-month EOL, p=0.114; 2-month EOL, p<0.05, χ² test). In regression analysis, predictors of one-month EOL initiation included female sex (odds ratio [OR]=2.09, 95% CI=1.33–3.27), disadvantaged insurance status (Medicaid/other governmental OR=2.27, 95% CI=1.18–4.35; uninsured/unknown OR=5.09, 95% CI=2.33–11.12), high metastatic burden (≥3 sites OR=8.77, 95% CI=2.94–26.12), and surgical treatment (OR=2.12, 95% CI=1.19–3.79). Protective factors included academic setting (OR=0.60, 95% CI=0.40–0.90), oropharyngeal primary site (OR=0.54, 95% CI=0.32–0.92), and concurrent radiotherapy (OR=0.53, 95% CI=0.35–0.79) or chemotherapy (OR=0.48, 95% CI=0.31–0.73). Conclusions: EOL-initiated immunotherapy occurs among a small but notable proportion of mHNSCC patients and is associated with various indicators of clinical and demographic vulnerability. As ICI use expands, our findings underscore the importance of optimizing patient selection, EOL treatment guidelines, and system-level practices to ensure judicious use of immunotherapy in terminal settings.