Browse Articles

End-of-life care quality indicators in advanced cancer patients at a Brazilian tertiary hospital.

e24083 Background: Quality of end-of-life care in advanced cancer emphasizes timely palliative integration, symptom control, family engagement, advance directives, and avoidance of chemotherapy near death or intensive support. Intensive treatments or chemotherapy near death often reflect low-value care and missed palliative opportunities. This study aimed to evaluate the quality of EOL care among adult oncology inpatients who experienced in-hospital mortality at a private hospital in Brazil. Methods: This retrospective study at a private Brasília tertiary hospital expands prior analysis (N=197, Jan 2023 to Feb 2025) to full 2023-2025 (N=235), describing metrics and patient factors. Consists of a review of electronic health records of all adult oncology inpatients who experienced in-hospital mortality between January 2023 and December 2025 (N = 235) at a private hospital in Brazil. Data included demographics, cancer types, ECOG/PPS at admission, palliative follow-up, last-30-day chemotherapy, directives, symptom management, family conferences, artificial support, treatment intent. Data were analyzed descriptively, and associations between categorical variables were evaluated using the chi-square test. (p<0.05). Results: The median age of the patients was 73 years (range: 25-99), with females accounting for 52% of the sample. Poor functional status was common, with 55% presenting an ECOG performance status of 3-4. The most prevalent primary malignancies were pancreatic (13%), lung (10%), and colorectal cancer (9%). The main reasons for hospital admission were infection (46%) and cancer-related symptoms (40%). Almost all patients received palliative care support, with palliative team involvement documented in 99.6% of cases (234/235). Patients with last-30-day chemo were younger (median 68 vs 75 years; p=0.02), had higher ECOG (3.8 vs 3.2; p=0.03), lower PPS (40% vs 60%; p<0.01), and frequent pancreas/glioblastoma primaries. Conclusions: In this cohort, palliative care was integrated for almost all patients and was associated with effective symptom control and strong family involvement. Despite this, a substantial proportion received late chemotherapy, highlighting ongoing challenges in aligning end-of-life care with patient needs and clinical prognostic factors. Key indicators. Indicator n (%) Advance directives 82 (35) Symptom control 230 (98) Family conference 219 (93) Artificial support 42 (18) Palliative intent 183 (78) Chemo last 30 days 66 (28)

Quantifying financial toxicity from cancer care travel in a geographically isolated U.S. health system.

e13543 Background: Geographic isolation and limited availability of subspecialty oncology services can force patients to travel long distances for cancer care, disrupting continuity and contributing to financial toxicity. Hawaiʻi, the most geographically isolated health system in the United States, provides a natural model for examining how structural constraints drive out-of-state (OOS) cancer care utilization and costs—challenges shared by many rural and medically underserved regions nationwide. Objectives: To quantify OOS cancer care spending in Hawaiʻi from 2021–2023 and to identify cancer types and services most associated with OOS treatment, informing oncology capacity planning in geographically constrained settings. Methods: We conducted a retrospective analysis of administrative claims from commercially insured adults with cancer in Hawaiʻi, identified using Episode Treatment Groups (ETGs). For each year (2021–2023), we quantified the paid amounts for cancer-related services delivered outside Hawaiʻi and identified patients who received any OOS care. For 2023, we summarized member-level utilization by tumor type, including proportions of patients with OOS costs and high-cost OOS episodes (≥$100K). Spending and utilization patterns were examined by cancer type and service category. Results: Total OOS cancer spending increased from $58M in 2021 to $94M in 2022, before declining to $79M in 2023. In 2023, over 3,000 commercially insured cancer patients incurred OOS costs. The highest OOS utilization was observed in breast (953/6,199; 15% of patients, 13% of total costs), pulmonary (241/839; 29%, 9%), leukemia (144/594; 24%, 48%), multiple myeloma (65/249; 26%, 28% ), lymphoma (141/897; 16%, 21%) and central nervous system tumors (46/195; 23%, 27%). OOS utilization was most strongly associated with systemic therapy delivery, specialized diagnostics, and complex surgical care. Conclusions: OOS cancer care represents a substantial and persistent source of economic toxicity for patients and payers in geographically isolated systems and reflects structural gaps in oncology capacity in the State of Hawaiʻi. For instance, hematological malignancies and CNS tumor patients departing Hawaiʻi suggest limited in-state availability of subspecialty expertise, advanced diagnostics, and complex systemic therapies. Although the data are derived from Hawaiʻi, these patterns are broadly applicable to other regions facing geographic and oncology workforce constraints. Targeted expansion of high-impact subspecialty services, earlier multidisciplinary care planning, integration of tele-oncology, and expansion of the clinical trial portfolio may reduce avoidable travel, improve continuity of care, and support more equitable cancer treatment delivery.

Antidepressant use and overall survival in ICI treated pan-cancer patients: A real-world analysis.

e23395 Background: Antidepressants are frequently prescribed to cancer patients, yet their impact on outcomes during immune checkpoint inhibitor (ICI) therapy is unclear. We evaluated the association between SSRIs, SNRIs, and bupropion use and overall survival (OS) in ICI treated patients. Methods: This retrospective real world study used the TriNetX Research Network to identify ICI treated adults with solid tumors, grouped by antidepressant exposure and depression diagnosis, with propensity score matching and overall survival analyzed using Kaplan-Meier (KM) and Cox models, including agent-specific comparisons using sertraline (Ser) as the reference. Results: In the patients treated with ICI, SSRI/SNRI use was associated with inferior OS compared with no SSRI/SNRI exposure, with higher mortality (42.4 vs 33.5%), and worse KM survival (p < 0.0001). In patients with a diagnosis of depression, using Ser as reference, fluoxetine, escitalopram, citalopram, paroxetine, venlafaxine, and duloxetine showed no significant differences in OS. In contrast, bupropion demonstrated improved OS compared with Ser, with lower mortality (39.5 vs 47.2%) and reduced risk of death (p = 0.0019). However, when compared with no antidepressant exposure, bupropion was associated with higher mortality (38.6 vs 33.3%), and inferior KM survival (p = 0.0002). Conclusions: In ICI treated patients, SSRI/SNRI use was associated with inferior OS compared with no antidepressant exposure, potentially reflecting confounding by depression and comorbidity burden; in agent specific analyses, other SSRIs/SNRIs did not differ from Ser, while bupropion showed improved OS versus Ser, but remained inferior to no antidepressant use, underscoring the need for prospective validation. OS by antidepressant use in ICI treated pancancer population. Groups N per group Mean Follow up (days) Deaths (%) Risk Ratio(95% CI) KM Median survival (days) p for KM Hazard Ratio (95% CI) No AntidepressantvsAntidepressant 27032 741vs766 34vs42 0.79(0.774-0.809) 2045vs1156 0.0001 0.80(0.78-0.824) ServsFluoxetine 954 761vs684 44vs45 0.96(0.781-1.122) 953vs958 0.29 0.93(0.812-1.063) ServsEscitalopram 1946 757vs781 44vs44 0.99(0.921-1.062) 1020vs1156 0.82 1.01(0.92-1.112) ServsCitalopram 971 738vs788 45vs48 0.92(0.843-1.021) 957vs903 0.53 0.96(0.841-1.093) ServsEscitalopram 1946 757vs781 44vs44 0.99(0.921-1.062) 1020vs1156 0.82 1.01(0.92-1.112) ServsParoxetine 496 708vs758 48vs49 0.98(0.86-1.111) 809vs903 0.79 1.03(0.857-1.228) ServsVenlafaxine 804 746vs795 43vs47 0.93(0.833-1.032) 957vs868 0.51 0.95(0.823-1.101) ServsDuloxetine 1735 790vs758 47vs45 1.04(0.966-1.117) 963vs976 0.76 1.02(0.92-1.121) BupropionvsSer 982 756vs759 40vs47 0.84(0.756-0.928) 1314vs876 0.001 0.81(0.705-0.924) No AntidepressantvsBupropion 2208 751vs707 33vs39 0.86(0.798-0.935) 1972vs1262 0.0002 0.83(0.753-0.918)

Burden of breast cancer attributable to secondhand smoke in North American women: A GBD 2023 analysis (1990-2023).

e22568 Background: Breast cancer remains a leading cause of cancer-related morbidity and mortality among women. Secondhand smoke is a preventable environmental carcinogen, yet its contribution to the breast cancer burden in North America has not been well explored. This study assesses long-term trends in breast cancer burden attributable to secondhand smoke among North American women. Methods: Data from the Global Burden of Disease (GBD) 2023 study were used to evaluate the burden of breast cancer attributable to secondhand smoke among North American women from 1990-2023. Age-standardized death rates and disability-adjusted life years (DALYs) were the measures analyzed. Eligible countries were identified according to the United Nations classification. Temporal trends over the study period were assessed using Joinpoint regression analysis to calculate annual percent change (APC) and average annual percent change (AAPC), with corresponding 95% confidence intervals. Results: From 1990-2023, breast cancer death rates attributable to secondhand smoke among North American women declined significantly overall (AAPC -3.32%). Substantial reductions were observed in Canada (AAPC -4.07%) and the United States (AAPC -3.23%). Declining trends were also seen in Mexico, Panama, Costa Rica, and Greenland. In contrast, mortality increased in El Salvador (AAPC 1.25%), Guatemala (1.18%), and Nicaragua (0.57%). Over the same period, age-standardized DALYs showed a similar overall decline across North America (AAPC -3.37%), with marked reductions in Canada (-4.01%) and the United States (-3.30%). However, age-standardized DALYs increased in El Salvador (1.10%), Guatemala (1.06%), and Nicaragua (0.81%). Conclusions: This GBD 2023 analysis demonstrates a substantial decline in breast cancer mortality and DALYs attributable to secondhand smoke among North American women over the past three decades, with the most pronounced reductions observed in Canada and the United States. These trends likely reflect the cumulative impact of comprehensive smoke-free legislation, declining household tobacco exposure, improved public awareness, and advances in breast cancer screening and treatment. In contrast, the rising burden observed in El Salvador, Guatemala, and Nicaragua highlights persistent regional disparities within North America. These increases may be driven by weaker enforcement of smoke-free policies, continued indoor biomass and tobacco exposure, limited access to early detection, and constrained oncology care infrastructure. The divergence in trends underscores the unequal benefits of tobacco control and cancer prevention strategies across the continent. Strengthening smoke-free environments, particularly in domestic settings, alongside targeted public health interventions in high-burden countries, may further reduce preventable breast cancer morbidity and mortality.

First-line tislelizumab plus chemoradiotherapy for patients with advanced biliary tract cancer: A prospective, biomolecular exploratory, phase II trial.

4125 Background: Advanced biliary tract cancer (BTC) characterized by a poor prognosis, and the combination of immunotherapy with conventional chemoradiotherapy offers a promising therapeutic approach. Methods: This phase II study evaluated the efficacy and safety of tislelizumab (an anti-PD-1 antibody) in combination with chemoradiotherapy as a first-line treatment for advanced BTC. The primary endpoints were objective response rate (ORR) and R0 resection rate, and the secondary endpoints included median progression-free survival (mPFS), median overall survival (mOS), and Disease Control Rate (DCR). Biomarker analyses assessed CA19-9 dynamics and immune cell subsets. Results: Among 28 patients, the ORR was 57% (16/28), with a conversion rate of 14% (4/28) and a 100% R0 resection rate (4/4). The median PFS was 14 months and the median OS was 19 months. The regimen exhibited a manageable safety profile, with grade 3 adverse events occurring in 21% (6/28) of patients (2 with drug-induced liver injury and 4 with myelosuppression). No grade 4 events were observed. Reduced CA19-9 levels were significantly correlated with improved OS (p = 0.022) and PFS (p = 0.002). Immunohistochemistry analysis revealed differential expression of CD4, CD103, and PD-1 between responders and non-responders. Notably, high expression of CD103 + CD8 + tissue-resident memory T (TRM) cells and CD103 + CD8 + PD-1 + TRM cells was associated with significantly improved OS. Conclusions: In conclusion, the combination of tislelizumab with chemoradiotherapy demonstrates promising efficacy and acceptable safety in advanced BTC, with CD103 + CD8 + TRM cells identified as a potential predictive biomarker. Clinical trial information: ChiCTR2300070425.

Effect of IL7 on ImmTAC-mediated killing by T cells in vitro and T-cell fitness in patients.

2662 Background: A blood T cell fitness (TCF) signature, reflecting properties of naïve and stem cell memory T cells, was strongly associated with clinical benefit from tebentafusp (gp100 × CD3) and brenetafusp (PRAME × CD3) ImmTAC bispecific therapies¹. Here, we assessed whether TCF could be enhanced by IL7, a cytokine that plays a key role in T cell homeostasis and promotes the proliferation and survival of naïve and stem cell memory T cells. Methods: T cell exhaustion was induced in vitro by four weekly ImmTAC stimulations against the Non-Small Cell Lung Cancer (NSCLC) cell line NCIH1755 with or without IL7. Tumor killing, T cell cytokine secretion, and T cell phenotype were assessed using standard methods. Data are given as mean ± SEM; groups were compared using paired t test. IL7R gene expression and TCF (mean expression of TESPA1 , CD28 and GPR183 ) were measured in baseline whole blood from patients with unresectable or metastatic uveal melanoma (mUM) treated with tebentafusp (n=132 NCT02570308) or brenetafusp (N=37 NCT04262466) as previously described 1 . TCF high/low threshold was cut at the median. TCF was also assessed in baseline and on-treatment PBMC from patients with NSCLC and Triple-Negative Breast Cancer (TNBC) (n=15) receiving NTI7, a long acting recombinant human IL7 (rhIL7, NCT03752723, NCT04984811). Results: In vitro, repeated re-direction of T cells by ImmTAC resulted in reduced tumor cell lysis from 46±9% after a single stimulation to 3±1% after 4 weekly stimulations. In contrast, T cells cultured with IL7 retained tumor cell lysis after 4 stimulations (58±2% ImmTAC-redirected cytolysis compared with 3±1% in IL7-untreated T cells, p = 0.02), accompanied by a 14.3-fold increase in IFNγ secretion (p = 0.04). The proportion of naïve/stem cell memory T cells increased in response to IL7 treatment from 37±5% to 57±8% (p=0.009). In mUM patients, gene expression of IL7R strongly correlated with TCF signature in peripheral blood (R = 0.91, p < 0.001). As early as 3 weeks following a single dose of NTI7, TCF increased by ~3-fold in PBMC from NSCLC and TNBC patients. The proportion of TCF high patients increased from 36% at baseline to 93% post NTI7 monotherapy. This increase in TCF signature was sustained for at least 12 weeks. Conclusions: Despite repeated antigen stimulation in vitro, IL7 sustained naïve/memory T cells, enhanced ImmTAC-redirected T cell cytotoxicity and IFNγ production, and reduced T cell exhaustion. A single dose of rhIL7 resulted in a sustained increase in TCF signature and converted patients with low TCF signature into high TCF. These findings support combination with IL7 as a rational strategy to augment T cell fitness and potentially improve efficacy of ImmTAC bispecific T cell therapies. 1) Sacco et al ESMO 2024.

A personalized neoantigen vaccine to reprogram the immune landscape of glioblastoma.

2006 Background: Glioblastoma (GBM) remains uniformly lethal despite standard therapy. An immunosuppressive tumor microenvironment (TME) and limited T cell infiltration pose major barriers to immunotherapy. Personalized neoantigen vaccines offer a strategy to prime tumor-specific T cell responses by targeting patient-specific mutations, driving effector cells into the CNS. Here, we report results from a phase I trial of a personalized neoantigen peptide vaccine combined with pembrolizumab in newly diagnosed GBM. Methods: Patients with newly diagnosed GBM who were not on dexamethasone following gross total resection were enrolled across four cohorts. Up to 20 synthetic long peptides targeting personal neoantigens were selected per patient, and admixed with the adjuvant poly-ICLC (NeoVax). Following radiotherapy, NeoVax was administered subcutaneously as five priming doses followed by two booster doses. MGMT -unmethylated patients (Cohorts 1A-C) received NeoVax plus pembrolizumab without temozolomide (TMZ) and differed by time of pembrolizumab initiation relative to NeoVax priming; MGMT -methylated patients (Cohort 1D) received standard TMZ and pembrolizumab was initiated after NeoVax priming. Immunogenicity was assessed by ex vivo and in vitro IFN-γ ELISpot assays. Single-nucleus/single-cell RNA sequencing and TCR sequencing (snRNA-seq/scTCR-seq) was performed on paired tumor specimens. Results: Of 39 enrolled patients, 37 initiated NeoVax including 35 who completed priming and 2 with ongoing priming. Treatment was well-tolerated with no serious AEs. Median overall survival was 36.9 months for MGMT -methylated patients and 19.0 months for MGMT -unmethylated patients, compared to 25.3 and 16.7 months for propensity score-matched historical controls, respectively. Ex vivo and in vitro neoantigen-specific T cell responses were detected comparably across all cohorts and overall in 65% and 97% of vaccinated patients, respectively. Among all patients, ex vivo immune responders demonstrated improved overall survival compared to non-responders (HR 0.26, 95% CI 0.09-0.77, P = 0.015). Vaccine-reactive clonotypes, defined by in vitro expansion to vaccine peptides, were identified in post-vaccination tumors. snRNA-seq/scTCR-seq revealed increased intratumoral vaccine-specific T effector populations following vaccination. Conclusions: NeoVax generates durable T cell responses that traffic to GBM tumors, with circulating responses associated with improved survival. Ongoing studies are evaluating peripheral clonotype dynamics, remodeling of malignant cell states and the TME, and the spatial distribution of vaccine-reactive clonotypes, which may guide future combinatorial strategies in GBM. Clinical trial information: NCT02287428 .

PMH-001: A first-in-human phase I study of the novel microtubule disruptor CCI-001 in patients with advanced cancer.

e15167 Background: CCI-001 is a thiocolchicine derivative, ßIII tubulin-selective microtubule disruptor being studied in the first in human PMH-001 Phase I trial as monotherapy (dose-escalation, -expansion) and in combination with carboplatin and gemcitabine. Methods: PMH-001 Part 1 was an open-label, single agent dose-escalation study. Objectives were to determine the recommended Phase II dose (RPIID) of IV CCI-001 (primary) and to assess CCI-001 safety, PK profile, and clinical response rate (secondary). Metastatic solid tumour patients were dosed on days (D) D1, 8 and 15 of each 28-day cycle (C) until progression or unacceptable toxicity. PK sampling was on C1D1 and 15, and pre-dose C2D1 to evaluate Cmax, Tmax, AUC and T 1/2 . Dose-escalation was a 3+3 design. Toxicity was evaluated with CTCAE v5.0 criteria, and efficacy by CT imaging (baseline, every 8 weeks) using RECIST 1.1. Results: Part 1 had 6 dose levels: 1.2 mg/m 2 (5 pts), 2.4 mg/m 2 (3 pts), 4.8 mg/m 2 (6 pts), 6.0 mg/m 2 (6 pts), 7.5 mg/m 2 (6 pts), and 6.75 mg/m 2 (6 pts). Of 32 pts (14 male, 18 female) treated, 25 were evaluable for safety, 20 for PK and 23 for response. Of 305 TRAEs, 10 (3.3%) were ≥ Gr 3, with those occurring in ≥ 5% of pts being neutropenia (4 pts). There were 3 DLTs: Gr 3, Gr 4 neutropenia at 4.8, 6 mg/m 2 (related) and 1 death at 7.5 mg/m 2 (cardiac, unrelated). Twelve pts (38%) had a dose interruption, 4 pts (13%) had dose reduction, and 1 pt (3.1%) was discontinued (unrelated TEAE). Two pts (6.2%) withdrew (personal decision; toxicity). The MTD of 7.5 mg/m 2 was due to fatigue (non-DLT, intolerable Gr 2), and RPIID was assigned at 6.75mg/m 2 . Of response-evaluable pts, the overall response rate (ORR) was 1 of 23 or 4.3% (partial response, squamous cell carcinoma of the lung, 7.5 mg/m 2 , who previously failed paclitaxel). Twelve pts (52.2%) showed stable disease (SD) as Best Overall Response (BOR). Median number of weeks on trial (n = 23) was 8.0 (range 8 to 40 weeks), with 6 pts on therapy for ≥ 6 cycles (months). Median progression-free survival (PFS) was 8.0 weeks (n = 18 after censoring). One patient (6.75 mg/m 2 , lung cancer) went off trial at C10 D15 ( > 2 dose reductions), but was still on treatment at C12D1 at 4.8 mg/m 2 . CCI-001 AUCinf and Cmax increased in a dose-dependent manner, with no accumulation between C1D1 and C1D15. No CCI-001 was detected pre-dose C2D1. At 6.75 mg/m 2 , CCI-001 mean C1D1 AUCinf, Cmax and T 1/2 were, respectively, 2080 h*ng/mL, 643 ng/mL and 8.6 h (n = 2). Cl obs and VD obs were, respectively, 6.2 L/h and 77 L. Conclusions: The RPIID of single agent CCI-001 is 6.75 mg/m 2 . CCI-001 was well tolerated at all dose levels tested, with AEs typical for a drug of this class. Peripheral neuropathy was rare (3 Gr 1 AEs, 2 related). The early safety and response data suggest a role for CCI-001 in combination with other anticancer drugs. Clinical trial information: NCT04823897 .

Validation of DiaSurv, an AI-based algorithm for stage II colon cancer risk stratification.

3524 Background: Adjuvant chemotherapy decisions in stage II colon cancer (IIA T3N0; IIB T4aN0; IIC T4bN0) remain challenging, as conventional risk factors poorly predict recurrence. This results in both overtreatment and undertreatment. AI-based analysis of routine H&E slides may enable more accurate risk stratification to guide personalized treatment decisions. Methods: DiaSurv Colon is an AI-powered prognostic tool using a deep neural network to extract in an unsupervised way morphological features from H&E-stained WSI and predict 5-year overall survival (OS). Each patient is assigned an individual survival risk score. The model was trained on the TCGA cohort (n = 463) and previously validated on two external cohorts. In this study, we evaluated its performance on two new independent external cohorts, digitized with two different scanners: CHU Caen (n = 201; 5-y OS 47%, 95%CI 39-53%) and IHP (n = 207; 5-y OS 54%, 95%CI 45-61%). Prognostic accuracy was assessed using concordance index (c-index). Multivariate Cox regression and log-rank tests with hazard ratios (HR) were used to compare DiaSurv Colon performance against conventional clinicopathological factors. Results: On external validation, DiaSurv Colon achieved a c-index of 58 (CHU Caen) and 64 (IHP). The AI-based risk score significantly stratified patients: 5-year OS was 64% (95%CI 50-75%) vs 40% (95%CI 32-48%) for low- vs high-risk groups in CHU Caen (p < 0.01), and 64% (95%CI 52-73%) vs 39% (95%CI 26-51%) in IHP (p < 0.001). The risk score demonstrated strong prognostic value with hazard ratios of 1.29 (95%CI 1.05-1.58, p < 0.01) and 1.57 (95%CI 1.23-2.00, p < 0.001) for CHU Caen and IHP, respectively. Conclusions: DiaSurv Colon demonstrated consistent prognostic performance across independent external cohorts, with robust hazard ratios and concordance indices. This AI-based tool may improve risk stratification in stage II colon cancer and support personalized adjuvant therapy decisions with more confidence.

Trends in Patient-Reported Outcomes Measurement Information System (PROMIS) utilization in oncology research: A scoping review of ClinicalTrials.gov and PubMed (2015-2025).

e23256 Background: PROMIS (Patient-Reported Outcomes Measurement Information System) has seen rapid adoption in clinical research, yet comprehensive trends in oncology-specific utilization over the past decade remain uncharacterized. Analysis of both ClinicalTrials.gov registry and PubMed published literature provides a comprehensive view of PROMIS utilization patterns, capturing both planned and completed research. This scoping review examined annual trends in PROMIS oncology use across ClinicalTrials.gov and PubMed from January 2015 through November 2025. Methods: ClinicalTrials.gov searched for trials and PubMed for studies registered between January 2015 and November 2025 using: (PROMIS OR "Patient-Reported Outcomes Measurement Information System") AND (oncology OR cancer OR malignancy). For ClinicalTrials.gov, data extraction was performed using Python scripts with AI assistance (Claude Opus 4.5, Anthropic), followed by manual validation. For PubMed, records . Extracted variables: year, PROMIS domain(s), cancer type, measure type (short form/CAT/profile), and intended respondent (adult/pediatric/parent-proxy). Results: From 2015 to 2025, annual oncology trial registrations grew from 27 to 154 (5.7-fold), while oncology publications with PROMIS increased from 28 to 191 (6.8-fold). Within clinical trials, the most frequently assessed PROMIS domains were Fatigue (n=192, 19%), Anxiety (n=172, 17%), and Depression (n=162, 16%). The most common cancer types were multiple/general cancer (n=358, 36%), breast cancer (n=258, 26%), and hematologic malignancies (n=106, 11%). Breast cancer-specific trials decreased proportionally (48% to 25%) while multiple/general-cancer studies increased (15% to 37%). Adult trials comprised 89% (n=898), growing from 26 to 137 annually. Pediatric and adolescent trials increased from 1 (2015) to 17 (2025), representing growth from 4% to 11% of oncology PROMIS trials. Conclusions: PROMIS utilization in oncology research has grown substantially over 11 years, with parallel trends observed across trial registrations and published literature. Fatigue, anxiety, and depression remain core assessment domains. Breast cancer-specific trials using PROMIS decreased (48% to 25%) while studies including multiple cancer types increased (15% to 37%).

Correction: Expression of Concern: Signaling Networks Associated with AKT Activation in Non-Small Cell Lung Cancer (NSCLC): New Insights on the Role of Phosphatydil-Inositol-3 kinase

Cryogenic enhancement of phononic four-wave mixing in AlScN/SiC

Surface acoustic wave platforms based on piezoelectric thin-film heterostructures provide sub-wavelength acoustic confinement, making them attractive for compact nonlinear phononic systems with applications including frequency conversion, parametric interactions, and nonlinear signal processing. Here, we investigate guided surface acoustic wave phononic four-wave mixing at gigahertz frequencies in an aluminum scandium nitride (Al0.58Sc0.42N)/4H–silicon carbide heterostructure operated at both room temperature (295 K) and cryogenic temperature (4 K). The 500-nm thick aluminum scandium nitride film supports guided Rayleigh and Sezawa modes with distinct displacement and strain energy density distributions, allowing a direct comparison of mode-dependent nonlinear behavior within the same device. Continuous-wave four-wave mixing measurements reveal an enhancement in the extracted modal nonlinear coefficient at 4 K relative to 295 K for both modes. In addition, the Rayleigh mode exhibits a modal nonlinearity approximately two orders of magnitude larger than that of the Sezawa mode across both temperature regimes. These results demonstrate that phononic four-wave mixing is strongly influenced by temperature, mode confinement, and strain localization while establishing aluminum scandium nitride on silicon carbide heterostructures as a promising platform for engineering enhanced nonlinear phononic interactions for future classical and quantum acoustic on-chip signal processing systems.

Eco-friendly synthesis of Ag/Au bimetallic nanoparticles using Ruta graveolens leaf extract and their catalytic activity for the reduction of 4-nitrophenol

Closed‐loop Recycling of Sulfide Solid Electrolytes from Spent Solid‐State Sodium Batteries

ABSTRACT All‐solid‐state sodium batteries (ASSSBs) are promising for large‐scale energy storage due to sodium abundance and intrinsic safety. However, from a sustainability perspective, the recyclability of solid electrolytes is critical but largely unexplored, as many mature solid electrolytes rely on low‐abundance, high‐cost elements, limiting long‐term scalability. Herein, we firstly report a closed‐loop recycling strategy for Na 3 SbS 4 (NAS) solid electrolytes guided by the DFT calculations, enabling efficient recovery and regeneration from spent all‐solid‐state sodium batteries via a mild dissolution–recrystallization–thermal treatment process. The recycled NAS (R‐NAS) fully preserves the long‐range crystal structure, local coordination environment, and chemical states of the pristine material. The R‐NAS delivers good ionic conductivity, electrochemical stability, reduced polarization, enhanced rate performance, and superior cycling stability comparable to pristine NAS (P‐NAS). This work demonstrates the feasibility and importance of the recycling of high‐performance sulfide solid electrolytes from spent devices without compromising structural integrity or functionality. The proposed recycling strategy offers a generalizable and sustainable pathway for the reutilization of advanced solid electrolytes, contributing to the circular economy of all‐solid‐state battery technologies.

Implementation and analysis of quantum majority rules under noisy conditions

Abstract Quantum voting, inspired by quantum game theory, provides a framework in which the quantum majority rule (QMR) constitution of Bao and Yunger Halpern [Phys. Rev. A 95, 062306 (2017)] violates the quantum analogue of Arrow’s impossibility theorem. We evaluate this QMR constitution analytically on classical profile data and implement its final measurement stage as a quantum circuit, running on both noiseless simulators and noisy IBM quantum hardware to map how realistic noise deforms the resulting societal ranking distribution. For the dephased profiles studied here, the post-processing steps act diagonally in the preference basis, so the ideal distributions underlying QMR’s violation of the quantum analogue of Arrow’s impossibility theorem can be computed classically before any optional quantum circuit sampling. Moderate readout and device noise generally preserve the qualitative behavior of QMR, whereas strong noise can shift the distribution toward different dominant winners or larger top-cycle structures, depending on the profile geometry. We quantify this behavior using winner–agreement rates, Condorcet-winner flip rates, and Jensen–Shannon divergence between societal ranking distributions. In addition to two representative hand-crafted profiles, we perform further robustness checks on randomized Dirichlet-sampled electorates and on cyclic and almost-cyclic near-threshold profiles, showing that the main QMR trends persist beyond the original examples while also revealing a sharp dependence on proximity to cycle-dominated majority structures. Unlike the two benchmark hand-crafted profiles, the randomized Dirichlet ensembles do not in general exhibit near-perfect robustness at very low noise, revealing substantial profile-to-profile sensitivity already near the noiseless limit. In a second, complementary component, we demonstrate an explicitly entanglement-based variant of the QMR constitution that serves as a testbed for multi-voter quantum correlations under noise, which we refer to as the QMR2-inspired variant. There, GHZ-type blocks and separable superpositions over opposite rankings have the same single-voter marginals, while their different correlation structure changes draw rates and variance in small mini-rounds; this effect is fragile under local noise and is washed out in the large-population limited-entanglement setting. Taken together, these two components connect the abstract QMR constitution to concrete implementations on noisy intermediate-scale quantum (NISQ) devices and highlight design considerations for future quantum and quantum-inspired voting protocols.

Minor hemolysin-coregulated proteins (Hcp) form heteromeric complexes and mediate effector secretion in Bacteroidales type VI secretion systems

Participation of older adults (aged ≥65 years) in SWOG cancer clinical trials.

1543 Background: Cancer disproportionately affects older adults. Approximately 60% of cancer diagnoses occur in adults aged 65 and older in the United States. However, disparities persist in participation of older adults in cancer clinical trials. Methods: Using 38 years of data from phase III trials of the SWOG Cancer Research Network between 1985 to 2022, this study examined clinical, socio-demographic, and trial factors associated with participation of older adults (≥65 Years) in cancer clinical trials. Summary statistics were used to describe patient and trial characteristics. To examine factors associated with enrollment of older adults, mixed-effects multivariate logistic regression was performed with the odds of being an older adult (≥65 years) as the dependent variable. Results: A total of 45,670 patients accrued to 64 SWOG phase III trials were included in the analysis. Across all trials, 30.6% participants were aged 65 and older, and 57.8% were female. Participants were predominantly non-Hispanic (96.2%) White (87.4%) and most resided in urban areas (82.4%). Regression analysis results showed that adjusted odds of enrollment as an older adult did not differ statistically significantly by cancer stage or intervention type (targeted therapy, immunotherapy, hormonal therapy, chemotherapy, radiation, or surgery). Compared with breast cancer trials (reference group with the lowest proportion of older adult enrollment), the odds of enrolled participants being older adults were higher in gastrointestinal cancer trials (OR=3.39), lung/thoracic cancer trials (OR=3.24), and genitourinary/prostate cancer trials (OR=6.77). Compared with White participants, Black participants (OR=0.64) and Asian/Pacific Islander (OR=0.64) had lower adjusted odds of being older adults. The odds of being aged ≥65 years were nearly twice as high among non-Hispanic participants compared with Hispanic participants (OR=1.85). Participants from rural areas had higher adjusted odds of being aged ≥65 years than those from urban areas (OR=1.10). No statistically significant differences were observed across Area Deprivation Index (ADI) quartiles. Conclusions: Although some progress has been made in the participation of older adults in cancer clinical trials in the past decades, more work needs to be done to enhance their participation (especially those belonging to underrepresented groups) in cancer clinical trials. Tailored and targeted recruitment efforts are needed to improve participation of diverse older adults in cancer clinical trials.

Dynamics of nectin-4 (N4) expression in urothelial carcinoma (UC): Across disease states.

3131 Background: Enfortumab vedotin (EV), which targets N4, has revolutionized advanced UC management. Despite high prevalence of N4 in UC, the temporal stability of N4 is poorly characterized. Conflicting reports describe both decreased and increased expression in metastatic (met) UC compared to primary tumors raising uncertainty as to whether changes reflect antigen loss or quantitative modulation—an issue central to resistance to EV. Methods: This single-center retrospective study identified pts with met UC who received treatment (trt) with EV. Demographic, clinicopathologic, trt and survival data (from time of met diagnosis) were recorded. N4 expression was evaluated via immunohistochemistry (IHC) (N4 Clone EPR15163-68) H-Score in available primary (TURBT, cystectomy/nephroureterectomy) and met tissue. H-Score was assessed as N4 positive (+) vs negative (neg,-) (>0 vs 0) and ordinally (neg, low <100, medium 100-200, high >200). Concordance between specimen pairs was assessed using percent agreement, McNemar’s test, and weighted Cohen’s kappa. Overall survival (OS) was evaluated via Kaplan–Meier methods and exploratory Cox regression. Results: We identified 141 pts (median age 70; 71% male; primary: bladder (83%), upper tract (15%), synchronous (2.1%), unknown (0.7%). 93% of primary tumors were N4+ (n=44). In matched TURBT-Cystectomy pairs (n=21), binary status was stable (95% agreement), but ordinal concordance was poor (27% agreement, κ= −0.05) and significant antigenic dampening was observed: High N4 expression decreased from 90% at TURBT to 29% at cystectomy, with a reciprocal increase in medium-level expression from 10% to 48% (p<0.001). 89% of met sites (n=27) were N4+. There were no differences in receipt of prior neoadjuvant chemotherapy (NAC) or 1st line trt between met N4+ and N4- groups. In matched cystectomy and metastases pairs (n=11), binary N4 concordance remained high (82% agreement) with poor ordinal concordance (27% agreement, p=0.12). Neither binary nor ordinal metastatic expression, nor changes in H-score over time, were associated with OS. There were no differences in OS in binary met N4+ vs N4- (p=0.82) nor ordinally classified groups (p=0.43). Conclusions: N4 is a stable binary target in UC, maintaining positivity across primary and metastatic sites despite significant quantitative dampening in expression intensity. These findings, although exploratory suggest that tumor evolution and therapeutic resistance may be characterized by dynamic antigen density modulation rather than categorical loss, an interpretation that may help reconcile prior discordant reports of expression changes in metastatic disease. Future studies should evaluate whether the degree of H-score shift (rather than absolute value) correlates with the durability of response to EV as well as the impact of neoadjuvant and subsequent sequential treatments on N4 expression intensity.

Sensitivity detection of colorectal precancerous lesions and cancer by assessing cell-free multimodal chromatin states in plasma.

e15661 Background: Cell-free DNA in blood originates from fragmented chromatin released by dying cells from both healthy and diseased tissues. These fragments carry rich molecular modalities that can reveal pathological alterations in tissues of origin. Design of sensitive technologies capturing the molecular modalities in body fluid should open a new revenue to greatly advance cancer diagnostics. Methods: cf-EpiTracing has been implemented on a Biomek i5 automated workstation to capture genome-wide multiple cell-free histone modifications in human plasma (50-100 μL). A two-round barcoding strategy was used to achieve high throughput, facilitating the parallel processing of 96 samples. Simplified procedures allow efficiently profiling cell-free epigenome in hundreds of samples within 6 h after antibody incubation. XGBoost machine learning models were developed to: classify colorectal cancer (CRC) patients and healthy individuals, and detect early colorectal precancerous lesions (colorectal adenoma, CRA). Results: By integrating multimodal chromatin states with machine learning, cf-EpiTracing enables accurate cancer detection and subtyping. The XGBoost model yielded robust CRC-healthy classification performance in both training (accuracy, 0.976) and independent validation group samples (accuracy, 0.922; Table 1). When applied to CRA detection, the model achieved a detection rate of 77.3%. Additionally, cf-EpiTracing achieved high classification accuracy for both colon and rectal cancer subtypes, in both early-stage (stage I, 66.7%; stage II, 69.2%) and advanced-stage (stage III, 80.0%; stage IV, 100.0%) patients. Conclusions: cf-EpiTracing leverages holistic epigenetic signatures, independently of knowledge for gene transcription, for realizing the noninvasive detection of pathological alterations in target tissues or cell types of origin. Thus, cf-EpiTracing represents a paradigm shift in colorectal diagnostics and may be widely applicable for other cancer types. Performance metrics of CRC detection. Sensitivity Specificity Accuracy Precision Recall F1 score Training dataset(93 healthy + 75 CRC) 0.987 0.968 0.976 0.989 0.968 0.978 Validation dataset(32 healthy + 32 CRC) 0.907 0.938 0.922 0.909 0.938 0.923

Influence of a vertically integrated care system on mortality risks in insured patients by race and ethnicity.

e13559 Background: Vertically integrated health care systems may help reduce racial and ethnic disparities in cancer outcomes through coordinated, comprehensive care. Kaiser Permanente, a vertically integrated healthcare system serving approximately 5 million members in Southern California, provides an opportunity to evaluate whether such a system is associated with improved survival rates among insured patients across racial and ethnic groups. Methods: Data were obtained from the California Cancer Registry and included insured adults diagnosed with invasive cancers in Southern California from January 1, 2015 through December 31, 2021, with follow-up through December 31, 2022. Patients with in situ cancers were excluded. Patients (N = 416,574) were categorized by site of diagnosis: Kaiser Foundation Hospitals (KFH) versus non-KFH hospitals. Mortality rates measured as deaths per 1,000 person-years (d/1000PY) with 95% confidence intervals (95% CI) were calculated by race and ethnicity. Cox proportional hazards models were fit separately within each race/ethnicity group, adjusting for age, sex, socioeconomic status quintile, county, insurance type, and stage at diagnosis were used to evaluate the association between diagnosis site (KFH vs. non-KFH) and overall survival. Results: Overall mortality rates were lower in KFH compared with non-KFH hospitals 87.4 d/1000PY (95% CI: 86.3, 88.4) vs. 103.1 d/1000PY (95% CI 102.4, 103.8). Mortality rates by racial/ethnic group for KFH vs. non-KFH were: White 93.6 d/1000PY (95% CI 92.0, 95.1) vs. 100.7 d/1000PY (95% CI 99.8, 101.7), Black 100.7 d/1000PY (95% CI 97.3, 104.2) vs. 136.3 d/1000PY (95% CI 132.7. 140.0), non-White Hispanic 77.7 d/1000PY (95% CI 75.8, 79.6) vs. 106.8 d/1000PY (95% CI 105.2, 108.3), and Asian 76.8 d/1000PY (95% CI 73.9, 79.7) vs. 99.5 d/1000PY (95% CI 97.4, 101.6). Mortality risks were lower amongst KFH patients after multivariate adjustment (non-KFH, ref): White hazard ratio (HR) 0.88 (95% CI 0.86, 0.89); Black HR 0.78 (95% CI 0.75, 0.82); non-White Hispanic HR 0.78 (95% CI 0.75, 0.82); Asian HR 0.77 (95% CI 0.74, 0.81). Conclusions: These results suggest that vertically integrated healthcare systems are associated with lower mortality risks among patients with cancer and ethnic groups with the greatest benefit observed for non-White patients. After adjustment, White patients in the KFH integrated healthcare system were 12% less likely to die during follow-up, while Black, non-White Hispanic, and Asian patients experienced reductions of 22%, 22%, and 23%, respectively compared to their race/ethnicity group counterparts in non-KFH hospitals.