Browse Articles

Impact of land use changes on ecosystem services provision in grasslands: a case study from Slovakia

Correction: The necessity of multi-parameter normalization in cyanobacterial research: A case study of the PsbU in Synechocystis sp. PCC 6803 using CRISPRi

Prognosis and management of DCIS with/without microinvasion: Retrospective analysis from SEER and CSCO databases.

e12615 Background: The prognosis and management of patients with ductal carcinoma in situ (DCIS) with microinvasion (DCISM) remain controversial. Methods: We analyzed the outcomes of patients with DCIS or DCISM from the Surveillance, Epidemiology, and End Results (SEER) and the Chinese Society of Clinical Oncology (CSCO) database. Results: Microinvasion was associated with comedo type, human epidermal growth factor receptor-2 (HER2) overexpression, and estrogen receptor (ER) or progesterone receptor (PR) negative status (all P < 0.005). Despite these differences, no statistically significant disparities were observed in prognosis. SEER data showed that breast-conserving surgery (BCS) with radiotherapy was related with improved breast cancer-specific survival (BCSS) (hazard ratio [HR] = 0.06, P = 0.0147) in DCISM patients, as well as overall survival (OS) in both DCIS (HR = 0.42, P = 0.0025) and DCISM patients (HR = 0.26, P = 0.0002). CSCO data indicated BCS with radiotherapy tends to improve disease-free survival (DFS) compared with mastectomy (HR = 0.06, P = 0.053). Chemotherapy was associated with worsened DFS in DCIS (HR = 1.91, P = 0.007), while endocrine therapy improved DFS in hormone receptor (HR)–positive DCIS (HR = 0.46, P = 0.013) in the CSCO database. Conclusions: Although DCISM presents with more aggressive pathology, its survival outcomes are comparable to DCIS. In this study, BCS with radiotherapy was associated with more favorable survival outcomes than mastectomy, regardless of the presence of microinvasion. Chemotherapy was associated with poorer disease-free survival in DCISM.

Role expansion of advanced practice providers over 5 years at Hawai'i's NCI Community Oncology Research Program.

9041 Background: Advanced Practice Providers (APPs), including Nurse Practitioners and Physician Associates, are key members of the oncology team but historically have not been utilized to their full potential in cancer clinical trials. In alignment with NCI policy and guideline changes in 2020 & 2021, the University of Hawaiʻi Cancer Center & Hawaii NCI Community Oncology Research Program (NCORP) began formally engaging their APPs to maximize clinical trial efforts. The objectives of the current project were to measure the impact of the APP role expansion and identify factors contributing to enhancement of APP role in cancer clinical trials. Methods: Data were gathered from the clinical trial management system analyzing APP contributions annually from 2021-2025, including the number of unique APP accruals (enrolling or referring), APPs serving as enrolling/referring investigators, APPs serving as site principal investigator, APPs reviewing trials for feasibility and scientific merit, and trials led by APPs. Informal interviews were conducted to identify the means of APP engagement. Results: From 2021 through 2025 the annual number of patients enrolled or referred to trials by APPs increased from 28 to 103, APPs who accrued patients to trials increased from 4 to 13, APPs serving as site PIs increased from 1 to 6, APPs reviewing trials for feasibility and scientific merit increased from 4 to 6, and trials being led by APPs increased from 13 to 30. In 2025, among trials that allowed APP accrual (symptom management and cancer care delivery), APPs accounted for 51% of this site's total accrual. Factors contributing to APP role in cancer clinical trials were identified as APP leadership and engagement, formal and informal mentorship, and APP educational opportunities. Conclusions: APPs can significantly contribute to cancer clinical trials in terms of accrual and leadership as evidenced by these results. This project illuminates potential avenues for expanding APP roles in clinical research. This group will engage APPs on neighbor islands and Guam with an ultimate goal of increasing clinical trial access for underserved populations who reside on these islands.

Axi-cel vs. tisa-cel vs. liso-cel in R/R DLBCL: Meta-analysis of the efficacy-safety trade-off.

e22002 Background: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies have improved outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Direct comparisons between approved products—axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—remain limited, complicating evidence-based selection in clinical practice. Methods: We performed a PRISMA-compliant systematic review and meta-analysis of randomized clinical trials and real-world studies (through March 2025) evaluating long-term efficacy and safety of commercially available CD19 CAR-T therapies in adults with R/R DLBCL. PubMed, Embase, Cochrane Library, and conference abstracts were searched. Pooled estimates were calculated using random-effects models. Results: Twenty-five studies (4,067 patients; median follow-up 24.6 months) were included. The pooled overall response rate (ORR) was 74% (95% CI, 69–79%), with a complete response (CR) rate of 52% (95% CI, 43–60%). Axi-cel showed the highest ORR (77%; 95% CI, 72–81%) and CR rate (47%; 95% CI, 45–50%). Pooled 1-year progression-free survival (PFS) was 43% (95% CI, 37–49%), and 1-year overall survival (OS) was 66% (95% CI, 59–73%). Safety profiles differed significantly: axi-cel was associated with the highest incidence of immune effector cell-associated neurotoxicity syndrome (ICANS; 34%), while liso-cel had the lowest (9%; 95% CI, 6–13%). Rates of cytokine release syndrome were comparable across products. Conclusions: All approved CD19 CAR-T therapies provide meaningful clinical benefit in R/R DLBCL, but with distinct efficacy–toxicity profiles. These findings support a personalized approach to product selection, integrating patient comorbidities, disease aggressiveness, and institutional experience. Pooled efficacy outcomes of CD19 CAR-T therapies. Outcome Axi-cel (95% CI) Tisa-cel (95% CI) Liso-cel (95% CI) Overall Pooled (95% CI) Overall response rate (ORR), % 77% [72–81] 54% [45–64] 74% [68–79] 74% [69–79] Complete response (CR), % 47% [45–50] 42% [38–46] 49% [46–51] 52% [43–60] 1-year PFS, % 45% [42–47] 28% [25–32] 26% [23–28] 43% [37–49] 1-year OS, % 65%[63–68] 56%[51–60] 55%[52–58] 66%[59–73] CI, confidence interval; ORR, overall response rate; CR, complete response; PFS, progression-free survival; OS, overall survival. Interpretation: The overall pooled estimates (right column) represent a weighted average across all included studies and patient populations. The superior ORR/CR with axi-cel and the favorable safety profile of liso-cel (see main text) underscore the need for treatment personalization.

Hepatic arterial infusion chemotherapy plus either toripalimab or sorafenib as first-line therapy for non–high-risk, locally advanced hepatocellular carcinoma: A non-comparative, randomized phase 2 trial.

4115 Background: A combination of locoregional therapy such as hepatic arterial infusion chemotherapy (HAIC) with anti-angiogenic agents and immune checkpoint inhibitors (ICIs), has demonstrated significant antitumor activity in advanced hepatocellular carcinoma (HCC), while inevitably increasing the incidence of adverse events (AEs). Given the clinical rationale for exploring treatment de-escalation in non-high-risk, locally advanced HCC, this study was designed to provide prospective evidence for the combination of HAIC and toripalimab, which had suggested encouraging antitumor activity and safety previously. Methods: This single-center, non-comparative, randomized phase II study (NCT04135690) recruited locally advanced HCC participants without high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of 50% of the liver). Participants were randomly assigned at a 1:1 ratio to receive FOLFOX-HAIC plus either toripalimab (240mg intravenously, TorHAIC) or sorafenib (400mg orally twice daily, SoraHAIC) per 3 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. Results: From February 4, 2020, to December 17, 2021, 72 participants were randomly assigned to receive TorHAIC (n = 36) or SoraHAIC (n = 36). The mean tumor diameter was 9.9 cm. Vp1-2 and Vp3 portal vein tumor thrombosis were present in 46 (63.9%) and 26 (36.1%) participants, respectively. The 6-month PFS rate was 63.9% in the TorHAIC group and 61.1% in the SoraHAIC group. After a median follow-up of 45.2 months, the median overall survival was 20.9 months in the TorHAIC group and 16.4 months in the SoraHAIC group, while the median PFS was 9.1 and 7.2 months, respectively. The objective response rate per RECIST v1.1 was 52.8% (n = 19) in the TorHAIC group, whereas 47.2% (n = 17) in the SorHAIC group. The median duration of response was 9.8 months in the TorHAIC group and 6.8 months in the SorHAIC group. There were 12 participants (33.3%) who developed grade 3-4 AEs in the TorHAIC group and 16 participants (44.4%) in the SoraHAIC group. Serious AEs were reported in two participants in the TorHAIC group (laryngeal edema due to oxaliplatin allergy and thrombocytopenia) and five participants in the SoraHAIC group (impaired myeloid function [n = 3], renal impairment, and upper gastrointestinal bleeding). Conclusions: Our study suggested that the TorHAIC regimen had a favorable safety and efficacy profile in patients with non-high-risk, locally advanced HCC. However, these findings warrant validation in a phase III trial. Clinical trial information: NCT04135690 .

First-line real-world outcomes of atezolizumab- and pembrolizumab-based regimens in non-squamous non–small-cell lung cancer.

e20591 Background: Direct prospective comparisons of first-line treatment options for advanced non-squamous non–small-cell lung cancer (NSCLC) are lacking. This study evaluated whether real-world clinical data could provide insight into potential differences in effectiveness between two widely applied first-line regimens in the Russian Federation: atezolizumab combined with bevacizumab, carboplatin, and paclitaxel (ABCP) and pembrolizumab combined with pemetrexed and carboplatin (PPC). Methods: A retrospective, single-center analysis was conducted in adult patients with histologically or cytologically confirmed locally advanced, metastatic, or recurrent non-squamous NSCLC. Patients received ABCP or PPC as part of routine clinical care. Progression-free survival (PFS) was analyzed using Kaplan–Meier methodology, with adjustment for baseline imbalances performed via inverse probability of treatment weighting (IPTW). Results: Overall, 189 patients were analyzed (PPC, n = 113; ABCP, n = 76), with a median follow-up of 14.1 months. Prior to IPTW adjustment, median PFS was 9.0 months in the PPC group and 8.1 months in the ABCP group (HR 1.12; 95% CI 0.81–1.55; p = 0.50). Following weighting, PFS outcomes remained comparable between groups (9.2 and 8.8 months), respectively (HR 1.15; 95% CI 0.83–1.61; p = 0.40). Rates of objective response and disease control did not differ significantly (81.3% vs 82.6%; p = 0.70). Subgroup analyses revealed no meaningful interaction between treatment effect and baseline characteristics. In contrast, economic evaluation demonstrated a higher mean annual treatment cost associated with ABCP, exceeding that of PPC by 25% (cost ratio 1.25; 95% CI 1.10–1.43; p = 0.0007). Conclusions: In a real-world retrospective cohort, ABCP and PPC showed similar effectiveness with respect to PFS and tumor response in advanced non-squamous NSCLC. These findings support individualized first-line regimen selection based on patient-specific clinical and molecular considerations rather than expected efficacy differences. Prospective randomized studies are warranted to validate these results.

Real-world effectiveness and safety of first-line pembrolizumab plus chemotherapy in patients aged ≥65 years with metastatic triple-negative breast cancer.

1124 Background: Patients aged ≥65 years constitute a substantial proportion of individuals with metastatic triple-negative breast cancer (mTNBC), but remain underrepresented in clinical trials due to comorbidities and concerns regarding treatment tolerability. While pembrolizumab combined with chemotherapy (P+C) has been established as a standard first-line treatment for mTNBC with a combined positive score ≥10, real-world evidence on its safety and effectiveness in older patients remains limited. Methods: This multicenter observational real-world study (RWS), CEBCC-101, retrospectively analyzed clinical data from 178 female patients with mTNBC treated with P+C in routine clinical practice. Patients were stratified according to age at treatment initiation (<65 vs. ≥65 years). Baseline characteristics, treatment modifications (including dose reductions and treatment delays), adverse events (AEs; graded according to CTCAE v5.0) and clinical outcomes were assessed. Clinical endpoints included progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) evaluated according to RECIST 1.1. Survival outcomes were estimated using the Kaplan–Meier method and compared between age groups using the log-rank test. Results: Among 178 patients, 57 (32.0%) were aged ≥65 years. Median age in the older cohort was 72.4 years (mean 72.3 ± 4.7). Patients ≥65 years had a significantly higher prevalence of relevant comorbidities compared with younger patients (71.9% vs. 39.7%; p<0.001) and more frequently presented with visceral metastases (78.9% vs. 61.2%; p=0.029), driven primarily by a higher incidence of lung metastases (59.7% vs. 42.2%; p=0.043). Rates of chemotherapy dose reductions at treatment initiation or during therapy, treatment delays due to AEs and treatment discontinuation due to toxicity were comparable between age groups. ORR did not differ significantly between patients ≥65 and <65 years (52.6% vs. 55.4%; p=0.767). Median PFS was 9.1 months (mo) in patients ≥65 years versus 8.3 mo in younger patients (p=0.594). Median OS was 22.1 mo and 19.5 mo, respectively (p=0.985). The incidence of grade ≥2 AEs, including pulmonary, neurological, dermatological events and fatigue was similar across age groups. Conclusions: In this RWS, patients aged ≥65 years with mTNBC treated with first-line P+C achieved clinical outcomes and safety profiles comparable to those of younger patients, despite a higher burden of comorbidities and more frequent visceral disease. These findings suggest that chronological age alone should not be a limiting factor for immunochemotherapy and underscore the importance of treatment decisions based on clinical fitness. Broader incorporation of geriatric assessment into routine oncology practice may further optimize patient selection and outcomes.

Neurological immune-related adverse events and overall survival in patients with advanced solid tumors treated with immune checkpoint inhibitors in a global real-world analysis.

11165 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced malignancies, and many immune-related adverse events have been associated with improved treatment outcomes. Neurological immune-related adverse events, however, are uncommon, often severe, and poorly characterized in large real-world populations. Whether the development of neurological toxicity during ICI therapy is associated with long-term survival remains unclear. We examined the relationship between neurological immune-related adverse events and overall survival in a large real-world cohort of patients treated with ICIs. Methods: We performed a retrospective cohort study using data from the TriNetX Global Collaborative Network. Adult patients with advanced solid tumors treated with immune checkpoint inhibitors, including pembrolizumab, nivolumab, ipilimumab, atezolizumab, or durvalumab, were identified. Patients who developed neurological immune-related adverse events (such as encephalitis, meningitis, Guillain–Barré syndrome, myasthenia gravis, or immune-mediated polyneuropathy) within six months of treatment initiation were compared with patients who did not experience neurological toxicity. One-to-one propensity score matching was used to balance age, sex, race, ethnicity, and major medical comorbidities. Overall survival was assessed in the matched cohorts. Results: After matching, 9,744 patients were included (4,872 per cohort) with well-balanced baseline characteristics. Patients who developed neurological immune-related adverse events experienced significantly worse overall survival compared with matched controls. Median overall survival was 473 days in the neurological toxicity cohort versus 1,083 days among patients without neurological events (p < 0.001). Development of neurological immune-related adverse events was associated with a 57% higher risk of death (hazard ratio 1.57; 95% CI, 1.48–1.67). At five years, survival probability was 30.9% in the neurological toxicity group compared with 41.7% in the control group. Conclusions: In this large real-world analysis, neurological immune-related adverse events were associated with substantially worse overall survival in patients treated with immune checkpoint inhibitors. In contrast to other immune-related toxicities that may reflect effective immune activation, neurological complications appear to confer significant morbidity and mortality that outweigh potential treatment benefit. These findings highlight the need for early recognition, multidisciplinary management, and careful risk–benefit assessment when neurological toxicity develops during immunotherapy.

Targeting the delta opioid receptor (DOR) on myeloid immunosuppressive cells: Novel therapeutic approach to hematological malignancies.

e14566 Background: Despite recent progress in the treatment options for hematological malignancies, there remains significant unmet need in some forms of blood cancer such as relapsed/refractory acute myeloid leukemia. Tumor immunosuppression, which remains a major obstacle to cancer immunotherapy, is mainly driven in the tumor microenvironment by myeloid cells including tumor-associated macrophages and myeloid-derived suppressive cells (MDSCs) who play pivotal roles in dampening anti-tumor immune response and promoting tumor progression. Thus, targeting these myeloid cells represents a promising approach to improve cancer immunotherapy. Endogenous and exogenous opioids who interact with specific G-protein coupled surface receptors (MOR, DOR and KOR), have been studied extensively in the context of pain signaling and gastrointestinal functions. However, their role in modulating immunity is still poorly understood. We recently reported that DORs are highly expressed in MDSCs and macrophages and play functional roles in modulating the activity of these myeloid cells. Based on these findings, we initiated a discovery program to identify novel DOR antagonists for use as immunomodulatory agents in hematological cancers. Methods: From our medicinal chemistry campaign, several potent and selective DOR antagonists were identified, including the lead molecule HURA-101. The DOR antagonist potency and DOR/MOR selectivity of the library compounds were assessed in the cyclic AMP functional assays in human DOR or MOR-expressing CHO cells. Results: In the in vitro opioid functional assays, HURA-101 displayed sub-nanomolar potency as DOR antagonist and excellent DOR/MOR selectivity [DOR IC 50 = 0.61 nM; MOR IC 50 > 100,000 nM]. As part of the immunological models supporting the DOR program, we established a human-derived M2a macrophage assay (M2a derived from THP-1 cells using known differentiation/polarization protocol). Importantly, the polarization of THP-1-derived M0 macrophages to the M2a phenotype resulted in a significant increase in DOR surface expression. This result is in line with previous experiments conducted using mouse-derived macrophages and demonstrating that DOR expression is higher in M2 versus M0 phenotypes. Using the THP-1 macrophage assay, the novel DOR antagonists were tested for their ability to modulate expression of macrophage markers and secretion of signaling molecules. Conclusions: To further investigate the role of DOR in modulating immune functions, we initiated a drug discovery program to identify novel DOR antagonists targeting hematological malignancies. The medicinal chemistry campaign led to the discovery of novel potent and selective DOR antagonists. The characterization of selected compounds including the lead molecule HURA-101 across pharmacological and immunological assays will be presented.

A randomized phase II trial of folate receptor alpha peptide vaccine in early-stage triple-negative breast cancer.

536 Background: Folate receptor alpha (FRα) is overexpressed in ~80% of triple-negative breast cancers (TNBC). We previously demonstrated that patients (pts) with breast cancer naturally mount immune responses to FRα. In prior Phase I and II studies, a GM-CSF-adjuvanted FRα peptide vaccine (FRPV) was safe and induced durable FRα-specific T-cell immunity in 83–90% of pts with breast and ovarian cancer. Methods: Eligible pts were women ≥18 years with TNBC (ER/PR ≤10%) with 1+ of the following: stage ≥T1c disease, node-positivity, or residual disease after neoadjuvant chemotherapy. Pts were randomized 2:1 to receive FRPV or placebo (GM-CSF alone) every 28 days for cycles 2-7 and then every six months for 7 booster doses, with cycle 1 consisting of cyclophosphamide 50mg orally twice daily for days 1-7 and 15-21 (in both arms). Randomization was stratified by chemotherapy setting (adjuvant only vs neoadjuvant) and stage (I/II vs III). FRα expression was evaluated by immunohistochemistry. The study was designed to detect (at 30 months after the last pt enrolled) a disease-free survival (DFS) difference of 14% assuming a 3.5-year DFS rate of 70% in the control group and with 78% power. Results: 280 pts were enrolled (median age 52). The majority had stage I or II tumors (n = 219, 78%). There were numerically more node-positive tumors in the vaccine arm, 78 (41%) vs 27 (32%), p = 0.15. Median follow-up was 3.5 years, and 33 (FRPV: 25, placebo: 8) DFS events were observed; 3.5-year DFS rate was 88% with FRPV and 90% with placebo (HR 1.42, 95% CI 0.64–3.15; p = 0.39). Overall survival (OS) also did not differ by arm (HR 2.48, 95% CI 0.55–11.20; p = 0.22). Among node-positive pts (n = 105), DFS did not differ between arms (HR 0.95, 95% CI 0.34–2.66; p = 0.92). However, a numerical DFS event rate improvement (14% for vaccine vs. 26% for placebo) was observed in 61 patients with stage III disease (HR 0.51, 95% CI 0.16–1.68; p = 0.26). DFS did not differ by chemotherapy setting or by receipt of anthracycline, capecitabine, and/or an immune checkpoint inhibitor. FRPV was well tolerated, with predominantly grade 1–2 adverse events (AEs) and no vaccine-related grade ≥4 AEs. FRα expression was available from tumor in 230 pts, with 72% expressing > 0. Overall, DFS was not significantly associated with FRα expression (0 vs > 0; HR 0.55, 95% CI 0.21–1.44; p = 0.21), and no significant differences in DFS by FRα expression were observed between treatment arms. Conclusions: FRPV following oral cyclophosphamide was safe, with no vaccine-related high-grade AEs. While no significant improvement in DFS or OS was observed overall, a numeric trend toward improved DFS was observed in pts with stage III TNBC. This finding is hypothesis-generating and supports further evaluation of FRα-targeted vaccination in higher-risk TNBC. Immune correlative analyses are ongoing to better define vaccine immunogenicity and its relationship to clinical outcomes. Clinical trial information: W81XWH-15-1-0293.

Cell-free DNA nucleosome and genomic signatures as predictors of outcomes with radium-223 in metastatic castration-resistant prostate cancer.

5039 Background: Radium-223 (Ra-223) is a bone-seeking alpha emitter that induces double-stranded DNA breaks. Previous studies have shown Ra-223 can prolong survival of men with mCRPC with symptomatic bone metastases and no visceral metastases. However, clinical outcomes are heterogeneous, and predictive biomarkers for lack of benefit or progression with visceral disease are lacking. We evaluated whether genomic and epigenetic features derived from cell-free DNA (cfDNA) could identify tumor characteristics associated with favorable or unfavorable outcomes with Ra-223 therapy. Methods: Pre-treatment plasma cfDNA was analyzed from 137 mCRPC patients who received Ra-223. Ultra-low pass and deep whole genome sequencing were performed. Tumor fraction and copy number alterations were estimated using ichorCNA. Transcription factor (TF) activity was derived by nucleosome profiling of cfDNA fragments around transcription starts sites (TSS) and TF binding sites using the tools Griffin and TritonNP. Genomic and epigenetic features were associated with clinical outcomes including completion of six Ra-223 cycles, overall survival, and development of new nodal, visceral, or liver metastases. A multimodal binary classifier integrating copy number variation and TF activity was constructed using LASSO feature selection and XGBoost with repeated, nested 5-fold cross-validation. External validation was performed using independent cohorts of mCRPC patients treated with docetaxel (n=46) or other agents (n=142) for the prediction of new metastatic involvement. Results: Higher pre-treatment tumor fraction and TF activity at specific loci including HIF3A, ZNF770, and PRDM6 were associated with adverse outcomes. A binary classifier predicting completion of Ra-223 demonstrated strong discrimination in cross-validation, with similar performance for prediction of liver metastasis progression. External validation in independent cohorts demonstrated moderate discrimination, supporting generalizability across treatment contexts. Conclusions: Our findings demonstrate that analysis of cfDNA-derived genomic and epigenomic features can identify biologically relevant tumor characteristics associated with benefit from Ra-223 in mCRPC. These findings support the development of minimally invasive biomarkers to refine patient selection and risk stratification. Our ongoing analyses look to integrate mutations, amplifications, and deletions in key disease-related genes to further explore tumor genotype-phenotype associations with Ra-223 outcomes.

Association of survival benefit with treatment at academic cancer programs in older adults with PTCL: A National Cancer Database analysis.

e19075 Background: Peripheral T cell lymphoma (PTCL) is an aggressive mature T cell neoplasm associated with poor prognosis and limited therapeutic options. It predominantly affects older adults and is frequently diagnosed at advanced stage. Outcomes for this disease remain inferior compared with many B cell lymphomas despite advances in contemporary lymphoma care. Evidence guiding optimal management in older adults with PTCL remains limited, in part due to the low representation of this population in prospective clinical studies. Population based and real world analyses have shown that older age, comorbidity burden, and differences in access to specialized lymphoma care are independently associated with inferior outcomes beyond underlying disease characteristics. The impact of treatment facility type on outcomes among older adults with PTCL remains insufficiently defined. Methods: We conducted a retrospective analysis of patients aged ≥75 y diagnosed with PTCL in the US between 2004-2022 using the National Cancer Database. Demographic, socioeconomic, clinical, treatment, and survival characteristics were compared between patients treated at Academic Cancer Programs (ACP) and Community Cancer Programs (CCP). Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between the two cohorts. Variables used for adjustment included age, ethnicity, insurance status, distance from hospital, and Charlson-Deyo comorbidity score. Results: Of 4,533 patients aged ≥75 y with PTCL, 2,402 (53.0%) were treated at ACP and 2,131 (47.0%) at CCP. Patients treated at ACP were slightly younger, with a median age of 80 y compared to 81 y at CCP, p=0.002. Most patients in both groups presented with advanced stage disease. Most patients had Medicare coverage, and comorbidity burden did not differ meaningfully between cohorts. Treatment patterns differed by facility type. Patients treated at ACP were more likely to receive treatment, whereas a substantial proportion of patients treated at CCP had no documented treatment.Time from diagnosis to initiation of systemic therapy was shorter at ACP compared with CCP. On survival analysis, two year OS was 29% at ACP vs 26% at CCP, five year overall survival was 17% vs 14%, and ten year overall survival was 8% vs 6%. OS was significantly higher among patients treated at ACP compared with CCP, p=0.047. Conclusions: Among patients aged ≥75 y with PTCL in this national cohort, treatment at ACP was associated with superior OS compared with CCP. Differences in outcomes by facility type suggest that access to specialized lymphoma expertise may influence survival in this population. These findings support the need for timely referral to academic centers, consideration of transfer of care when appropriate, and greater use of expert consultation and guideline based management for older adults with aggressive T cell lymphomas.

Trends in breast cancer incidence, mortality, and disability-adjusted life years in Europe, 1990-2023: A region- and sex-specific analysis.

e12721 Background: Breast cancer is a major contributor to the cancer burden in Europe, with marked regional and sex-specific variation in incidence, mortality, and disability-adjusted life years (DALYs). This study examines region and sex-specific trends in breast cancer incidence, mortality, and DALYs in Europe from 1990 to 2023. Methods: Breast cancer incidence, mortality, and DALYs were analyzed using Global Burden of Disease estimates from 1990-2023. Data were stratified by sex and European subregions. Data was analyzed using multiple joint point models via linear regression analysis. Age-standardized rates were assessed using log-linear regression to estimate annual percent change (APC) and average annual percent change (AAPC) for the full period, with 95% confidence intervals (CIs). Results: From 1990 to 2023, breast cancer incidence increased across Europe. Incidence rose most in Central Europe (AAPC: +1.78% 95% CI: +1.40 to +2.17) and Western Europe (AAPC: +1.59% 95% CI: +1.05 to +2.13), driven by rapid increases during 1990-2000 Central Europe (APC: +2.22% 95% CI: +1.89 to +2.55); Western Europe (APC: +1.54% 95% CI: +1.12 to +1.96) and slower growth and stabilization during 2001-2023. Eastern Europe showed an early rise 1990-2000 APC: +3.76% 95% CI: +3.21 to +4.31 followed by sustained declines in 2001-2023 (APC: -0.94%, 95% CI: -1.19 to -0.69), yielding an overall decrease (AAPC: -0.84% 95% CI: -1.14 to -0.54). Incidence increases were greater among females, while male incidence rose in Central and Western Europe. In contrast, mortality and DALY rates declined across all subregions, with the largest reductions in Western Europe Mortality (AAPC: -1.63%, 95% CI: -1.71 to -1.56); DALYs (AAPC: -1.74%, 95% CI: -1.81 to -1.66), followed by Eastern Europe Mortality (AAPC: -0.55%, 95% CI: -0.82 to -0.28); DALYs (AAPC: -0.88%, 95% CI: -1.15 to -0.61) and Central Europe Mortality (AAPC: -0.39%, 95% CI: -0.49 to -0.29); DALYs (AAPC: -0.70%, 95% CI: -0.79 to -0.60). Trends were non-linear, with the largest increases in Eastern Europe during 1990-2000 Mortality (APC: +1.65%, 95% CI: +1.05 to +2.25); DALYs (APC: +4.60%, 95% CI: +4.07 to +5.14), alongside smaller increases in Central Europe and stable or declining trends in Western Europe, followed by the steepest declines in Eastern Europe during 2001-2023 Mortality (APC: -1.50%, 95% CI: -1.69 to -1.31); DALYs (APC: -2.45%, 95% CI: -2.59 to -2.32), with more modest declines in Central and Western Europe. Females experienced greater mortality and DALY reductions, whereas male trends were less favorable in some regions. Conclusions: From 1990 to 2023, breast cancer incidence increased across much of Europe, particularly in Central and Western regions and among females, while mortality and DALYs declined. Reductions were greatest in Western Europe, with persistent regional and sex-specific differences in long-term trends.

Utilization trends in CAR T cell therapy and bispecific antibodies among Medicare beneficiaries: A five-year claims analysis (2019-2023).

e19012 Background: T-cell engaging therapies, including chimeric antigen receptor T-cell (CAR T-cell) therapy and many bispecific monoclonal antibodies (BsAbs), have expanded treatment options for those living with relapsed/refractory hematologic malignancies. These therapies offer potential for durable remission, making equitable access a critical concern. Despite clinical advances, significant access gaps remain, and real-world utilization patterns across Medicare coverage types remain understudied. Prior research has largely focused on clinical outcomes, costs, and sociodemographic disparities, with limited examination of utilization differences by Medicare coverage type. With Medicare Advantage (MA) enrollment now exceeding 50% of beneficiaries, understanding access patterns has important policy implications. Methods: We conducted a retrospective analysis of CAR T-cell and BsAb claims among Medicare beneficiaries in the United States. Fee-for-service (FFS) claims were obtained from 100% Research Identifiable Files, and MA data were obtained from 100% Medicare Advantage Encounter Data (2019-2023). Unique beneficiaries receiving CAR T-cell or BsAb therapy were identified using HCPCS and ICD-10-PCS codes for seven CAR T-cell products and nine BsAb products. Clinical trial claims were excluded to focus on commercially purchased therapies. FFS claims were excluded if Medicare was not the primary payer. Annual beneficiary counts were tabulated and compared to underlying FFS/MA enrollment shares. Results: From 2019-2023, unique beneficiaries receiving CAR T-cell therapy increased from 336 to 1,635 (FFS) and 150 to 936 (MA); BsAb beneficiaries increased from 78 to 2,920 (FFS) and 248 to 1,826 (MA). In 2023, FFS beneficiaries accounted for 64% of CAR T-cell recipients and 62% of BsAb recipients, despite representing 49% of Medicare enrollment. FFS beneficiaries were approximately 1.3 times more likely than MA beneficiaries to receive both therapy classes relative to their enrollment shares. Conclusions: While utilization of CAR T-cell and BsAb therapies is growing among Medicare beneficiaries, absolute numbers remain modest, and significant access gaps persist; prior research suggests fewer than 2 in 10 eligible patients receive CAR T-cell therapy. FFS beneficiaries are overrepresented among recipients of both therapy classes relative to their enrollment share. Whether this reflects differences in patient characteristics, prior authorization requirements, ATC network participation, or reimbursement dynamics remains unclear. As MA enrollment continues to grow, ensuring equitable patient access to CAR T-cell and BsAb therapies across coverage types warrants further attention. Future research should adjust for patient and clinical factors to better isolate coverage-related barriers.

Integrative spatial omics to identify determinants of response to neoadjuvant chemo-immunotherapy in triple-negative breast cancer.

e12650 Background: Triple-negative breast cancer (TNBC) demonstrates heterogeneous response to neoadjuvant chemotherapy. Pembrolizumab increases pathologic complete response (pCR) rates, yet the biological features underlying sensitivity or resistance remain unclear. Spatial transcriptomics and single-cell RNA sequencing enable high-resolution profiling of immune and stromal ecosystems after therapy. We analyzed spatially resolved immune, stromal, and transcriptional programs associated with pCR versus non-pCR in TNBC treated with neoadjuvant chemo-immunotherapy. Methods: Pre-treatment biopsies (n = 6) and paired post-treatment specimens (n = 3) from patients receiving chemotherapy plus pembrolizumab underwent spatial transcriptomic analysis and immune deconvolution (ESTIMATE, CIBERSORT). Cell composition, immune activation, stromal states, and differentially expressed genes were compared between pCR and non-pCR tumors. Results: Immune deconvolution of pre-treatment samples (4 pCR, 2 non-pCR) showed that non-pCR tumors had lower ESTIMATE immune and stromal scores. Among post-treatment spatial transcriptomic samples (1 pCR, 2 non-pCR), the pCR tumor demonstrated complete loss of malignant epithelial cells and was dominated by immune and stromal populations with strong type I/II interferon responses, cytotoxic lymphocyte activation, and enhanced antigen-presentation signatures. Enriched populations included CD8⁺ T cells, NK cells, dendritic cells, and plasma cells expressing cytotoxic mediators and immune-checkpoint molecules. In contrast, non-pCR tumors showed reduced immune infiltration and a dense collagen-rich stroma, with upregulation of extracellular matrix genes ( COL1A1 , COL3A1 ). Myeloid antigen-presentation pathways were suppressed, including downregulation of CD74 and ferritin-light-chain–associated metabolic programs, indicating an immunosuppressive, metabolically reprogrammed microenvironment. Fibroblast expansion and matrix-remodeling states were prominent in non-pCR tissue. Conclusions: Effective neoadjuvant chemo-immunotherapy in TNBC is marked by dominant interferon-driven immune activation, high cytotoxic lymphocyte infiltration, and preserved antigen presentation, whereas non-pCR tumors display stromal fibrosis and immune suppression. Spatial and single-cell profiling identifies complementary immune and extracellular matrix signatures that may serve as biomarkers to predict response and guide treatment escalation for patients at risk of non-pCR. Immune deconvulation among 6 pre-treatment samples (4pCR and 2 non-pCR). Immune deconvoluation non-pCR non-pCR pCR pCR pCR pCR Stromal score -1396.66 -454.59 -200.80 1859.89 1510.23 2421.45 Immune score -1620.83 -1054.47 -126.42 2235.97 1901.97 2909.68 ESTIMATE score -3017.49 -1509.06 -327.22 4095.86 3412.21 5331.13

Dexamethasone-free antiemetic prophylaxis with olanzapine in children and adolescents receiving highly emetogenic chemotherapy: A multicenter, phase III non-inferiority randomized trial.

10017 Background: Dexamethasone, with a 5-HT3 receptor antagonist and a neurokinin-1 antagonist, is the guideline-recommended prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in children and adolescents receiving highly emetogenic chemotherapy (HEC), but is associated with clinically relevant toxicities. The role of olanzapine as a dexamethasone-sparing agent for pediatric CINV prophylaxis remains uncertain. Methods: This investigator-initiated, multicenter, open label, phase III randomized non-inferiority (NI) trial (INPHOG-SUPP-22-03) enrolled patients aged 4–18 years receiving single or multi-day HEC. Patients were randomized 1:1 (single chemotherapy cycle) to receive dexamethasone, palonosetron, and fosaprepitant (DEX; standard-of-care) or olanzapine, palonosetron, and fosaprepitant (OLANZ; dexamethasone-free). The primary endpoint was complete response (CR) to vomiting (no vomiting and no rescue anti-emetics) during the overall period (0–120 h after the last chemotherapy dose). A NI margin of −15% was prespecified based on adult dexamethasone-sparing trials. Assuming a control CR rate of 70% from prior pediatric studies, 310 patients provided 80% power at a one-sided α of 0.025, allowing for 5% dropout. Absolute differences in CR rates were analyzed using the Miettinen–Nurminen method; NI was concluded if the lower bound of the 95% confidence interval (CI) was above −15%. Results: Between December 2022 and January 2026, 310 patients were randomized (DEX, n=156; OLANZ, n=154). The per-protocol (PP) population included 299 patients (DEX, n=151; OLANZ, n=148). Median age was 13 years; 62.2% were male, and 56.8% received multi-day HEC. In the PP population, the CR rate for vomiting during the overall period was 56.9% in the DEX arm and 63.5% in the OLANZ arm (absolute difference, 6.6%; 95% CI, −4.5% to 17.7%). Non-inferiority was demonstrated, as the lower 95% CI (−4.5%) was above −15%. Results were consistent in the intention-to-treat population. For secondary endpoints, CR to vomiting during the acute period (0-24 h) was 64.2% vs 68.9%, and during the delayed period (24-120 h) 78.8% vs 79.1%, in the DEX and OLANZ arms, respectively. CR to nausea during the overall period was 54.3% vs 53.4%, during the acute period 59.6% vs 59.5%, and during the delayed period 69.5% vs 68.9%, respectively. Grade ≥2 non-hematologic and hematologic laboratory toxicities were uncommon and similar between arms. Any-grade somnolence was significantly higher with OLANZ than DEX (52.0% vs 25.8%), with all events being ≤ grade 2. Conclusions: A dexamethasone-free antiemetic regimen was non-inferior to standard dexamethasone-based prophylaxis for prevention of vomiting in children and adolescents receiving HEC. These findings support the use of olanzapine as an effective steroid-sparing alternative. Clinical trial information: CTRI/2022/08/045009.

Comprehensive clinicogenomic profiling of mucinous carcinomas of the gastrointestinal tract.

e15205 Background: Mucinous carcinoma (MC) is a rare, aggressive histological subtype of adenocarcinoma that is associated with poor prognosis and peritoneal spread. Molecular features of MC across gastrointestinal (GI) primary sites remain incompletely defined. Utilizing the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) v18.0 and OncoKB annotator, we performed a comprehensive analysis of GI MCs. Methods: The AACR GENIE v18.0 database was used to select GI MC and GI non-MC samples by OncoTree code. Samples were analyzed for clinicogenomic variables including age at sequencing, sex, and oncogenic molecular alterations by OncoKB classification (somatic mutations, structural variants, copy number alterations), which were further annotated by therapeutic level of evidence (Levels 1-4). Samples were considered to have a potentially actionable alteration if there was ≥1 Level 1-3B alteration. Two-way models regression evaluated main effects of primary site and mucinous status and their interaction. Benjamini-Hochberg correction controlled false discovery rate, with q < 0.05 considered significant. Results: 786 patients with GI MC were analyzed across primary sites (colorectal (CRC) n = 423; appendix n = 346; stomach n = 17) with corresponding non-MC comparators (CRC n = 20,209; appendix n = 576; stomach n = 2082). Age at sequencing and sex varied by primary site (q-site < 0.001), but no difference was observed by mucinous status. There was higher prevalence of potentially actionable alterations in MC compared to their non-MC variants across primary tumor sites (q-mucinous < 0.001). MC exhibited distinctive molecular patterns with enrichment in KRAS and GNAS (q-mucinous < 0.001), and there were significant site-by-mucinous interactions for KRAS , TP53 , SMAD4 , PIK3CA (q-interaction < 0.05), supporting site-specific drivers in MC biology. Conclusions: To our knowledge, this study represents the largest molecular analysis of MC across the GI tract, revealing distinctive molecular alteration patterns. These findings underscore site-specific genomic patterns and motivate future studies to prioritize therapeutic strategies. Clinical Variable/ Alteration MC CRC Non-MC CRC MC appendix Non-MC appendix MC stomach Non-MC stomach q-value (mucinous) q-value (primary site) q-value (interaction) Age, median (IQR) 61 (49-70) 59 (49-69) 58 (49-67) 58 (50-66) 62 (57-67) 63 (53-72) 0.42 <0.001 0.56 Female (%) 46.3 44.5 53.8 54.9 47.1 40.2 0.82 <0.001 0.82 Potentially actionable alteration (%) 47 40.2 45.7 34.4 52.9 40.6 <0.001 0.025 0.56 KRAS (%) 52.2 40.0 70.5 36.3 5.9 12.8 <0.001 <0.001 <0.001 TP53 (%) 40.9 63.6 22.0 29.5 41.2 48.8 <0.001 <0.001 <0.001 APC (%) 45.2 58.3 5.8 9.5 17.6 8.9 <0.001 <0.001 0.30 GNAS (%) 13.5 2.4 44.5 14.1 5.9 3.9 <0.001 <0.001 0.26 SMAD4 (%) 23.4 23.8 8.4 18.1 11.8 9.2 0.037 <0.001 0.0083 PIK3CA (%) 23.4 18.5 5.5 7.5 0 10.6 0.14 <0.001 0.026

Multivariate survival analysis and prevalence disparities in spindle cell carcinoma: A SEERStat-based retrospective study.

e21569 Background: Spindle cell carcinoma (SpCC) is a rare and aggressive variant of squamous cell carcinoma. It is often a biphasic tumor with both epithelial and mesenchymal components. It is characterized by the presence of elongated “spindle-shaped” cells. The purpose of this study is to determine the racial and gender disparities and survival trends in patients with spindle cell carcinoma. Methods: Total 2661 cases of SpCC were collected from SEER Plus Database, 17 Registries, Nov 2024 Sub (2000-2022), using the ICD Code 8032/3. A multivariate Cox proportional hazards regression model was used to examine the effects of independent variables including age [continuous variable], sex [reference = males], race [ref = Caucasians], year of diagnosis [continuous variable], stage [ref = localized], median household income inflation adjusted to 2023 [ref = < 100K], and treatment including surgery, chemotherapy (CTX), XRT [ref = no Tx utilized, respectively] on the survival. Dependent variables were survival (months) and an event (1 = death, 0 = censored). All analysis was conducted using GraphPad Prism 10.6.1. Results: Of the dataset, 51.8% were females. Racial distribution was: 73% Caucasians and 27% non-Caucasians races. The median age of diagnosis was 71 years. The overall median of survival (MoS) was 10 months, with a 1-year OS of 46.2% (CI 95%, 44.3%-48.1%) and 5-year OS of 26.9% (CI 95%, 25.2%-28.7%) The overall Cox proportional hazards model for multivariate analysis was statistically significant (p < 0.05). The results of the model are shown in Table 1. Conclusions: Our analysis revealed that for every 1-year increase in age, the hazard of death increased by 2.8%. Moreover, the female gender had 18% decreased risk of death compared to males. Regional spread was associated with 1.96-fold while distant stage with 3.5-fold increased risk of death compared to localized disease. Use of surgery was associated with 41% lower risk, CTX with 21% lower risk, and XRT with 13% reduced risk of death compared to no surgery, no CTX or no XRT, respectively. Higher income [ > 100K] showed 11% decline in hazard of death compared to income less than 100K. No significant association was found between race and income with survival. Further analysis highlighting the use of targeted therapy for SpCC is warranted. Variables Hazard Ratio (HR) 95% CI P value Age 1.028 1.025 - 1.032 <0.0001* Gender[female] 0.8239 0.755 - 0.898 <0.0001* YOD 0.99 0.986 - 1.001 0.0709 Race[non-Caucasians] 0.997 0.899 - 1.104 0.9529 Stage[regional] 1.957 1.726 - 2.222 <0.0001* Stage[distant] 3.51 3.034 – 4.064 <0.0001* Surgery[yes] 0.5913 0.534 – 0.6552 <0.0001* Chemotherapy[yes] 0.7944 0.7138 – 0.883 <0.0001* XRT[yes] 0.87 0.79 – 0.957 0.0040* Income[>100K] 0.8947 0.8021 – 0.9957 0.0413* *statistically significant.

Machine learning–based identification of patients at risk for early infectious complications after CAR-T in multiple myeloma.

e19518 Background: Infections occur in 50–70% of Multiple Myeloma(MM) patients after CAR T therapy, with the highest risk in the first few months during the period of profound and recurrent cytopenias. Although the incidence and timing of infections have been well characterized, prospective identification of patients at highest risk remains a challenge. Existing risk models have focused on adverse events across heterogeneous B-cell malignancies, and no MM-specific, infection-focused tool exists for prospective risk stratification. We developed a MM-specific, Day 0, clinically based machine-learning model to enrich for early (≤60 day) severe infection risk after anti BCMA CAR T. Methods: We conducted a retrospective analysis of 51 MM patients treated with CAR T (both ide-cel and cilta-cel) at our institution between September 2024 - May 2025. The primary assessment was grade ≥3 infection within 60 days of infusion. Baseline clinical variables used to develop a Day 0 infection risk model were age, ECOG status, comorbidity burden, and high-risk myeloma features. An elastic-net logistic regression approach was employed to estimate the probability of early severe infection. This modeling framework allows multiple correlated clinical variables to contribute to risk estimation while applying regularization to reduce overfitting in modestly sized datasets. Model performance was evaluated with an emphasis on clinical risk enrichment rather than individual level prediction, including assessment of discrimination, calibration, and observed infection rates across strata of predicted risk. Results: Fourteen patients (27%) developed grade ≥3 infections within 60 days, with most occurring within the first 30 days. Greater than 50% required readmissions post initial CAR T discharge. Among grade ≥3 infections, 65% were viral and 36% bacterial, challenging the assumption that early events are predominantly bacterial. The model demonstrated modest discrimination (apparent AUC 0.67) with meaningful risk stratification. When patients were grouped into tertiles of predicted risk, observed 60-day infection rates increased stepwise from 18% in the low-risk group to 30% in the intermediate-risk and 35% in the high-risk group. Calibration was generally reasonable, with underestimation of risk among the highest-risk patients. Conclusions: Using readily available Day 0 clinical variables, the study demonstrates proof of concept that early severe infection risk after CAR T therapy can be stratified in real world practice. While not intended for precise individual prediction, it provides a clinically actionable risk enrichment tool to inform post infusion management. The model may help identify patients who could benefit from intensified early surveillance or a lower threshold for admission and may support risk-based design of future infection prevention trials after CAR T therapy.