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Early experience with T-cell receptor cellular therapy in advanced solid malignancies: A multi-center analysis of safety and efficacy.

e14511 Background: T-cell receptor (TCR) therapy, by targeting intracellular antigens, represents a significant expansion of treatment options for solid tumours. We report the safety and preliminary efficacy from our early institutional experience using TCR therapy in a cohort of heavily pretreated patients with advanced solid malignancies. Methods: This multi-centre study included eight patients with advanced solid tumours. The primary endpoint was safety, assessed according to CTCAE v5.0, while secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) evaluated by RECIST v1.1. Survival outcomes were analysed using Kaplan-Meier methodology. Results: The cohort was extensively pretreated, with a median of 4 prior therapy lines (range: 3-5), and all patients had previously receivedimmunotherapy. Engineered TCRs targeted a range of intracellular antigens, including TP53 (n = 6), KRAS (n = 2), and CEA (n = 1). With a median follow-up of 9 months, the ORR was 50% (4/8 patients; 95% CI: 15.7-84.3%), consisting of four partial responses. A promising DCR of 75% was achieved (6/8 patients; 95% CI: 34.9-96.8%), with a median time-to-response of 2.0 months. Median event-free survival was 7 months, and median overall survival was not reached. The treatment was well-tolerated; only one patient (12.5%) experienced a grade 3 cytokine release syndrome, which was successfully managed. No immune-effector cell-associated neurotoxicity syndrome (ICANS) or other grade ≥3 adverse events were observed. Conclusions: In this heavily pretreated population, TCR-T cell therapy demonstrated significant anti-tumour activity and a favourable safetyprofile. These findings underscore the feasibility of this approach and warrant further investigation in larger clinical trials. Parameter Value Patients (N) 8 Median Age (range) 51 (29-67) Sex (Male/Female) 4 / 4 ECOG PS (0/1) 1 / 7 Median Prior Lines (range) 4 (3-5) Prior Immunotherapy 100% TCR Targets (TP53/KRAS/CEA) 6 / 2 / 1 Objective Response Rate (ORR) 50% (95% CI: 15.7-84.3) Disease Control Rate (DCR)Median Time-to-ResponseMedian Event-Free SurvivalMedian Overall SurvivalGrade ≥3 Adverse EventsGrade 3 CRSICANS 75% (95% CI: 34.9-96.8)2.0 months7 monthsNot Reached12.5%12.5% (1/8)0%

Trabectedin with concomitant radiotherapy in resectable retroperitoneal L-sarcoma: A multicenter, prospective, phase I/II trial—A collaborative study by the Spanish (GEIS), Italian (ISG), and French (FSG) groups.

11507 Background: Liposarcoma (LPS) and leiomyosarcoma (LMS) account for most retroperitoneal sarcomas. Despite complete resection, local recurrence remains high, particularly in dedifferentiated LPS (DDLPS). While preoperative radiotherapy (RT) may improve local control, optimal multimodal strategies are undefined. Trabectedin (T) is active in L-sarcomas, with emerging clinical evidence supporting its radiosensitizing properties and its efficacy in combination with RT. A preoperative short course of T with concurrent low-dose RT was investigated in a multicenter, phase I/II trial in patients (pts) with centrally confirmed resectable retroperitoneal L-sarcoma (grade 2-3 DDLPS with >30% dedifferentiated component or grade 2-3 LMS). Methods: Pts received 3 cycles of T in combination with RT (45 Gy in 25 x 1.8 Gy). Phase I followed a 3+3 dose-escalation design with T dose levels 1.5 (0), 1.3 (-1), and 1.1mg/m 2 (-2). Dose-limiting toxicity was any grade ≥3 adverse events (excluding neutropenia <5 days, elevated transaminases without treatment delay, and nausea/vomiting due to inadequate prophylaxis). Phase I primary endpoint was safety and the determination of the recommended Phase II dose (RP2D). Phase II primary endpoint was centrally assessed Choi response. Secondary endpoints included relapse-free survival (RFS; from surgery), progression-free survival (PFS; from first T cycle), overall survival (OS), RECIST and pathological response, and treatment-related toxicity according to CTCAE v5.0. Results: From February 2019 to January 2025, 56 pts, 6 in phase I and 50 in phase II, (M/F: 31/25) with a median age of 61 years (range: 19-75) and a median tumor size of 17 cm (range: 12-30) were enrolled. 51 pts had grade 2-3 DDLPS, and 5 pts had grade 2-3 LMS. A T dose of 1.5 mg/m 2 was the RP2D. Per-protocol therapy was completed in 47 pts (84%); discontinuations were due to local progression (N=1), toxicity (N=6), or refusal (N=2). The most common grade 3/4 toxicities were neutropenia (21.4%), leukopenia (8.9%), fatigue (8.9%), and increased ALT, febrile neutropenia, and thrombocytopenia (7.1% each). 51 pts (91%) underwent surgery, with 96% achieving complete resection. According to the central review, Choi (N=45) showed 12 PR (26.7%) and 33 SD (73.3%). RECIST 1.1 (N=53): PR 1 (2%), SD 51 (96%), PD 1 (2%). At a median follow-up of 40 months (95% CI, 36-43), from the start of T (N=53), 3-year PFS was 70% (95 CI, 56-83) and 3-year OS was 85% (95 CI, 75-95). Conclusions: Preoperative concurrent T and RT was feasible and safe for resectable retroperitoneal L-sarcomas, yielding density responses in over 25% of pts and promising survival outcomes. A phase III trial is warranted to compare this regimen against RT alone. Clinical trial information: NCT02275286 .

Multiplexed immunohistochemistry (mIHC) analysis and clinical outcomes of nelmastobart in combination with trifluridine/tipiracil and bevacizumab in patients with refractory colorectal cancer (phase 1b/2).

3602 Background: Colorectal cancer (CRC) patients who are refractory or intolerant to oxaliplatin- and irinotecan-based regimens face limited treatment options and poor prognoses. BTN1A1, a novel immune checkpoint protein involved in tumor progression and immune evasion, presents a potential therapeutic target. Nelmastobart, a first-in-class anti-BTN1A1 monoclonal antibody, is being evaluated in combination with trifluridine/tipiracil and bevacizumab in the Phase 1b/2 STCUBE-003 trial (NCT06873763). This study employs multiplexed immunohistochemistry (mIHC) to characterize the tumor microenvironment (TME) and identify biomarkers predictive of therapeutic response in CRC patients. Methods: Tumor tissues from 120 CRC patients were prescreened for BTN1A1 expression via immunohistochemistry (IHC). A total of 61 patients with a tumor proportion score (TPS) ≥50 were enrolled in the Phase 2 study. Pathologists used the TPS to guide patient selection, with TPS ≥50 as the inclusion criterion. Selected samples were analyzed using mIHC (Opal and CellDIVE), utilizing a 20-protein panel relevant to cancer immunology. Protein co-expression and the spatial distribution of immune and malignant cells were evaluated to assess tumor-immune interactions. Results: Among 120 tumor samples analyzed by IHC, 78 (65%) exhibited TPS ≥50. Sixteen patients (13%) showed no expression (TPS 0), and 26 (21.6%) had low to medium expression (1 ≤ TPS ≤ 49). This expression profile aligns with previous CRC studies (STCUBE-001 and STCUBE-IIT-001). In the initial efficacy evaluation of 39 patients with TPS ≥50, 2 (4.8%) achieved a partial response (PR), 27 (69.2%) showed stable disease (SD), and 8 (20.5%) had progressive disease (PD). High BTN1A1 expression was significantly associated with a higher clinical response rate. mIHC analysis further revealed that BTN1A1 expression correlated with Ki-67, SLFN11, and YAP1, as well as distinct patterns of CD8⁺ T-cell infiltration. Conclusions: BTN1A1 is consistently and highly expressed in refractory CRC (median TPS 50). mIHC analysis confirms that BTN1A1 is closely integrated with key immune checkpoints and tumor markers within the TME. Initial clinical results, which show disease control in the majority of patients, particularly within the TPS ≥50 population, support the utility of BTN1A1 as a predictive biomarker for Nelmastobart combination therapy. These findings justify the ongoing biomarker-driven Phase 2 portion of the STCUBE-003 trial. Clinical trial information: NCT06873763 .

Telehealth use at the end of life among Medicare decedents with cancers.

e23120 Background: Telehealth use has surged since the COVID-19 pandemic. For individuals with cancer approaching end-of-life (EOL) facing high symptom burden, declining mobility, and increasing reliance on caregivers, telehealth may enhance access to specialty and palliative care services. National evidence comparing EOL telehealth use between cancer and non-cancer populations remains limited. Methods: We conducted a retrospective, population-based cohort study of telehealth use using 100% Traditional Medicare (TM) and Medicare Advantage (MA) claims. We included Medicare beneficiaries died in 2019-2023 with continuous TM or MA enrollment in the 12 months preceding death. Patients with cancer were identified by 1 inpatient or 2 outpatient visits with cancer diagnosis codes in the last year of life. Telehealth use in the last year of life was identified using procedure codes and modifiers and classified into synchronous patient–provider (audio-only and audio–video), asynchronous, and remote physiologic or therapeutic monitoring (RPM/RTM) encounters. Telehealth use, overall and by service type, was compared between Medicare decedents with and without cancer; multivariable logistic regression examined patient characteristics associated with telehealth use after COVID-19 onset. Results: Among a total of 10,767,407 Medicare decedents, average age was 81.56, with 51.8% female, 9.7% Non-Hispanic Black, 2.3% Hispanic, and 33.1% with cancer diagnosis. Telehealth use among decedents with cancer increased from 2.7% to 47.8% in 2019-2023, peaking in 2021 (70.0%), which was persistently higher than those without cancer (2.4% to 34.4% in 2019-2023). Synchronous video encounters (1.2% to 41.2%) were most common, followed by synchronous audio only encounters (1.6% to 20.9%) in 2019-2023. RTM/RPM was limited but increased from 0.1% to 2.0% in 2019-2023. Decedents with cancer were consistently more likely to use all telehealth modalities than those without cancer. In adjusted analysis, older (85+ vs. 66-74 years: -6.10 percentage points [ppts]), Non-Hispanic Black (vs. Non-Hispanic White: -3.27 ppts), and beneficiaries in counties with a higher social vulnerability index (Q4 vs. Q1: -0.92 ppts, p-values<.001) were less likely to use telehealth. More comorbidities (14.70 ppts), multiple hospitalizations in the prior year (5.18 ppts), and counties with better broadband internet access (80%+ households with 25+ Mbps internet connection vs. ≤40%: 13.98 ppts, p-values<.001) were associated with higher likelihood of telehealth use. Conclusions: EOL telehealth use differs meaningfully between cancer and non-cancer decedents, which may reflect greater care intensity and more frequent clinical contact. Telehealth use was lower among older, racial and ethnic minority beneficiaries, and those living in more socially vulnerable areas, and higher among patients with greater medical complexity and better broadband access.

Treatment strategies and survival outcomes in hepatic epithelioid hemangioendothelioma: A systematic review.

e16239 Background: The hepatic epithelioid hemangioendothelioma, or HEHE, is a very rare type of blood vessel cancer that shows different symptoms and does not have a standard treatment plan. Emerging non-surgical therapy and prognostic indicators are still not well described, although liver transplantation (LT) and liver resection (LR) are frequently pursued. This systematic review looks at the results and survival rates of different groups of HEHE patients from published studies to help doctors make better treatment choices based on evidence. Methods: The purpose of this study was to conduct a systematic review of 18 studies that included 1,105 patients who had histologically confirmed HEHE. These studies covered both surgical and non-surgical treatment modalities. Data were collected on demographics, treatment approaches, overall survival (OS), disease-free survival (DFS), recurrence rates, and the duration of patient follow-up. Only studies that included at least five patients and data that could be extracted from the outcomes were considered for inclusion. Results: 18 studies, which included 1105 patients diagnosed with HEHE, were analyzed. The median age was 46 years, and approximately 60–65% of the patients were female. The treatments included liver resection (LR, LT) and non-surgical methods like TACE and sirolimus. Surgical interventions were associated with improved survival rates. The OS rates for liver resection were 96%, 86%, and 88% after one, three, and five years, respectively. Conversely, liver transplantation exhibited OS rates of 91%, 73–80%, and 73–75% at the same intervals. Non-surgical management, in contrast, presented more heterogeneous outcomes, with five-year OS rates fluctuating between 37% and 63%. 10 years after treatment, the OS rates were low for all groups, with liver transplantation showing a 35% survival rate, liver resection at 20%, and non-surgical treatments at 23%. 5-year disease-free survival ranged from 37.4% to 60.1%. Worse survival rates were linked to having bone metastases, a larger tumor size, older age, and lung involvement. It is important to note that patients receiving surgical interventions exhibited significantly improved long-term outcomes when contrasted with those managed non-surgically (5-year OS: 88% versus 49%). The median follow-up duration was 39 months across the studies, ranging from 8 to 76.6 months. Conclusions: Surgical intervention improves HEHE survival, especially without bone metastases. Liver resection had high OS rates, whereas LT was still a possibility for some patients. Nonsurgical therapy had mixed results, suggesting that patients require customized treatment. Bone metastases, age ≥60, and symptom load were negative prognostic factors. This rare malignancy requires prospective registries and global data sharing to improve therapeutic decision-making.

A DFT insight into the Ta-doped GaX nanotubes (where X=N and P) to develop a non-invasive breast cancer sensing material

Seta‐Inspired Mechano‐Intelligent Janus Bandage with Coordinated Adhesion–Contraction for Minimizing Scarring

ABSTRACT While advances have been made in mechano‐active and gecko‐inspired wound dressings, achieving dynamically coordinated adhesion–contraction coupling within a single‐material, stimulus‐free system with quantitatively programmable contractile output remains an unmet challenge. Here, we engineer bioinspired mechano‐intelligent Janus bandages (MIBs) with dynamically coordinated adhesion–contraction for effective wound healing. The MIBs are fabricated through micromolding of poly(lactide–co–propylene glycol–co–lactide) dimethacrylates (PmLnD), featuring an interior surface with a gecko‐mimicking wedged structure. Upon application, the MIBs recapitulate the gecko locomotion principle to achieve precise control of contractile forces with dynamically coordinated adhesion–contraction. The simply pre‐strained MIB can precisely program its intrinsic contractile force, while adhesion strength proportionally responds to the contractile force through enhanced van der Waals interactions and interfacial friction. This coordinated mechanism promotes healing in rat and porcine full‐thickness skin defect models by accelerating re‐epithelialization and enhancing angiogenesis. Mechanistically, the MIBs reduce focal adhesion kinase (FAK) expression, thereby regulating downstream pathways related to wound healing progression, including nuclear factor kappa B (NF‐κB), Wnt, and transforming growth factor‐beta (TGF‐β) pathways, enabling scar‐attenuated wound healing. We envision that this Janus design, which integrates strain‐programmable contraction with reversible gecko‐inspired adhesion, offers a useful addition to current mechanobiological strategies for wound management and soft tissue repair.

A phase 1/2 study of REGN5668, a MUC16×CD28 costimulatory bispecific antibody, in combination with other targeted therapies, in patients with recurrent ovarian or endometrial cancer: Trial in progress update.

TPS5639 Background: REGN5668 and ubamatamab are immunoglobulin G4-based bispecific antibodies that bridge mucin 16 (MUC16)+ tumor cells to T-cell–expressed cluster of differentiation (CD)28 and CD3, respectively, to stimulate T-cell cytotoxicity. Cemiplimab (anti–programmed cell death-1 [PD-1]) and fianlimab (anti-lymphocyte activation gene 3 [LAG-3]) are monoclonal antibodies that target inhibitory T-cell immune checkpoints. This first-in-human, multicenter, Phase 1/2 trial (NCT04590326) will assess safety, tolerability, pharmacokinetics (PK), and antitumor activity of REGN5668 + cemiplimab ± fianlimab (Module 1) or ubamatamab (Module 2) in patients with platinum-resistant recurrent ovarian cancer (OC) or endometrial cancer (EC). In Module 1, REGN5668 dose escalation is complete (n=58), demonstrating early clinical activity and only 1 dose-limiting toxicity, a treatment delay of >7 days due to Grade 1 dry eye. Here we present details of additional dose escalation and expansion modules currently enrolling patients. Methods: Module 1 dose expansion will evaluate REGN5668 + cemiplimab ± fianlimab in OC and EC cohorts. In the OC cohort, patients will receive REGN5668 + cemiplimab + fianlimab, with an initial 12-patient safety lead-in. In the EC cohort, patients will receive REGN5668 + cemiplimab; an additional EC cohort may be added to evaluate REGN5668 + cemiplimab + fianlimab. Each cohort will follow a Simon two-stage design. In stage 1, 20 patients will be enrolled; if there are ≥3 objective responses, stage 2 will proceed with enrollment of ≤50 patients. In Module 2, dose escalation will evaluate patients with OC receiving escalating doses of REGN5668 + ubamatamab using a Bayesian optimal interval design. Patients may also receive sarilumab to mitigate the risk of cytokine release syndrome. Key OC cohort eligibility criteria include histologically confirmed diagnosis of advanced epithelial OC (except carcinosarcoma), ≥1 prior line of platinum-based systemic therapy, and disease relapse or progression during most recent therapy. Key EC cohort eligibility criteria include histologically confirmed diagnosis of EC with disease recurrence or progression after anti–PD-1 therapy and platinum-based chemotherapy, ≤4 prior lines of systemic therapy, ≥30 days since anti–PD-1 therapy administration, and ≥25% of tumor cells that are MUC16+. Primary endpoints are safety and PK in dose escalation, and objective response rate (ORR) in dose expansion. Secondary endpoints include ORR (Module 2 dose escalation), safety and PK (Module 1 dose expansion), further efficacy outcomes, and immunogenicity (all cohorts). Module 1 dose expansion has opened, with the first two patients enrolled. In Module 2, dose escalation of REGN5668 has progressed through multiple dose levels; enrollment is ongoing. Clinical trial information: NCT04590326 .

Machine learning–based multi-omics analysis to identify the role of MAN1C1 in pancreatic cancer and its clinical significance as a drug target.

e16475 Background: Exploring genes related to glycosylation modification, particularly the role of MAN1C1 in PDAC, contributes to the development of new therapeutic strategies. Methods: Single-Cell Analysis: Analyzed cell types and their glycosylation levels in the PDAC TME using scRNA-seq data (GSE212966). Dimensionality reduction and clustering were performed, combined with cell type annotation to identify tumor cell populations. GO, KEGG, and ssGSEA enrichment analyses were conducted to elucidate cellular functional states. Scoring & Interaction: Evaluated scores of glycosylation modification-related genes, with a special focus on fibroblasts. Established correlations between Cancer-Associated Fibroblasts (CAFs), CD4+ T cells, and tumor-associated macrophages to interpret potential intercellular communication patterns. Trajectory Analysis: Pseudotime analysis was used to explore tumor progression trajectories and describe potential malignant evolutionary laws of cells. Model Construction: Based on TCGA-PAAD transcriptomics (training set) and GSE28735 (validation set), 9 machine learning algorithms were utilized to screen PDAC-characteristic glycosylation genes. An optimal model was constructed using 5 genes. Experimental Validation: In vitro experiments (CCK-8, Transwell migration/invasion, scratch assay) were conducted. Results: Glycosylation & Cell Types: High-glycosylation fibroblasts exhibited stronger activity in intercellular communication and signal pathway enrichment. MAN1C1 was highly expressed in active cancer-associated fibroblasts (aCAFs), and low expression was associated with a good prognosis for patients. Clinical Prognosis: MAN1C1 expression was significantly correlated with immune infiltration levels and immune-related markers. High MAN1C1 expression was associated with poorer overall survival, demonstrating its value as a potential prognostic marker. Logistic regression, COX regression, and LASSO analysis based on TCGA-PAAD clinical subgroups confirmed that patients with high MAN1C1 expression had a worse prognosis. ROC curve analysis indicated that MAN1C1 possesses good diagnostic capability. Conclusions: The glycosylation level of fibroblasts in the PDAC tumor microenvironment is significantly elevated. As a key glycosylation-related gene, MAN1C1 expression is closely related to patient prognosis. High expression of MAN1C1 inhibits the proliferation and migration of PDAC cells and affects intercellular interactions within the tumor microenvironment. MAN1C1 may serve as a potential therapeutic target for PDAC, providing a basis for developing therapeutic strategies targeting glycosylation pathways.

Workforce availability for cancer surgery in rural areas: A collaboration with the American Board of Surgery (ABS).

e13517 Background: Surgical care remains central to solid cancer treatment in adults. A shortage of surgeons, including in rural regions, poses a challenge to cancer treatment. The American Board of Surgery’s stated aims are to serve patients, society, and the specialty of surgery by setting standards in surgical education and practice. We evaluated the distribution of ABS-identified surgeons in USA by rurality of ZIP code to inform strategies to strengthen the surgical workforce and improve nationwide cancer care access. Methods: After ABS and institutional IRB approval, we linked data from ABS and US Census Bureau to identify rural-urban differences in surgeon supply, demographic profiles, and training backgrounds in the USA. US Census 2020 data was used to align variation in ABS-identified surgeon (regardless of current certification status) distribution across ZIP codes with USDA Economic Research Service rurality designations and aggregated as 50 state composites. ABS surgeon counts were converted to rates per 100,000 state population. Rurality was quantified as the percentage of state population living in US Census Bureau-defined rural areas. The association of state-level rurality and surgeon rates were compared using a gamma regression model. Results: ABS general surgery data accessed March 2025 listed 20,478 surgeons with designated addresses ("ABS-identified"), of whom 16,639 (81.3%) maintained active ABS certifications. In analyses of US Census and ABS data, there was no unadjusted association between percent rural population and the rate of ABS-identified surgeons per 100,000 state population (p = .693). A high degree of variation was observed in the urban and rural workforce overall; pronounced inter-state variation was noted, even between states with similar degrees of rurality. However, a strong correlation was noted between relative rurality of state and higher % of ABS-identified rural surgeons (Pearson r = 0.73). Conclusions: Surgery remains a crucial element of cancer care. Variation in surgeon and health care worker supply exist in the USA, along with variation in cancer screening, diagnosis, and outcomes. Our work demonstrates the complexity of combating previously described inferior cancer results in rural populations with simple numeric workforce calculations including surgeons per geographic unit. Further work should assess the contribution of factors including rural isolation, distance to provider and center, feasibility of patient travel for care, and potential outreach strategies. Understanding variability in the workforce available for cancer surgery will be necessary to improve access to guideline-directed cancer care across our entire population, including in rural regions, and will be essential to improving cancer outcomes in the USA. (The expertise of Carol L. Barry, PhD, of the American Board of Surgery, is gratefully acknowledged) .

Twenty years of colon cancer epidemiology and treatment patterns in São Paulo, Brazil: A population-based analysis of observed vs. expected treatment utilization.

e13625 Background: Colon cancer disproportionately impacts survival in individuals living in low to middle-income countries, with higher incidence-to-mortality ratios compared to high-income countries. In this large retrospective cohort study, we examine the stage distribution and survival outcomes for colon cancer over time in São Paulo, Brazil, and compare observed treatment prescription to model-based estimates. Methods: Using the São Paulo Oncocentre Foundation (FOSP) database, we identified patients diagnosed with colon cancer between 2000 and 2019. Demographic, socioeconomic, and cancer diagnosis and treatment variables were extracted. Survival data was analyzed using Kaplan-Meier curves. Actual chemotherapy, radiotherapy and surgery utilization were compared to estimates of optimal treatment utilization based on published models. Results: 32,065 cases of colon cancer were included in this cohort. 49% were male, and the median age was 63. Most patients presented with late-stage disease (30.3% with stage III and 28.4% IV). Stage distribution has remained stable over time. The median overall survival ranged from 13.7 years for those with stage I disease, to 1 year with stage IV disease. Actual chemotherapy utilisation was higher than expected for stage I and stage II disease, but lower than expected for stage III and IV disease. The use of surgery was lower than expected for Stage I-III disease, and higher than expected for stage IV disease. Conclusions: The stage distribution of colon cancer in São Paulo, Brazil has remained stable over time, while survival has improved. Despite this, gaps exist between expected and optimal treatment utilization, highlighting areas for further research and investment.

Financial and time toxicity among patients with cancer enrolled in pharmacotherapy clinical trials: Systematic reviews.

e24053 Background: Financial and time toxicity are increasingly described as burdens of cancer care, yet their magnitude among patients enrolled in pharmacotherapy clinical trials is poorly characterized. We conducted two systematic reviews to quantify the financial and time burdens experienced by cancer trial participants. Methods: We searched MEDLINE, Embase, and CENTRAL (through June 2025) for studies reporting financial or time toxicity among cancer patients enrolled in pharmacotherapy trials. Studies were included if they reported >=1 toxicity outcome. Financial toxicity outcomes included direct medical and indirect non-medical (ie housing, transportation, and lodging) out-of-pocket costs (adjusted to 2025 USD). Time toxicity was defined as days per month with any healthcare contact, including planned (protocol-specified) and unplanned encounters. Data were synthesized descriptively. Results: Three studies reported on financial toxicity, all from the US. Direct expenses ranged from $256–$301/month, while indirect expenses exceeded $828/month, with some patients incurring $3,367–$6,857/month. Total toxicity is multi-fold higher than non-trial participants. Four studies (from Canada, US, Australia and Italy) reported on time toxicity. Patients spent 7.6 days/month in healthcare contact, approximately twice that of non-trial participants. Planned days averaged 2.2/month and unplanned days 2.0/month; the highest burden occurred in the first month of trial enrollment. Higher time toxicity was associated with worse physical function, disease progression, and reduced overall survival. Conclusions: Cancer patients in pharmacotherapy trials experience financial and time burdens, far greater than non-participants. Incorporating standardized measurement and transparent reporting of toxicity into trial design and informed consent can better support equitable participation, improve patient-centered decisions, and guide interventions that meaningfully reduce avoidable burden.

Understanding circulating tumor DNA (ctDNA) test uptake among diverse cancer patients: A real-world evidence study.

e23374 Background: Circulating tumor DNA (ctDNA) testing is increasingly used in oncology for clinical indications including minimal residual disease (MRD) assessment and blood-based comprehensive genomic profiling (CGP). An understanding of real-world ctDNA utilization across cancer types, metastatic status, and clinical contexts is essential for optimal cancer care. Methods: Using the de-identified UCSF Clinical Data Warehouse (CDW), we conducted a retrospective cohort study of patients with documentation indicating ctDNA testing being discussed or performed between 2019 and 2025. Demographic characteristics, primary cancer type, and metastatic status were extracted from structured EHR data. Clinical documentation related to ctDNA was analyzed using an LLM-based extraction pipeline on UCSF Versa (ChatGPT on Microsoft Azure) to classify ctDNA-related statuses, including testing recommendation, test ordering, and reported results (positive, negative, inconclusive). Results: We identified 2,250 patients who underwent or discussed ctDNA testing, with 78.5% occurring in 2022 or later; indications were predominantly for MRD monitoring (86.2%), with 13.8% for CGP. Patients were predominantly aged 55–74 years (48.3%), male (55.7 %), non-Hispanic White (59.1%), and had metastatic disease at the initial ctDNA testing or discussion (38.3%). Gastrointestinal cancers were the most common tumor type for both MRD (27.7%) and CGP (20.3%). Among 1,940 patients with MRD-indicated ctDNA testing or discussion, ctDNA results were available for those tested, of whom 204 (10.5%) were positive and 409 (21.1%) were negative. Among the 94 ctDNA-positive patients who received anticancer pharmacotherapy at UCSF, 39 (41.4%) continued treatments after the last available ctDNA result. In comparison, among 179 ctDNA-negative patients who received anticancer pharmacotherapy, 104 (58.1%) discontinued treatments. Overall, our findings highlight the growing role of ctDNA in informing treatment decisions in routine oncology practice. Conclusions: In this real-world academic hospital cohort, ctDNA testing was predominantly used for MRD monitoring, with discussion and testing trends reflecting its increasing adoption in oncology practice.

An audit of initial experience of stereotactic body radiotherapy for extracranial oligometastases.

e23333 Background: To retrospectively review the toxicity and early outcome data from patients who have received stereotactic body radiotherapy (SBRT) for extracranial oligometastases in our institution. Methods: Eligible patients had ≤3 extracranial metastases and performance status ≤2. Prior systemic therapy and radical treatment of oligometastastic relapse with any standard treatment modality was permitted. Follow-up consisted of clinical examination, and radiological assessments. RECIST criteria was used for defining progression events. Toxicity was evaluated using CTCAE v5.0. Local control, progression-free survival (PFS) and freedom from widespread distant metastasis were calculated. Results: Between August 2023 and April 2025, 22 patients with 43 metastases received SBRT (range 1–3 per patient). Most common sites were lymph nodes(19), liver(14) ad spine(10). The median follow-up was 12.5 months (range 0–20.4). The median PFS was 12.5 months (1 year PFS 57%); 1 year local control 96%. At 1 year, 76% of patients were free from widespread distant metastases. No ≥ grade 3 acute or late toxicity was observed. Conclusions: SBRT for extracranial oligometastases demonstrated excellent early local control with minimal toxicity. These findings warrant confirmation with longer follow-up and randomized controlled trials to determine the impact on survival outcomes when added to standard care.

Inpatient CAR-T safety in the United States: Severe ICANS and CRS by donor source and antigen target (NIS 2022–2023).

e19006 Background: The field of CAR-T is rapidly expanding, with emerging allogeneic (donor-derived) platforms and multiple commercial products being used across hematologic malignancies. Comparative real-world national inpatient estimates of severe cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) across donor source and antigen target class remain limited, with existing comparisons often indirect or confined to specific products, trials, or registries. We evaluated severe inpatient toxicities and mortality after CAR-T by donor source and antigen target class in a nationally representative U.S. inpatient cohort. Methods: We performed a retrospective cross-sectional analysis of the HCUP National Inpatient Sample (NIS) data from 2022 to 2023. CAR-T hospitalizations were identified using ICD-10-PCS codes and stratified by donor type (autologous vs. allogeneic) and commercial product, further stratified by target antigen (CD19 vs. BCMA). Severe toxicities were captured using ICD-10-CM diagnosis coding for CRS and ICANS, with high-grade defined as grade 3–5. In-hospital mortality was obtained from the NIS discharge disposition mortality indicator. The primary outcome was high-grade ICANS (3–5); the secondary outcomes were high-grade CRS (3–5) and in-hospital mortality. Group differences used χ² tests (two-sided). Results: We identified an estimated 10,105 CAR-T hospitalizations: 9,485 autologous and 620 allogeneic. High-grade CRS was uncommon and similar between cohorts (autologous 3.8% [365/9,485] vs allogeneic 3.2% [20/620]; p=0.43). High-grade ICANS was markedly higher with autologous CAR-T (9.7% [920/9,485]) than allogeneic CAR-T (2.4% [15/620]; p<0.001). In-hospital mortality was low and not statistically different (2.2% [205/9,485] autologous vs. 3.2% [20/620] allogeneic; p=0.082). Among the most common commercial products, utilization was highest for axicabtagene (Yescarta, 31.1%), idecabtagene (Abecma, 12.8%), ciltacabtagene (Carvykti, 11.3%), brexucabtagene (Tecartus, 9.8%), and tisagenlecleucel (Kymriah, 5.4%). High-grade ICANS clustered in CD19 therapies [Tecartus 18.2% (180/990), Yescarta 15.4% (485/3,140), Kymriah 10.9% (60/550) and were lower with BCMA therapies (Abecma 4.7% (60/1,290), Carvykti 1.3% (15/1,140)]. Pooled by target, high-grade ICANS was 15.5% for CD19 vs 3.1% for BCMA (p<0.001). In-hospital mortality remained low across products (0.8%–3.0%) and was similar by target class (CD19 2.0% vs. BCMA 1.4%; p=0.078). Conclusions: In national inpatient data, ICANS differed significantly by donor source and antigen target, with lower high-grade ICANS in allogeneic and BCMA-targeted CAR-T. The inpatient mortality remained low across therapies. These findings support ongoing post-marketing surveillance and risk-adjusted analyses as CAR-T adoption evolves.

Population-level trends and geographic disparities in pancreatic cancer mortality among individuals with psychoactive substance use disorders: A retrospective analysis.

e22591 Background: Pancreatic cancer is a very lethal malignancy with persistently poor outcomes. Individuals with mental and behavioral disorders due to psychoactive substance use represent a vulnerable population that may experience disproportionate cancer mortality. This study examined temporal trends and disparities in pancreatic cancer mortality among adults with psychoactive substance use disorders in the United States from 1999 to 2023. Methods: The Center of Disease Control (CDC) mortality database was used to extract death certificates data encompassing the International Classification of Diseases 10th Revision (ICD-10) codes C25 for pancreatic cancer and F10-F19 for mental and behavioral disorders due to psychoactive substance use from the years 1999-2023. Joinpoint regression was employed to assess the average annual percent change (AAPC) with a 95% confidence interval (CI). A p value of less than 0.05 represented statistically significant trend. Results: From 1990 to 2023, the overall AAMR rates increased from 0.1 in 1999 to 1.32 in 2023 (AAPC: 11.07; 95% CI: 4.76 to 17.75; p< 0.000001). The highest AAMR was shown by Non-Hispanic Whites (NH White) rising from 0.09 in 1999 to 1.53 in 2023 (AAPC: 12.09; 95% CI: 6.98 to 17.45; p< 0.000002) followed by non-Hispanic Blacks (AAPC: 8.91; 95% CI: 4.25 to 13.78; p< 0.00013) and Hispanic or Latinos respectively (AAPC: 1.39; 95% CI: -0.92 to 3.75; p< 0.24) The overall AAMR in rural areas (1.07) was much higher than urban areas (0.81). North Dakota (2.21) and Vermont (1.77) were the states with highest AAMR respectively. The Midwest shared the highest burden of AAMR among all the regions (AAPC: 13.80, 95% CI: 3.73 to 24.85; p< 0.006228). Conclusions: The rising trend of pancreatic cancer in adults with psychoactive substance use in mental disorders in males, Non-Hispanic White individuals, rural areas, North Dakota, and the Mid-west region underscore the need for targeted health policies. While awareness of the importance of mental disorders is growing, further studies are needed on biological and behavioral links between psychological distress and rapid tumor progression.

Primary breast malignancies in adolescents and young adults: The MD Anderson Cancer Center experience.

10006 Background: Primary malignancies of the breast rarely affect adolescents and are uncommon in young adults. Limited information is available about their clinicopathologic characteristics and outcomes. The 5-year overall survival (OS) for women with breast cancer, not including ductal carcinoma in situ, exceeds 90%. However, it remains unclear whether adolescents and young adults experience similar outcomes compared with older patients. Methods: We conducted a retrospective study of all patients aged 0–25 years with primary breast malignancies seen at MD Anderson Cancer Center between 2000 and 2024. Demographics, histology, staging, treatment, and outcome data were collected. Event-free survival (EFS) and OS were estimated using the Kaplan–Meier method. Log-rank test was used to analyze patient outcomes by histology. Results: A total of 110 patients were identified. Median age at diagnosis was 23.9 years (range, 15.7–25.5). Two patients were male, 44.9% were White, 27.7% Hispanic, and 15.9% Black. The most common tumor histology was invasive ductal carcinoma (n=83, 75.5%), followed by sarcoma and malignant phyllodes tumors (n=14, 12.7%), carcinoma in situ (n=7, 6.4%), and rare histologic subtypes (n=6, 5.5%). Family history of breast cancer was present in 53.6% of patients and ovarian cancer in 9%. Of 81 patients with germline genetic testing, 25 (30.9%) had a cancer predisposition syndrome: Li-Fraumeni (n=9), BRCA1 (n=8), BRCA2 (n=4), ATM (n=2), other (n=2). Eleven patients (10%) had metastatic disease at presentation to bone, lung, distant lymph nodes, and liver. Among the 96 carcinoma cases, 36 (37.5%) were estrogen or progesterone receptor-positive and HER2-negative; 25 (26%) were HER2+, and 32 (33%) were triple-negative. Of the 110 patients, 69 (62.7%) received neoadjuvant chemotherapy, 37.6% of whom achieved a pathologic complete response, and 46.3% a partial response. Most patients (92.7%) had surgery (mastectomy 87.2% or lumpectomy 9.8%), 67.2% received radiotherapy, and 25.4% targeted therapy. Following treatment, 56 (51%) patients received adjuvant endocrine therapy. The 5-year EFS and OS for the cohort were 30% (95% CI, 22.6-39.9) and 71.8% (95% CI 62.9-82), respectively, and are presented by histology in the table. EFS (p=0.023) but not OS (p=0.36) was associated with histologic type. Conclusions: Primary breast malignancies in adolescents and young adults have distinct characteristics with a high frequency of family history and genetic predisposition syndromes and appear to be associated with lower survival compared with breast cancer in older patients. Histology No. of patients 5-year EFS (%) (95% CI) 5-year OS (%) (95% CI) Invasive ductal carcinoma 83 31.3 (22.8, 43.1) 68 (57.9, 80) Sarcoma and malignant phyllodes tumors 14 28.6 (12.5, 65.4) 82.1 (62.1, 100) Carcinoma in situ 7 42.9 (18.2, 100) 100 (100, 100) Rare histologic subtypes 6 NA 100 (100, 100)

Patient-reported outcome planning and reporting in CAR-T and CD3xCD20 bispecific antibody trials for relapsed/refractory lymphoma: A cross-sectional analysis (2017–2025).

e19107 Background: Patient-reported outcomes (PROs) are increasingly prioritized in lymphoma trials to contextualize benefit-risk and treatment feasibility. However, the extent to which lymphoma trials that plan PRO collection subsequently report PRO results remains unclear, particularly across novel treatment platforms. Methods: We conducted a cross-sectional analysis of interventional adult lymphoma trials registered on ClinicalTrials.gov from January 1, 2017 through December 31, 2025 evaluating CAR-T or CD3xCD20 bispecific antibodies. For each unique trial, we abstracted whether PROs were prospectively planned in the registry (PRO endpoint and/or instrument specified), instruments used, and whether PRO results were publicly reported in any associated conference abstract or manuscript. Among trials with planned PROs and any dissemination (abstract/manuscript), we evaluated PRO reporting completeness (instrument identified, completion rates, longitudinal reporting, missing data considerations, and clinically meaningful change thresholds). Results: Seventy-four trials met inclusion criteria (61 CAR-T, 13 bispecific). PROs were prospectively planned in 20/74 (27%) trials: 16/61 (26%) CAR-T and 4/13 (31%) bispecific. Common instruments included EORTC QLQ-C30, FACT-Lym/LymS, and EQ-5D (with occasional SF-36). Among trials with planned PROs and any public dissemination (n=11), PRO results were reported in 4/11 (36%). Reporting differed by platform: 2/9 (22%) CAR-T trials vs 2/2 (100%) bispecific trials reported planned PRO results. When PROs were reported, completeness was heterogeneous: dedicated PRO manuscripts demonstrated longitudinal trajectories, completion rates, and clinically interpretable change metrics, whereas several efficacy publications/abstracts omitted planned PRO findings. Conclusions: In modern lymphoma trials, PRO assessment is planned in only 1 in 4 studies, and most trials with planned PROs do not report PRO results when outcomes are disseminated. Standardized expectations for PRO reporting (including completion, longitudinal change, and clinically meaningful thresholds) are needed to improve transparency and interpretability across CAR-T and bispecific platforms.

Safety and feasibility of accelerated consolidative gamma knife radiotherapy following brain metastases resection.

e14020 Background: Consolidative radiotherapy is the standard of care following surgical resection of brain metastases; however, the optimal timing remains controversial. The authors report their institutional experience evaluating the safety, feasibility, and clinical outcomes of accelerated postoperative stereotactic radiosurgery (SRS). Methods: This is a retrospective analysis of a prospectively maintained SRS registry at a tertiary academic medical center. Patients with brain metastases who presented between 2013 and 2025 and underwent surgical resection followed by postoperative SRS were included. The Early group comprised patients who received consolidative SRS within 14 days of surgical resection. For comparison, the most recent 50 patients in the registry who were treated with consolidative SRS between 15 and 30 days postoperatively were selected as the standard group. A 10Gy single fraction constraint was applied to the skin for SRS planning. Results: The early group included 146 patients who underwent surgical resection of 155 brain metastases. Baseline demographic characteristics were comparable between the early and standard groups. Both cohorts had similar durations of clinical and radiographic follow-up; however, the early group had a significantly longer postoperative length of stay (5.2 vs 3.0 days, p = 0.001). Primary cancer types were similarly distributed between groups, except for breast cancer, which tended to be more prevalent in the standard group (7.5% vs 16.0%, p = 0.08). Cerebellar metastases were more common in the standard group (13.5% vs 28.8%, p = 0.012). Hypofractionated regimens (2, 3, or 5 fractions) were employed in both cohorts (7.7% vs 15.1%, p = 0.10). The Early group had a significantly smaller mean preoperative tumor volume (15.0 vs 21.8 cm³, p = 0.003) and a smaller mean postoperative cavity prescription isodose volume (26.2 vs 34.7 cm³, p = 0.042). In contrast, postoperative cavity volume, number of additional lesions treated during the same SRS session, total treatment volume, and total prescription isodose volume were similar between the two groups. The highest and lowest isodose lines traversing the surgical wound at the deepest and most superficial levels, respectively, were comparable between the groups, although the scalp volume receiving >10 Gy tended to be lower in the early group (0.8 vs 2.2 cm³, p = 0.09). There were no statistically significant differences in wound-healing complications (3.4% vs 2.0%, p = 0.60), local recurrence (12.4% vs 20.0%, p = 0.70), or rates of radiation necrosis (14.7% vs 17.1%, p = 0.70). Conclusions: Accelerated postoperative consolidative SRS can be well tolerated, with no observed increase in wound-healing complications or radiation necrosis. Completion of consolidative radiation treatment early post-operatively may facilitate earlier return to systemic therapy and should be considered when possible.

Influence of low-coverage whole-genome sequencing–based urinary tumor fraction and chromosomal instability on recurrence risk stratification in systemic immunotherapy-treated non–muscle–invasive bladder cancer.

4603 Background: Urinary tumor DNA (utDNA) is increasingly explored for prognostic assessment in bladder cancer, but most studies rely on a simple positive/negative classification, and its prognostic value in patients receiving systemic immune checkpoint inhibitors (ICIs) remains unclear. Low-coverage whole-genome sequencing (LC-WGS) of urine enables low-cost quantitative assessment of tumor fraction (TF) and chromosomal instability (CIN), providing richer molecular information than conventional binary utDNA status. We evaluated whether LC-WGS–derived TF and CIN improve prognostic stratification in ICI–treated high- and very high-risk non–muscle–invasive bladder cancer (NMIBC). Methods: Patients with high- or very high-risk NMIBC were enrolled in a prospective cohort treated with ICI tislelizumab plus low-dose nab-paclitaxel. Pretreatment urine samples were collected and analyzed using LC-WGS to derive TF and CIN. Clinicopathologic variables were collected at baseline. The primary endpoint was 2-year recurrence-free survival (RFS). Prediction models were constructed using clinicopathologic features (tumor size, number, concomitant carcinoma in situ, lymphovascular invasion) alone and in combination with TF and CIN. Results: A total of 35 patients were included. After a median follow-up of 27.3 months, 11 patients experienced disease recurrence. Models based on clinicopathologic features alone demonstrated limited discrimination for 2-year RFS (AUC = 0.61). Higher urinary TF and CIN were significantly associated with increased recurrence risk (TF: HR 2.18, 95% CI 1.29–3.97, p = 0.004; CIN: HR 2.74, 95% CI 1.41–5.32, p = 0.002). Incorporation of TF improved discrimination (AUC = 0.71), and further addition of CIN achieved the highest performance (AUC = 0.80; ΔAUC = 0.19 vs clinical model, p = 0.01). Patients classified as high molecular risk based on combined TF and CIN had significantly lower 2-year RFS than those at low molecular risk (HR 3.92, 95% CI 1.62–9.48, p = 0.002). Notably, the molecular-only model incorporating TF and CIN demonstrated discrimination comparable to the clinicopathologic-integrated model (AUC = 0.79 vs 0.80, p = 0.68), suggesting that urinary genomic features alone may provide sufficient information for recurrence risk stratification in this setting. Conclusions: Urinary TF and CIN derived from cost-effective LC-WGS substantially improved recurrence risk stratification beyond conventional tumor characteristics in NMIBC patients treated with systemic immunotherapy. These findings suggest that urine-based molecular profiling may offer a practical and scalable complement to conventional clinicopathologic risk assessment for baseline risk stratification and post-therapy management.