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daNIS-3: A phase II platform study of NIS793 and anti–PD-1 combined with standard of care (SoC) anti-cancer therapy for the second-line (2L) treatment (tx) of microsatellite-stable colorectal cancer (MSS CRC).

3529 Background: Despite advances in tx of MSS CRC including targeted tx, the prognosis remains poor. The daNIS-3 study (NCT04952753) evaluated efficacy and safety of anti-TGFß monoclonal antibody NIS793 (NIS) and anti-PD1 tislelizumab (TISLE) with SoC as 2L tx for MSS CRC patients (pts). Methods: This open-label, multicenter study included safety run-in (SRI) Arm 1a: NIS + SoC (bevacizumab [Bev] + FOLFIRI), Arm 1b: NIS + SoC (Bev + mFOLFOX6) followed by Arm 2a: NIS + TISLE + SoC (Bev + FOLFIRI), Arm 2b: NIS + TISLE+ SoC (Bev + mFOLFOX6) to determine NIS recommended phase 2 dose (RP2D) for expansion phase (EP). FOLFIRI and mFOLFOX6 were evaluated independently. While EP included same investigational arms as SRI (Arm 2b not opened for enrollment), additional SoC arm was added. Primary endpoint was progression-free survival (PFS) in EP; secondary endpoints were PFS for SRI, overall response rate (ORR), disease control rate (DCR), duration of response (DOR) and time to response (TTR) using RECIST V1.1, pharmacokinetics (PK), immunogenicity, safety, and tolerability. Based on data monitoring committee recommendation, study was terminated on 31-07-2023 due to unfavorable benefit-risk profile. Results: As of 20-01-2025, median (95% CI) PFS in EP was 5.1 months (mo) (3.6–5.7), 3.7 mo (2.2–5.6), and 7.4 mo (5.5–9.4) for Arms 1a&b, Arm 2a, and SoC, respectively (HR vs SoC [95% CI]: Arms 1a&b, 2.06 [1.34–3.18]; Arm 2a, 1.65 [0.90–3.02]). Secondary endpoints are summarized in Table. PK of NIS and other drugs were similar in EP and SRI. All pts were ADA negative at baseline and during the study. NIS RP2D for Arms 1a&b, and 2a was 2100 mg Q2W. In SRI and EP, overall adverse events (AEs) were comparable across all arms. In EP, grade ≥3 AEs were higher in Arm 1a (67.7%) and 1b (66.7%) compared to Arm 2a (55.2%) and SoC (58.7% & 42.9%). Higher incidence of serious AEs was reported in Arm 1a (49.2%) compared to Arm 2a (31%) and SoC (30.4% & 42.9%). Higher deaths were observed in Arm 1a (50.8%) and 1b (60.0%), mostly attributed to underlying malignancy (MSS CRC). Most common AEs of special interest of NIS were infusion-related reactions, hemorrhage, and skin toxicity, consistent with known safety profile of NIS. Conclusions: Overall AEs were comparable, but a higher incidence of grade ≥3 AEs vs SoC were observed. NIS arms showed a deleterious PFS outcome in MSS CRC pts. Clinical trial information: NCT04952753 . Secondary endpoints * SRIArms 1a (N = 13) & 1b (N = 9) SRIArms 2a (N = 10) & 2b (N = 8) EPArms 1a (N = 67) & 1b (N = 13) EPArm 2a (N = 29) SoC(N = 53) mPFS, mo (95% CI) 3.6 (1.9, 7.3) 2.1 (1.8, 4.3) – – – ORR, n (%) 1 (4.5) 0 7 (8.8) 4 (13.8) 8 (15.1) DCR, n (%) 14 (63.6) 8 (44.4) 53 (66.3) 19 (65.5) 42 (79.2) mDOR, mo (95% CI) 9.4 (NE, NE) NE 9.5 (4.0, NE) NE 11.1 (3.8, NE) mOS, mo (95% CI) 10.2 (5.8, 20.8) 11.0 (6.2, 15.7) 12.8 (8.0, 14.2) 10.9 (6.1, NE) NE (11.6, NE) *SoC+FOLFIRI/mFOLFOX6 presented together due to similar efficacy.

Radiotherapy followed by systemic therapy and tislelizumab in microsatellite-stable rectal cancer with synchronous unresectable metastases: Updated results of the MIRACLE-2 study.

3578 Background: Microsatellite-stable (MSS) tumors comprise ~95% of metastatic colorectal cancer cases and exhibit intrinsic resistance to immunotherapy. Emerging evidence suggests systemic therapy may enhance immunotherapy responsiveness, while radiotherapy could improve efficacy by overcoming resistance and reducing tumor burden. The MIRACLE-2 study evaluated the safety and efficacy of combining radiotherapy with systemic therapy and tislelizumab as first-line treatment for unresectable metastatic MSS rectal cancer (RC). Methods: MIRACLE-2 was a prospective, single-arm, phase II study. Inclusion criteria: MSS RC with primary tumor ≤10 cm from anal verge on MRI and synchronous unresectable metastases. Patients received hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or SBRT for metastases, followed by systemic therapy: FOLFOX-bevacizumab-tislelizumab for RAS/BRAF-mutant patients or FOLFIRI-cetuximab-tislelizumab for wild-type patients. Reassessment every 8 weeks. Patients achieving resectable disease underwent primary tumor resection and metastasectomy/local ablative therapies for metastases. For patients unable to preserve anal sphincter, a watch-and-wait (WW) strategy was considered if clinical complete response (cCR) of primary tumor was achieved. Otherwise, systemic therapy continued until progression/intolerable toxicity. Primary endpoint: ETS rate (≥20% target lesion reduction at 8 weeks post systemic therapy initiation). Secondary endpoints: disease control rate (DCR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety. Results: As of December 31, 2025, efficacy data were available for 50 patients (38 males, 76.0%; median age 57 years, range 30-73). Among these, 52.0% had liver metastases, 8.0% lung metastases, and 40.0% both liver and lung metastases. RAS/BRAF mutations were detected in 56.0% of primary tumors. Median treatment courses: eight (range 3-12). Overall, 18% (9/50) attained no evidence of disease (NED). ETS rate: 76.0%; DCR: 88.0%. Median follow-up: 19.9 months (95% CI: 16.4-23.4). Among 34 patients with complete/partial response, median DOR: 8.0 months (95% CI: 5.2–10.8), with 1-year DOR rate of 20%. Median PFS: 9.3 months (95% CI: 7.1-11.5), with 1-year PFS rate of 33.4%. Median OS: 23.2 months (95% CI: 15.1-31.3), and 1-year OS rate: 93.3%. No grade 5 treatment-related adverse events (TRAEs) occurred. All-grade TRAEs: lymphopenia (95.9%), anemia (91.8%), and leukopenia (69.4%). Grade 3/4 TRAEs: lymphopenia (36.7%), neutropenia (26.5%), and leukopenia (20.4%). Conclusions: The combination of radiotherapy, systemic therapy, and tislelizumab showed a high ETS rate and manageable safety profile in first-line unresectable MSS RC. Long-term outcomes require further follow-up. Clinical trial information: NCT05359406 .

Patient-level OS prediction in NSCLC combining real-world data and published trial results.

e20526 Background: The majority of early-phase clinical trials in oncology are single-arm trials. External comparator arms can provide important contextual information to interpret results and to inform the design of future trials. But patient-level trial data may be lacking, especially because oncology is characterized by rapidly evolving standards-of-care for increasingly granular subgroups. Real-world data (RWD) and summary trial results offer complementary but incomplete pictures of the effects of therapies on patients. The difficulty of combining these sources of information hampers optimal decision-making in trial planning, design, and analysis. Methods: We developed a machine learning (ML) model that integrates patient-level RWD with summary statistics from recent trial publications. The model generates patient-level predictions of outcomes under existing treatments that conform to the results of past RCTs in the aggregate. This provides a novel approach to integrating RWD into granular analyses while maintaining the gold-standard status of randomized trial evidence. The core of the model consists in a foundational pan-cancer transformer model that was trained on RWD from a collection of detailed clinical and genetic data from roughly 250k tumor biopsies [custom-processed versions of AACR GENIE, GENIE BPC NSCLC & CRC, and MSK-CHORD]. We demonstrate a novel calibration technique that allows us to conform the model’s survival predictions to match published results, incorporating one or many RCT results into its weights. Results: We demonstrate the capability of this approach to both interpolate between results of RCTs and to extrapolate to new trials. We calibrate the model to the full set of KEYNOTE trials in mNSCLC and show that it generates patient-level trial simulations across baseline cohorts and treatments within the KEYNOTE trial span while recapitulating observed outcomes at calibration points. We further demonstrate that the model recapitulates published control-arm results from the POSEIDON and LEAP-006 trials. Across PD-L1 expression strata, histologic subtype, KEAP1/STK11/KRAS mutation status, and the overall population, 90.9% (40/44) of median and 2–5-year OS estimates fell within reported 95% confidence intervals, with median absolute deviation 2.7% in the survival benchmarks. Conclusions: ML models integrating RWD with trial results enable accurate prediction of survival in a way that can simultaneously support granular analyses while conforming to gold-standard RCT results. Our approach enables the creation of external comparators to better evaluate the efficacy of new therapies. More broadly it supports data-driven decision-making in trial planning, trial analysis, and hypothesis generation.

Explainable machine learning for continuous transcriptomic modeling of metastatic risk in prostate cancer (MET-score).

5129 Background: Metastatic progression is the leading cause of mortality in prostate cancer, yet clinicopathological stratification incompletely identifies primary tumors with latent metastatic potential. Emerging evidence supports metastatic competence as a gradual transcriptional reprogramming, motivating molecular tools that capture continuous risk states. Methods: Transcriptomes from primary and metastatic prostate tumors (n = 766; PRIMARY = 507, MET = 259) spanning 16,234 gene features were integrated to train an interpretable XGBoost model. SHapley Additive exPlanations were used to derive a minimal 30-gene signature and define a continuous metastasis-likeness transcriptomic score (MET-score). MET-score was applied to primary tumors to quantify metastasis-likeness and characterize associated biology. External validation was performed in an independent primary prostate cohort profiled with exon microarrays (GSE21034) without model retraining. Results: The minimal 30-gene signature captured metastasis-associated signal with high discriminative performance (ROC AUC ≈ 0.98). In primary tumors (n = 507), MET-score exhibited a right-skewed continuous distribution (mean 0.0079, SD 0.0640; range 0.0023–0.9953), consistent with heterogeneous degrees of metastasis-like transcriptional activity within primary disease. Using a prespecified high-risk threshold at the 0.85 quantile (cutoff 0.002603), 81/507 (16.0%) primary tumors were classified as HIGH MET-score and 426/507 as LOW, identifying a subset with transcriptomic profiles most closely resembling metastatic disease. MET-score generalized robustly to GSE21034 while preserving its continuous structure and enabling molecular stratification despite platform differences and partial gene loss: 26/30 signature genes were present in the microarray cohort (missing C15orf40, ADIRF, CTC1, NTPCR). However, prognostic validation against clinical endpoints could not be performed because the publicly available metadata did not include clearly annotated time-to-event and event-status variables. Conclusions: An explainable 30-gene MET-score was developed to quantify metastasis-likeness as a continuous transcriptomic trait in primary prostate cancer. The score identifies a high-risk primary subset and transfers to an independent external cohort (GSE21034) without model retraining, supporting cross-platform robustness and prioritizing MET-score for clinical outcome validation in RNA-seq–annotated cohorts.

An innovative team approach to improve SCLC care across an integrated health system.

8111 Background: Small cell lung cancer (SCLC) is a highly aggressive cancer, with improved overall survival due to recent advancements in therapy. However, as many as 40% of patients (pts) may not receive guideline-concordant care for SCLC due to barriers including delays in diagnosis and referrals to oncology. We developed and implemented an electronic medical record (EMR) alert system based on ICD codes for early identification of pts with suspected SCLC and early intervention by thoracic medical oncology at University Hospitals Seidman Cancer Center. We hypothesized our intervention would increase rates of guideline concordant care and ultimately improve pt outcomes, compared to historical control. Methods: An informatics approach was used to identify pts with possible SCLC from 5/5/2024-5/17/2025 by incorporating Structure Query Language, Server Reporting Services, and text search of the EMR and pathology systems. Daily reports were reviewed by the thoracic medical oncology team, who intervened when needed to ensure appropriate staging and referrals. Clinicodemographic data was collected of pts with confirmed SCLC compared to a historical control of patients diagnosed between 2/5/2019-11/29/2021. Chi-square tests assessed statistical differences between the groups, and Kaplan-Meier (KM) survival analysis estimated overall survival (OS) and progression free survival (PFS). Results: 101 pts with SCLC were identified in the current group (C), and 130 pts in the historical group (H). Age, sex, smoking history, and baseline ECOG status, were similar between groups. A numerically higher percentage of pts in C were diagnosed with limited-stage SCLC (38.6%) compared to H (27.7%), p = 0.106). A numerically higher number of pts in C received guideline-concordant baseline imaging (93.1%) compared to H (83.8%, p = 0.05). Among pts who received treatment (tx), median time to tx was longer in C (19 days, interquartile range [IQR] 9-31) than H (13 days, IQR 5-22, p = 0.001). Pts in C were significantly more likely to receive 1st-line guideline-concordant tx than H (94.0% vs 83.3%, p = 0.02), although similar likelihood of enrolling in hospice before any therapy (12.9% vs. 11.5%, p = 0.917). Pts in C with progression were numerically more likely to receive 2 nd -line and 3 rd -line tx than H (61.3% vs. 57.1%; 78% vs. 53.1%, respectively). Pts in C had statistically significantly improved PFS compared to H (p = 0.008). Conclusions: Successful creation of an EMR alert system to identify SCLC significantly increased rates of guideline-concordant tx of SCLC. Although not statistically significant, pts were also more likely to receive guideline-concordant imaging and treatment in the 2 nd and 3 rd line settings compared to historical control.

Pathologic treatment effect and first recurrence behavior after curative liver surgery for HCC.

e16287 Background: Locoregional therapy (LRT) is frequently used before curative-intent liver resection or transplantation for hepatocellular carcinoma (HCC), yet it remains uncertain whether the degree of pathologic treatment effect provides independent prognostic information beyond tumor burden and biology. Methods: In a cohort undergoing curative-intent liver surgery (N = 284), we evaluated whether pathologic treatment effect (categorized as none/partial/complete) predicted (1) time to first recurrence (Cox proportional hazards), (2) early recurrence (≤24 months; multivariable logistic regression), and (3) extrahepatic involvement at first relapse among patients with recurrence (logistic regression; n = 80). Models adjusted for age, MELD, log10(AFP+1), tumor diameter, multifocality, and microvascular invasion, with surgery type (transplant vs resection) included as a key clinical covariate. Results: Pathologic treatment effect was not independently associated with time to recurrence or early recurrence (all p > 0.34). Larger tumor diameter and multifocality were consistently associated with higher recurrence risk, while transplantation (vs resection) was associated with lower recurrence risk and lower odds of early recurrence. Among patients who recurred (n = 80), transplantation was associated with increased odds of extrahepatic involvement at first relapse (OR 7.84, p = 0.020). Conclusions: Pathologic treatment effect did not improve prediction of post-operative recurrence outcomes beyond established tumor and treatment factors. Recurrence risk was primarily driven by tumor burden (diameter, multifocality) and surgery type. Among patients who recur, transplant recipients demonstrated higher odds of extrahepatic involvement at first relapse, supporting focused relapse-phenotype surveillance strategies in this subgroup. Key adjusted associations (multivariable models). Variable Time to First Recurrence HR (95% CI), p Early Recurrence ≤24 Months OR (95% CI), p Extrahepatic Involvement at First Relapse OR (95% CI), p* Partial vs none 0.77 (0.44–1.33), 0.341 1.08 (0.39–3.03), 0.880 1.57 (0.24–10.16), 0.634 Complete vs none 1.02 (0.69–1.51), 0.928 1.34 (0.68–2.63), 0.399 2.42 (0.83–7.04), 0.106 Transplant vs resection 0.43 (0.28–0.68), <0.001 0.15 (0.06–0.40), <0.001 7.84 (1.39–44.17), 0.020 Tumor diameter (per cm) 1.08 (1.02–1.14), 0.008 1.12 (1.02–1.22), 0.014 1.04 (0.91–1.18), 0.577 Multifocality (multiple tumors) 1.58 (1.06–2.37), 0.025 2.06 (1.04–4.10), 0.039 0.70 (0.23–2.10), 0.524

County-level residential radon exposure, testing patterns, and cancer incidence in Michigan.

e22542 Background: Radon is a well-established lung carcinogen and the second leading cause of lung cancer in the United States. Population-level studies evaluating radon exposure and cancer incidence have yielded inconsistent results, potentially due to heterogeneity in exposure assessment and testing practices. We evaluated county-level associations between residential radon exposure, testing patterns, and cancer incidence in Michigan. Methods: Residential radon test results (~99,300 tests) from the Michigan Department of Environment, Great Lakes, and Energy were aggregated to the county level. Radon exposure was assessed using mean concentration, percentage of tests exceeding the EPA action level, and EPA radon category (Levels 1–2 vs Level 3 reference). Age-adjusted cancer incidence rates (2017–2021) were obtained from NCI State Cancer Profiles. Negative binomial regression models evaluated associations between radon measures and incidence of 11 cancer types at the county level in Michigan, with and without adjustment for county-level smoking prevalence, median household income, percent male, percent age ≥65 years, and percent Black population. Correlation and rural–urban analyses were performed. Results: After covariate adjustment, no significant association was observed between any radon metric and lung cancer incidence (all adjusted p > 0.05). Null associations were also observed for other evaluated cancer types. Average radon levels did not differ between rural and urban counties. A modest positive correlation was observed between the percentage of tests exceeding the EPA action level and median household income (r = 0.22, p = 0.04). Conclusions: County-level residential radon exposure was not independently associated with cancer incidence after adjustment for key sociodemographic and behavioral factors. The association between elevated radon test prevalence and higher income suggests socioeconomic disparities in radon testing that may obscure true exposure patterns in lower-income communities, underscoring the need for equitable radon screening and mitigation strategies in cancer prevention.

Childcare provision during breast cancer radiation therapy: Piloting of the Waiting Room Watchers program through the Navigator-Assisted Hypofractionation (NAVAH) program.

e23113 Background: Childcare responsibilities remain a major barrier to treatment adherence among women undergoing cancer therapy. The Waiting Room Watchers (WRW) program, developed by My Sister’s Keeper Cleveland and funded through the Navigator-Assisted Hypofractionation (NAVAH) initiative at University Hospitals Cleveland Medical Center, was designed to provide trained sitters in hospital waiting areas during oncology visits and radiation therapy. The initiative was offered to all major cancer centers in Cleveland, Ohio. While all expressed strong interest in addressing this barrier, MetroHealth Cancer Center was the only site to formally adopt and implement the pilot during the initial phase. Methods: From March to August 2025, WRW operated at the MetroHealth Cancer Center in Cleveland, Ohio. Requests were submitted through a digital platform that enabled real-time scheduling, tracking, and documentation. Sitters completed CPR and First Aid training. Utilization, satisfaction, and operational impact were assessed using caregiver and hospital staff feedback surveys. Results: Six service requests were received during the pilot period. One request could not be accommodated due to same-day (<5-hour) notice, and two resulted in patient no-shows. Two patients were successfully served: one breast cancer patient with a 1 year-old child, and one Sickle Cell patient (due to the frequency of management within Medical Oncology) with an 8-year-old child, the latter using the service three times (no-showed once). All completed sessions (n=4) received 5/5 ratings for professionalism, compassion, and reliability. Hospital staff described WRW as “invaluable,” noting that the breast cancer patient would not have completed radiation therapy without this support. Conclusions: Waiting Room Watchers, implemented through the NAVAH program, removes a critical childcare barrier that would otherwise limit patients’ ability to complete cancer treatment. Its successful launch (the first documented instance of aiding in radiation therapy completion in breast cancer) demonstrates feasibility and potential for national scale to advance equity in cancer care delivery. Implementation of the WRW program during the pilot phase resulted in institutional readiness and patient-centered leadership. The program proved feasible, safe, and impactful—improving treatment adherence, caregiver support, and clinic efficiency, and resulted in the first instance of facilitating radiation therapy in breast cancer. Expansion of WRW to Oklahoma City is underway to broaden equitable access to care through the NAVAH framework in concordance with the ongoing NAVAH Phase I clinical trial.

Developing workshops to enhance self-efficacy among patients in cancer survivorship: A collaborative partnership between physiatry and a community cancer support network.

e13786 Background: Cancer survivors face physical, emotional and psychosocial challenges after treatment. There is evidence that rehabilitation can help restore function and quality-of-life in cancer survivorship, however it is underutilized. This is attributed to a lack of awareness among clinicians and patients, and a lack of clinical guidelines that incorporate rehabilitation. In 2021, Shah et. al demonstrated that their hope-enhancing workshop for breast cancer patients was feasible and efficacious, however, the benefits of workshops incorporating cancer rehabilitation have not been explored. This study evaluated the feasibility and preliminary effects of community-based educational workshops focused on cancer rehabilitation. Methods: Cancer Rehabilitation Education and Wellness is a formal partnership between a national rehabilitation health system and a national cancer support organization to promote awareness on survivorship topics. This study included data collected from two workshops– one focused on exercise in cancer survivorship, and one on cancer-related fatigue. Each session was one hour, with in-person & virtual participation. The workshops were free and public. They were led by resident physicians, skilled therapists, and social workers. The workshops incorporated slide-based content, an interactive session, and education on local resources. Participants were asked to complete optional pre- and post-workshop surveys. The primary outcome was feasibility determined by attendance, and secondary outcome was self-efficacy with an abbreviated Cancer Behavior Inventory . Results: Feasibility was demonstrated by recruitment of 35 patients over 6 months, with 57% of patients completing pre- and post-intervention surveys. Based on these data, patients report statistically improved expression of negative feelings about cancer, more content knowledge, and greater ability to perform daily activities following workshop participation. Conclusions: Community-based rehabilitation workshops are feasible, well-accepted by survivors, and integrate smoothly into provider workflows. This workshop model could be replicated by other health systems—with a team-based approach, committed community partnerships, and hybrid workshop delivery—in order to reach the most survivors and caregivers. This approach can bridge the gap between survivorship rehabilitation needs and accessible community resources.

Phase 1/2a study of concomitant radiotherapy with olaparib and temozolomide in unresectable high-grade glioma patients: Final results from the phase 2a step (OLA-TMZ-RTE-01).

2005 Background: Although the Stupp protocol (radiotherapy + temozolomide (TMZ)) remains the cornerstone of glioblastoma (GBM) first line treatment after surgery (resection or biopsy), the prognosis is still poor. PARP inhibitors, such as olaparib, may enhance the efficacy of radiotherapy and TMZ by amplifying their cytotoxic effects. We implemented a phase 1/2 trial to assess safety and efficacy of olaparib combined with TMZ concomitant with intensity modulated radiotherapy (IMRT) as a first line treatment in GBM patients (pts) following biopsy or subtotal resection. The phase 1 conducted in 30 pts concluded the recommended phase 2 dose (RP2D) of olaparib was 100 mg Q12H Day (D) 1-3, in concomitant with the Stupp protocol. We herein report results of the phase 2a. Methods: Pts were treated with adjuvant IMRT (60 Gy/30 fractions/6 wks), with concurrent daily oral TMZ (75 mg/m²). For the maintenance period (MT) from 4 wks after IMRT, pts received TMZ (150 mg/m², D 1-5 every 28 days, for 6 cycles). Oral olaparib was started at the RP2D the same day as IMRT, concurrently with the Stupp protocol and continued up to disease progression or unacceptable toxicity. The trial was conducted according to a two-step Case and Morgan design and required 55 assessable pts (37 in interim analysis), to assess the 12-month (mo) overall survival (OS) rate expected to be higher than 57%. Final Z-statistic>1.235 will confirm efficacy. All pts who received olaparib at RP2D were included in the analysis, including pts of the phase 1 step. Results: From 2020 to 2024, 68 pts were enrolled and treated in the phase 2a: 41 (60%) men, median age 59 yrs [range 20-70]. 67 pts (98%) had GBM and 1 (2%) IDH mutated anaplastic astrocytoma. Biopsy-only was performed for 27 pts (40%). ECOG performance status 0 for 34 pts (51%), 1 for 28 pts (42%) and 2 for 5 (7%). 11 pts (16%) stopped the study before MT, including 4 for grade 3-4 hematological toxicity. Among the 57 pts who began the MT, 5 stopped the treatment for hematological toxicity. 3 pts remain on treatment. Interim analysis conducted in March 2024 in 41 patients, with median follow-up o 7.6 mo, led pursuing the study, with a 12-mo OS rate of 72.9% [95%CI: 56.7-93.9]. At final analysis, after median follow-up of 17.2 mo, 48 deaths (71%) were observed. Median OS was 18.4 mo and 12-mo OS rate of 69.1% [95%CI: 59-81] (H0 rejection according to Z-statistic=1.29). Among hematological toxicities of interest, thrombocytopenia grade ≥ 3 was observed in 5 pts, neutropenia grade 4 in 4 pts, febrile neutropenia grade ≥ 3 in 1 pt and anemia grade ≥ 3 in 4 pts. One toxic death was observed (febrile aplasia). Conclusions: Intermittent olaparib (100 mg Q12H D1-3) combined with the Stupp protocol appears to be beneficial to improve survival of poor prognosis nonresected/partially resected GBM pts, with a safety profile quite similar to that of the standard chemoradiotherapy. Clinical trial information: NCT03212742 .

Process‐Driven Protonation in Benzothiadiazole‐Integrated Covalent Organic Frameworks: Activation of Peroxymonosulfate for Pollutant Oligomerization via Dominant Electron Transfer Process

ABSTRACT Traditional peroxymonosulfate (PMS) activation typically follows a static, catalyst‐centered paradigm, constrained by radical‐mediated pathways with limited selectivity and incomplete mineralization. Going beyond this convention, we established a process‐driven protonation strategy that steers PMS activation toward a dominant electron transfer process (ETP), enabling selective pollutant oligomerization. By developing benzothiadiazole‐integrated covalent organic frameworks (BT‐COFs) as a model platform, it was demonstrated that PMS addition intrinsically acidifies the reaction medium, triggering in situ framework protonation at specific nitrogen sites. This self‐induced protonation acts as a molecular switch, reorganizing the interfacial electronic structure and generating a polarized catalytic interface that facilitates directional electron transfer rather than radical generation. Consequently, the complete bisphenol A (BPA) removal within 5 min ( k obs  = 1.68 min −1 ) was achieved through an ETP‐directed oligomerization pathway, wherein the dynamic catalytic interface remains accessible through simple regeneration, maintaining excellent stability and robustness in complex water matrices. This work redefines the role of PMS as an active interfacial regulator and provides a dynamic, process‐adaptive conceptual framework for designing intelligent metal‐free systems for sustainable environmental remediation.

DNA-functionalized superparamagnetic Fe₃O₄ nanoparticles: In Vitro antioxidant and anticancer assessment in MCF-7 cancer cells

A peptide-guided strategy for kinase activation

Three‐Terminal Reconfigurable Volatile/Nonvolatile Light‐Emitting Memristor for Integrated Neuromorphic Display Systems

ABSTRACT Reconfigurable volatile/nonvolatile neuromorphic devices integrate brain‐like rapid learning with stable memory, providing a critical pathway toward edge‐intelligent systems. The integration of reconfigurable devices and light‐emitting functionality transforms the display from a passive output terminal into an integral hub of the intelligent system. However, integrating reconfigurable volatile/nonvolatile memory and light‐emitting functionality within a single device remains a major challenge because of the inherent conflicts among multiple functions and the constraints of conventional two‐terminal control. Here, for the first time, we present a three‐terminal reconfigurable volatile/nonvolatile light‐emitting memristor. The three‐terminal configuration provides control of the emission region and memory states, enabling seamless transition between volatile, nonvolatile, and light‐emission operations. By enabling spatial reconfigurability and temporal multiplexing of emission, the device improves scalability and simplifies system architecture and control, achieving a 69.23% reduction in data‐transfer volume and a 40% reduction in system component count compared with separated architectures. In addition, it offers direct visual feedback while facilitating continuous learning in neuromorphic computing systems. Finally, we implement an anomaly‐detection visualization system based on the reconfigurable volatile/nonvolatile light‐emitting memristor, demonstrating its ability to produce direct visual output while processing information, thus enabling an integrated memory‐compute‐display architecture for next‐generation edge‐intelligent display systems.

Predictors of knowledge and attitudes toward palliative care among patients with cancer: a cross-sectional study

Deletion of mitochondrial calcium uniporter enhances calcium signals by slowing calcium clearance and triggers adaptive transcriptomic remodeling

Site and extent of distant metastasis at diagnosis as used to stratify survival in head and neck cancer: A population-based analysis.

e18041 Background: Distant metastases in head and neck cancer (HNC) are associated with poor prognosis. Population-level data defining the prognostic impact of specific metastatic sites and multisite dissemination are limited. We compared overall survival by metastatic site and extent. Methods: Using SEER 17 Registries (2010–2017), we conducted a retrospective analysis of patients with HNC, classifying distant metastatic involvement by site (bone, lung, liver, brain). The study followed a prespecified protocol and was exempt from institutional review board oversight. Patients were categorized as having isolated single-site or multisite metastatic disease. Overall survival was estimated using Kaplan–Meier methods with log-rank testing. Multivariable Cox proportional hazards models adjusted for age, sex, and year of diagnosis were used to assess diagnosis-time prognostic associations. Analyses were conducted using complete-case methods. Results: Among 7,491 patients with head and neck cancer, 1,082 (14.4%) had distant metastases to bone, lung, liver, or brain. Lung metastases were most common (n=789), followed by bone (n=323), liver (n=180), and brain (n=31). Patients without distant metastases had a median overall survival (OS) of 28 months. Metastases involved a single organ in 81.0% (876/1,082) and were multisite in 19.0% (206/1,082), most frequently with liver metastases (63.9%) and least frequently with lung metastases (20.5%). Among patients with isolated metastatic disease, median OS differed by site: brain-only 3 months, bone-only 8 months, lung-only 9 months, and liver-only 11 months (log-rank p<1×10⁻¹⁶). For bone, lung, and liver metastases, multisite disease was associated with worse survival (bone: 8 vs 5 months, p=0.0055; lung: 9 vs 4 months, p=1.77×10⁻⁷; liver: 11 vs 5 months, p=0.0036), while brain metastases had poor outcomes regardless of extent (p=0.59). In multivariable Cox regression, metastatic site remained independently associated with OS. Compared with non-metastatic disease, brain metastases conferred the highest mortality risk (HR 3.92, 95% CI 2.74–5.59), followed by lung (HR 2.17, 95% CI 2.00–2.35), bone (HR 1.82, 95% CI 1.61–2.07), and liver metastases (HR 1.56, 95% CI 1.32–1.84) (all p<0.001). Conclusions: In this large, population-based SEER cohort, survival in metastatic head and neck cancer at diagnosis varied systematically by both metastatic site and extent of dissemination, with effects persisting after multivariable adjustment. Brain metastases defined a rare but uniformly high-risk presentation, while bone, lung, and liver metastases exhibited substantial prognostic heterogeneity that was further modified by the presence of multisite disease. These findings establish diagnosis-time metastatic site and extent as complementary determinants of survival.

Geographic disparities in availability of advanced therapies for myeloma from rural-urban access limitations: A population-based registry analysis.

e13511 Background: Autologous stem cell transplantation (ASCT) remains standard consolidation therapy for transplant-eligible multiple myeloma (MM) patients. Even though CAR-T therapies have emerged as promising options for relapsed/refractory disease, access remains limited. In Missouri, where 99 of 116 counties are classified as rural, access to both Auto-HSCT and CAR-T therapy remains largely confined to urban populations, potentially resulting in geographic disparities. To evaluate this hypothesis, we studied rural-urban differences in MM incidence, mortality, and access to advanced therapies in Missouri using multi-center registry data supplemented with CAR-T product acquisition information. Methods: A retrospective population-based multi-center analysis was conducted using data from the Missouri Cancer Registry and the BMT InfoNet for MM patients treated between January 2020 and December 2025. Counties were classified as urban (n = 17, including St. Louis City) or rural (n = 99) based on US Census definitions. We analyzed MM incidence and mortality rates (age-adjusted per 100,000 population) by sex, race (White, Black, Other), and geography (rural and urban). Auto-HSCT procedures were analyzed by sex, race, and geography during the study period. CAR-T acquisition data was obtained from centre-reported volumes for Ciltacabtagene autoleucel. Results: Approximately 2,900 MM cases were identified statewide between January 2020 and December 2025. The mean age at diagnosis was 67 years. Incidence was higher in urban (8.9 per 100,000) than in rural counties (5.6 per 100,000). Males had a higher incidence than females (~9.8 vs ~5.6 per 100,000). Black patients had a higher incidence (12-20 per 100,000) compared to White patients (5-8 per 100,000). Rural counties had a higher mortality rate of 4-6 per 100,000 compared to urban counties, which had a rate of 2-4 per 100,000. Mortality was also higher among males, 3-6 per 100,000, and Black patients, 5-7 per 100,000, compared to females, 1.5-3 per 100,000, and White patients, 2-4 per 100,000. There were 1142 autologous transplant procedures statewide during the study period. Auto-HSCT utilization by county of residence was higher in urban than in rural populations (114.6 vs 25.4 procedures per year). Ciltacabtagene autoleucel infusion uptake remained limited to 165 statewide during the 5-year study period, representing 5% of MM patients . Conclusions: Significant geographic disparities in MM care exist in rural-predominant states such as Missouri. Availability of both Auto-HSCT and CAR-T therapies remained limited statewide. These access disparities likely contribute to the observed higher mortality rates in rural counties. These findings underscore the need for health care policy changes addressing geographic barriers to ensure equitable access to advanced MM therapies.

Association of patient-reported stress and depression symptoms with ER-specific tumor transcriptional signatures in breast cancer (BC).

565 Background: Psychological distress is common among women with BC, yet tumor-level biological correlates remain poorly defined. We used tumor transcriptomics to identify pathways associated with patient-reported stress and depression symptoms. Methods: RNA sequencing was conducted on FFPE tumor samples in 195 women with stage I-III BC (152 ER+, 43 ER–) from the Women’s Health after Breast Cancer cohort. At diagnosis, participants completed Perceived Stress Scale (PSS-10) and Center for Epidemiologic Studies Depression (CES-D) Scale. High-low stress (PSS-10 >14 vs 0-14) and high-low somatic symptoms (CES-D somatic > 3 vs ≤ 3) were defined. Differential expression and gene-set enrichment analyses compared high-stress/low-somatic-symptom (HS/LSS) and low-stress/high-somatic-symptom (LS/HSS) groups with low-stress/low-somatic-symptom controls, stratified by estrogen receptor (ER) status, adjusted for age and education. Caris Life Sciences CODEai evaluated overall survival (OS) from tissue collection to last contact. Results: In ER+BC, HS/LSS showed increased humoral-immune activity and checkpoint signatures, with reduced neuroendocrine activation. LS/HSS enriched for a neuroendocrine state, ribosome biogenesis, immune and cell-cycle pathways, with loss of epithelial regulatory programs. In ER– BC, HS/LSS showed growth-factor-driven proliferation with reduced epithelial differentiation and greater immune-checkpoint engagement. LS/HSS exhibited metabolic-stress features with loss of epithelial/immune programs and increased keratinization, consistent with impaired antigen presentation and altered differentiation. Table outlines key up- and down-regulated signatures. Using CODEai, in ER+ (n=11309), higher PHOX2A (41 m vs 38.4 m) and TDGF1 ( 42 m vs 37.4 m), and in ER– (n=6402), higher SCL5A11 (24 m vs 20.7 m) and KRT40 (23.5 m vs 21.1 m) were associated with better OS, all p < 0.01. Conclusions: Patient-reported stress and depressive somatic symptoms map to distinct ER-specific tumor transcriptional signatures involving immune regulation, proliferation, metabolism and differentiation. Concordant survival associations support potential clinical relevance and warrant validation to identify actionable targets. ER+ ER– HS/LSS Genes (log 2 FC) Up IGLV3-16 (3.3) , IGHV3-30 (2.5) IGF2 (4.2) Down CHGA (–21.5) KRT40 (–18.4) , PADI3 (–24.1) Pathways (NES) Fcγ-receptor (2.7), B-cell receptor (BCR) (2.7), PD-1 co-inhibition (2.1) PD-1 co-inhibition (2.4), MHC-I (2.1), ribosome (–2.1) LS/HSS Genes (log 2 FC) Up PCSK1 (4.0) IGFBP1 (7.6), HSD11B1 (4.6), OSGIN2 (3.0) Down PHOX2A (–6.0) , TDGF1 (–5.4) IGHV7-4-1 (–18.9) , MUC2 (–21.5) , SLC5A11 (–21.1) , PADI3 (–22.3) Pathways (NES) Ribosome biogenesis (3.1), IFNα (2.7), G1/S (2.7), G2/M (2.6), BCR (2.6) Keratinization (2.7), cornified envelope (2.3), antigen presentation (–1.8), G1/S (–1.7)

Evaluating and validating immune effector dysfunction as a biomarker in bladder cancer.

e16601 Background: Checkpoint inhibitors (CPI) have transformed bladder cancer treatment, yet response rates remain limited. Molecular subtypes provide prognostic information, but response to immunotherapy varies within subtypes. T-cell exhaustion and senescence represent biologically distinct mechanisms of immune effector dysfunction (IED) that may limit CPI efficacy. A 172-gene transcriptomic IED score (IED172) was previously derived and validated in acute myeloid leukemia and melanoma. We hypothesized that IED172 would demonstrate cross-tumor validity as a prognostic biomarker in bladder cancer. Methods: We analyzed bulk-RNA sequencing data from three independent cohorts: TCGA-BLCA, IMvigor210 (phase 2 single arm trial of atezolizumab in metastatic urothelial carcinoma), and an institutional Baylor College of Medicine (BCM) cohort with matched proteomic profiling. Patient-specific transcriptomic and proteomic IED172 scores were derived from the mean expression of 172 genes and 122 constituent proteins, respectively. An IED Prognostic Index (IED-PI), a weighted combination of LASSO-selected genes, was used to stratify patients into high and low groups based on median IED-PI for survival analysis. Statistical analyses included Kruskal-Wallis, Kaplan-Meier, univariate and multivariate Cox regression. Results: We analyzed 406 patients from TCGA-BLCA, 348 from IMvigor210, and 60 from BCM. Transcriptomic IED172 scores varied significantly across molecular subtypes in TCGA-BLCA (p = 7.97x10⁻²²), BCM cohort (p = 0.014) and IMvigor210 (p = 3.2x10 -15 ). In TCGA-BLCA, luminal infiltrated exhibited the highest median IED172 score (7.19), while luminal papillary tumors had the lowest (5.9). This pattern was reproduced in both the BCM cohort and IMvigor210. In BCM cohort, transcriptomic and proteomic IED172 scores were strongly correlated (R = 0.75; p = 1.4x10⁻⁶). In TCGA-BLCA, high IED-PI was associated with inferior median progression-free survival (18.2 vs 55.2 months; p < 0.0001) and overall survival (OS) (20.2 vs 92.9 months; p < 0.0001) compared to low IED-PI. In multivariate Cox regression adjusting for stage, grade, and molecular subtype, IED-PI remained independently prognostic (HR 4.93; 95% CI 3.19-7.63; p < 0.001). In IMvigor210, high IED-PI was associated with inferior median OS compared to low IED-PI (6.7 vs 16.0 months, respectively; p < 0.0001). Conclusions: IED172 demonstrates cross-tumor validity in bladder cancer, stratifying tumors by molecular subtype with orthogonal transcriptomic-proteomic validation. The consistent prognostic significance across both CPI-treated (IMvigor210) and non-CPI-treated (TCGA-BLCA) cohorts suggests IED-PI identifies patients with inherently aggressive disease. Establishing predictive value for CPI response would require demonstrating a treatment-by-biomarker interaction in randomized data comparing CPI to non-CPI treatment.