Browse Articles

Basic palliative care assessments in the treatment of urological oncology patients: A prospective cross-sectional study.

e24069 Background: Current guidelines on palliative care in oncological patients recommend assessing physical, psychological, social, and spiritual needs as well as distress and information needs of patients and relatives. A validated tool frequently used for this purpose is the Edmonton Symptom Assessment Scale (ESAS). The MIDOS2 questionnaire is the validated German version of the ESAS. Though validated in cancer patients (pts) in general, the MIDOS2 has not yet been validated specifically in uro-oncological patients. Methods: Uro-oncological pts receiving systemic cancer therapy at a single academic center were enrolled in this prospective cross-sectional study. After consent, patients were screened with MIDOS2 as well as the Distress Thermometer (DT), G8 Questionnaire (G8), 6-Item Screener (SIS) and Mini Nutritional Assessment (MNA). Repeated screening was performed after 3 months (T3). Epidemiological and clinical data collected as well. Using the MIDOS2 cut-off of ≥8 points indicating need for palliative support, patients were grouped and DT, G8, 6IS and MNA results compared. MIDOS2 sum scores were additionally analyzed across tumor entities. Descriptive statistics, ANOVA, Mann–Whitney U, and Pearson/Spearman correlations were applied. Results: From 04/2025-01/2026, 133 patients were included (median age: 65 y, 119 male, 43 prostate cancer, 37 urothelial carcinoma, 24 renal cell carcinoma, 29 other). Comparing pts with low (0-7 points, n = 86) and high (³8 points n = 47) symptom burden values, DT (p = 0,002) MNA (p < 0,001) and G8 (p < 0,001) results were more frequently pathological in the high burden group. No significant correlation was found for the SIS. Symptom burden as assessed by MIDOS 2 was highest in weakness (mean 1,23) and lowest in vomit (mean 0,17). At data cut-off, 86/133 pts had assessments at T0 and T3 months (43/53 pts with T0 at any time of treatment, 43/80 pts with T0 before start of treatment). Comparing assessment at T3 to T0, 12 pts improved from the high to low symptom burden group, and 12 pts impaired regarding symptom burden, while 62 pts had no change. Comparing reassessment between pts tested at any time of treatment and tested before and after initiation of treatment, differences in improving and impairing rates were not observed. When analysing DT, MNA and G8 scores, improvement was more frequently observed. SIS remained unchanged. Conclusions: Uro-oncological pts often experience symptom burden detectable by MIDOS2, influenced by cancer type, treatment and patient-related factors. MIDOS2 total scores of 8 points or higher indicate further stress for the patient and should lead to the initiation of specialized palliative care. As symptom burden may vary during patient history, even within a limited time frame, repeat testing is reasonable.

Proton beam therapy versus interventional procedures for hepatocellular carcinoma: A systematic review and meta-analysis of comparative studies.

e16280 Background: Proton beam therapy (PBT) is increasingly used for hepatocellular carcinoma (HCC) due to its dosimetric advantages and potential for liver function preservation. However, its comparative effectiveness versus interventional modalities such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) remains incompletely defined. Methods: A systematic search of PubMed and Web of Science (October 14, 2025) identified comparative studies evaluating PBT versus interventional procedures for HCC. Eligible studies included randomized and comparative observational studies reporting clinical outcomes. Random-effects meta-analyses were performed for overall survival (OS) and local control (LC). Toxicity profiles were compared between treatment modalities. Risk of bias was assessed using ROB-1 and ROBINS-I. Results: Six studies (2 randomized, 4 retrospective) comprising 1,625 patients (315 PBT, 1,310 interventional) met inclusion criteria. Comparator modalities included TACE, RFA, or combined approaches. PBT dose ranged from 66 to 80.5 GyE delivered in 10–38 fractions. Meta-analysis of five studies demonstrated no significant difference in OS (pooled HR 1.45, 95% CI 0.82–2.56) with substantial heterogeneity (I² = 71%). In contrast, pooled analysis of four studies showed significantly superior LC with PBT (pooled HR 2.34, 95% CI 1.56–3.50, p < 0.0001) with negligible heterogeneity (I² = 0%). Progression-free survival (PFS) and recurrence-free survival (RFS), reported inconsistently, favored PBT in individual studies (PFS HR 3.62; RFS HR 1.39). Across studies, PBT preserved liver function with stable ALBI scores and markedly lower hepatic toxicity: grade ≥3 ALT/AST elevation 0% vs 10.3-18.2%, ascites 0% vs 21.2%, and hospitalization 24 vs 166 days. No grade ≥3 hepatic toxicity or treatment-related mortality occurred with PBT. Conclusions: While OS appears comparable between PBT and interventional procedures for HCC, PBT provides significantly improved LC and markedly less treated-related hepato-toxicity . These findings support PBT as a compelling non-invasive alternative to interventional therapies, particularly for patients in whom hepatic reserve is critical. Further prospective trials are warranted to clarify long-term survival benefits.

Forecasting the durability of overall survival benefit with gemtuzumab ozogamicin in acute myeloid leukemia: A cumulative and time-series meta-analysis.

e18525 Background: Gemtuzumab ozogamicin (GO) has demonstrated survival benefits in patients with acute myeloid leukemia (AML across multiple randomized trials and meta-analyses. However, whether the magnitude of this benefit remains stable as evidence continues to accumulate has not been formally evaluated. We applied cumulative and forecast meta-analytic methods to assess the temporal stability and projected durability of the overall survival (OS) benefit associated with GO. Methods: Study-level hazard ratios (HRs) for overall survival were extracted from randomized controlled trials comparing GO-containing regimens with non-GO controls. Random-effects meta-analysis was performed using restricted maximum likelihood estimation. Cumulative meta-analysis was conducted in chronological order to evaluate the evolution of pooled effect estimates over time. Time-series forecasting of cumulative pooled log-HRs was performed using automated ARIMA modeling to project future pooled estimates over a ten-year horizon. Robustness was assessed using prediction intervals and leave-one-out sensitivity analyses. Results: Three randomized trials encompassing patients treated between 2011 and 2019 were included. The pooled random-effects meta-analysis demonstrated a significant OS benefit associated with GO (HR = 0.85, 95% CI 0.78–0.92), with prediction intervals remaining below the null. Cumulative meta-analysis showed early emergence of benefit followed by stabilization of pooled HR estimates without attenuation as additional studies accrued. Forecast modeling projected sustained pooled HRs centered around 0.83–0.85 over the subsequent decade, with forecast intervals consistently excluding unity. Leave-one-out sensitivity analyses confirmed that no single study disproportionately influenced the pooled or forecasted results. Conclusions: Using cumulative and forecast meta-analysis, we demonstrate that the overall survival benefit associated with gemtuzumab ozogamicin in AML has remained stable as evidence has matured and is projected to persist under continuation of historical trends. These findings support the durability and robustness of GO’s survival advantage and illustrate the utility of forecast meta-analysis as a complementary framework for evaluating long-term evidence stability.

Non-operative management in mismatch repair deficient (dMMR) esophagogastric cancer (EGC) following immune checkpoint inhibition (ICI).

4078 Background: ICI achieves deep and durable responses in patients with dMMR and microsatellite instability-high (MSI-H) EGC, creating an opportunity for non-operative management (NOM) of localized disease. However, limited data exists regarding long-term outcomes with NOM and factors associated with ICI failure, which we evaluated in this retrospective cohort study. Methods: We identified patients with EGC managed at MSK from 2007-2025 whose tumors were dMMR by IHC or MSI-H by next generation sequencing and analyzed patient/tumor characteristics and clinical outcomes in those who received curative-intent therapy (systemic therapy and/or surgery; ICI was first introduced in 2018). Clinical complete response (cCR) was defined as the absence of disease by available clinical, radiographic, and endoscopic assessment. Results: A total of 211 patients with localized dMMR/MSI-H EGC were identified, with median follow-up of 48 months (IQR 24-77). Primary tumor sites were stomach (71%), GE junction (17%), and esophagus (12%). Among 122 patients who underwent germline testing, 15 (12%) had Lynch syndrome. Initial treatment was upfront surgery in 85 patients (40%), chemotherapy (chemo) in 68 (32%), ICI alone in 44 (21%), and chemo/ICI in 14 (7%). Among 58 patients treated with ICI +/- chemo, 27 (47%) achieved a cCR. 6 patients underwent surgery despite cCR, with pathologic complete response (pCR) rate of 4/6 (67%); pCR rate in those without cCR was 3/16 (19%), yielding an overall pCR rate of 32%, higher than the pCR rate observed with chemo alone (5/48 [10%]). 21 patients elected for NOM after cCR; among those with ≥1 year of follow-up, 16 of 17 (94%) remain alive and surgery-free at 1 year. cCR rates were similar between those receiving ICI alone (45%) and chemo/ICI (50%). Notably, 2/2 (100%) patients treated with dual ICI therapy achieved cCR. Lower cCR rates were observed in patients with shorter time on ICI therapy (5/17 [29%] with ≤3 months of ICI vs 14/30 [47%] with > 3 and < 6 months vs 8/11 [73%] with ≥6 months) and in those with clinical nodal involvement (6/17 [35%] vs 14/19 [74%] in N0); 3 patients who underwent surgery had pCR at tumor but residual nodal disease. cCR rate was also numerically lower in the 19% of patients with MMR heterogeneity, defined by focal loss of MMR proteins on IHC or discordant MMR status between tissue specimens (4/11 [36%] vs 23/47 [49%] in non-heterogeneous cases). Conclusions: In this MSK cohort, ICI induced deep responses in nearly half of patients with localized dMMR/MSI-H EGC. Patients achieving cCR who pursued NOM demonstrated excellent outcomes, with most remaining surgery-free at 1 year, supporting the viability of NOM after careful multidisciplinary review.

Evaluation of the combination of regorafenib + avelumab in patients with HPV-associated cancer: The phase II REGOMUNE study.

2517 Background: HPV-associated malignancies—including cervical, anal, head and neck, and penile cancers—form a biologically distinct group with limited responsiveness to immune checkpoint inhibitors (ICP) in monotherapy. Combining anti-angiogenic agents with immunotherapy may enhance efficacy by reshaping the tumor microenvironment. REGOMUNE explores this rationale by evaluating regorafenib plus avelumab association. Methods: REGOMUNE is a French multicenter, open-label, phase II trial assessing the combination of regorafenib (160 mg daily for 3 weeks of a 4-week cycle) and avelumab (10 mg/kg biweekly) in patients with advanced/metastatic HPV-driven solid tumors. The primary endpoint is the 6-month disease control rate (DCR) per RECIST 1.1 after central review. Secondary endpoints include overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Correlative studies will analyze baseline tumor samples to identify biomarkers of response. An exact single stage design was used testing 10% vs 25% DCR (5% type 1 error rate and 80% power), requiring ≥ 8 patients with disease control at 6 months among 40 patients to demonstrate efficacy. Results: From March 2023 and to February 2024, 44 patients were enrolled across 6 centers. Median age was 62 (range :33-80). Median follow-up was 18.3 months (95% CI : 14.9-21.1). Median number of prior treatment lines was 2 (range :0-7). Anal (41%) and cervical (32%) cancers were the predominant primary sites, with squamous cell carcinoma representing 70.5% of cases. Among 33 evaluable patients for efficacy, the 6-month DCR was 45.5% (N = 15) [90% CI : 30.5-61.1], with 12 (36.4%) partial response, 11 (33.3%) stable disease, and 10 (30.3%) progressions. Median PFS was 5.3 months (95% CI: [3.0 – 7.3]). Median OS was 15.0 months (95% CI [7.2 – 21.6]). Treatment modifications due to adverse events occurred in 33/42 (78.6%) patients. Common grade 3/4 adverse events included palmar-plantar eryhtrodysesthesia syndrome (11.9%), diarrhea (9.5%) and fatigue (7.1%). One treatment-related death was reported. Conclusions: REGOMUNE is the first phase II trial to demonstrate a clinically meaningful efficacy signal surpassing historical CPI outcomes as monotherapy with an anti-angiogenic plus immune CPI combination in patients with HPV-positive tumors. Biomarker analyses are ongoing to identify predictive signatures associated with the durable responses observed in this cohort. Clinical trial information: NCT03475953 .

Incidental breast findings identified on non-breast imaging: A multi-facility real-world analysis and implications for early detection.

e12565 Background: Breast cancer screening relies primarily on age- and risk-based criteria and dedicated breast imaging. However, breast abnormalities are frequently visible on non-breast imaging performed for unrelated clinical indications. The prevalence and clinical implications of these incidental breast findings across large health systems remain incompletely understood. Methods: Radiology reports from 93 hospitals within Lifepoint Health were retrospectively analyzed over an 18-month period. Approximately 4.9 million hospital-based imaging reports across all modalities and anatomic regions were evaluated using a validated computational linguistics (CL) model designed to identify breast and lymph node findings. Model performance was assessed through dual human annotation of over 1,000 reports, demonstrating > 96% accuracy, with a positive predictive value of 95% and negative predictive value of 97%. Identified breast findings were classified as known (dedicated breast imaging or documented follow-up) or unknown (potential incidental findings). Incidental findings were further stratified by patient age, sex, imaging modality, and anatomic region. Results: Among 4.9 million reports, 506,500 (10.3%) referenced the breast. The CL model identified 36,338 examinations (7.2%) with positive breast lesion measurements, the majority arising from mammography, breast or axillary ultrasound, or breast MRI. Incidental breast findings accounted for 4.5% of all positive breast lesions, with 86% identified on CT imaging of the neck, chest, or abdomen. A total of 1,518 patients were identified with incidental breast abnormalities. Of these, 945 (62.3%) fell within the American Cancer Society average-risk screening age range (45–80 years), while 573 (37.7%) did not meet screening criteria, including younger patients, older patients, and men. Conclusions: Incidental breast findings identified on non-breast imaging represent a definitive and under-recognized opportunity for earlier cancer detection, including among populations not captured by current screening guidelines. Following completion of this analysis, a multi-facility pilot was implemented across 59 hospitals using AI-enabled detection and follow-up technology to systematically identify incidental breast findings and re-engage patients in screening and diagnostic workflows. Through this approach, a subset of incidental findings was confirmed to represent breast cancer, including early-stage disease. These findings support the integration of systematic incidental finding detection and management into routine imaging workflows as a complementary pathway to guideline-based breast cancer screening.

Molecular subtype and survival in inflammatory breast cancer: A contemporary population-based analysis.

e13088 Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer with persistently poor outcomes. Although prior population-based studies have demonstrated prognostic heterogeneity by hormone receptor and HER2 status, much of the existing evidence is derived from relatively small cohorts and earlier treatment eras. As treatment paradigms have evolved, updated analyses using large, contemporary population-based datasets are needed to better characterize survival patterns across receptor-defined subtypes. Methods: We conducted a retrospective population-based cohort study using Surveillance, Epidemiology, and End Results (SEER) data from 2000–2020, including patients diagnosed with inflammatory breast cancer. Patients were identified using SEER criteria and required to have known estrogen receptor (ER), progesterone receptor (PR), and HER2 status for molecular subtype classification. Tumors were categorized as HR+/HER2–, HR+/HER2+, HR–/HER2+, or triple-negative. Overall survival was defined as time from diagnosis to death from any cause or last follow-up. Survival was evaluated using Kaplan–Meier methods with log-rank testing and multivariable Cox proportional hazards models adjusted for demographic, socioeconomic, clinicopathologic, and treatment-related factors. Analyses were conducted using complete-case data. A study protocol was developed prior to analysis and reviewed by faculty collaborators. Results: The study cohort included 5,920 patients with inflammatory breast cancer. Overall survival differed significantly by molecular subtype (log-rank p < 0.0001). In multivariable analyses, triple-negative disease was associated with significantly worse overall survival compared with HR+/HER2– tumors (HR 1.65, 95% CI 1.54–1.77), whereas HR+/HER2+ tumors demonstrated improved survival (HR 0.66, 95% CI 0.54–0.80). In contrast, survival among patients with HR–/HER2+ tumors did not differ significantly from the reference group. Receipt of chemotherapy was independently associated with improved overall survival (HR 0.61, 95% CI 0.56–0.67). Conclusions: In this large contemporary population-based analysis, molecular subtype remained a major determinant of prognosis in inflammatory breast cancer. Triple-negative disease was associated with substantially poorer survival, while HER2-positive tumors, particularly those that were hormone receptor–positive, demonstrated more favorable outcomes. These findings confirm and extend prior population-based analyses by providing stable, modern-era estimates of subtype-specific survival in IBC, and may inform prognostic counseling and subtype-specific treatment considerations.

Real-world outcomes of bispecific antibodies in relapsed/refractory (R/R) follicular lymphoma (FL).

7010 Background: Mosunetuzumab (mosun) and epcoritamab (epco) are bispecific antibodies (BsAbs) approved for R/R FL, with pivotal trials (n=90-128) initially demonstrating 60-63% complete response rate (CRR), 80-82% overall response rate (ORR), and 1-year progression-free survival (PFS) rate of 58-66%. Real-world outcomes remain limited. We report the real-world efficacy and safety outcomes of BsAbs for patients (pts) with R/R FL treated in the Collaborative United States Bispecifics Consortium (CUBIC). Methods: This is a multicenter retrospective study of adult pts with R/R FL treated with standard of care mosun or epco between 2/2023 and 9/2025 at eight CUBIC centers. Efficacy outcomes included ORR, CRR, PFS, and overall survival (OS). PFS and OS were estimated using the Kaplan-Meier method. Safety outcomes included incidence and grade (G) of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Results: A total of 99 pts with R/R FL were treated with BsAb, with 92% receiving mosun (n=91) and 8% (n=8) receiving epco. Median age was 68 years (range 33-101), 61% were ≥65 years (n=60), 63% were male (n=62), 8% Hispanic (n=8), 92% (n=79) had ECOG performance status (PS) of 0-1, 51% (n=42) had FLIPI ≥3, and 31% (n=30) had elevated LDH. Median prior lines of therapy were 3 (range 1-14), and 15% (n=15) had prior CAR-T. Among 96 pts with complete response data, the ORR was 87% and CRR was 72%. Median time to best response was 2.9 months (mo) (range 1.2-12.7). Response rates were not significantly associated with BsAb, ECOG PS, FLIPI, elevated LDH, or prior CAR-T. At median follow-up of 16.9 mo, the one-yr and 18 mo PFS rates were 72% (95%CI 62-83%) and 56% (95%CI 45-70%). One-yr and 18 mo OS rates were 94% (95%CI 90-99%) and 92% (95%CI 86-99%), respectively. Hispanic pts had better PFS than non-Hispanic pts (2-yr PFS 100% vs 42%, p=0.02). PFS was not significantly influenced by BsAb product, elevated LDH, ECOG PS, FLIPI, or prior CAR-T. Patients with ECOG of 2 had inferior OS than pts with ECOG of 0-1 (2-yr OS 43% vs 89%, p=0.02). Male sex was associated with inferior OS compared to female sex (2-yr OS 76% vs 100%, p=0.02). No differences in ORR, CRR, PFS, or OS were observed between pts <65 vs ≥65 yrs or <80 vs ≥80 yrs. Of 96 pts with complete safety data, CRS occurred in 34% of pts (G1 26%; G2 6%), with no ≥G3 events. ICANS occurred in 3% of pts (n=3), all G1 events. The incidence of CRS or ICANS was not significantly associated with age, LDH, ECOG, FLIPI, or prior CAR-T. Conclusions: In this diverse, heavily pretreated real-world cohort, 61% of patients were aged ≥65 years. Bispecific antibodies for R/R FL demonstrated high response rates, favorable survival outcomes, lower rates of cytokine release syndrome—primarily due to fewer grade ≥2 events—and ICANS rates comparable to those observed in pivotal clinical trials, supporting their use across heterogeneous populations, including very elderly patients.

Racial/ethnic and age-related disparities in contralateral breast cancer risk among survivors: SEER MP-SIR analysis (2000–2022).

e12698 Background: Contralateral breast cancer (CBC) is a persistent survivorship risk, with prior SEER data showing elevated rates in non-White groups unexplained by socioeconomic factors. Contemporary intersectional disparities (age + race/ethnicity) are understudied. Methods: Using SEER 17 registries (Incidence - SEER Research Data, 17 Registries excl. AK, Nov 2024 Sub [2000–2022]), we identified 1,090,902 women with first primary invasive breast cancer. MP-SIR sessions calculated standardized incidence ratios (SIRs) and absolute excess risks (AER per 10,000 person-years) for metachronous CBC (latency ≥2 months), stratified by race/ethnicity, age, and latency. Results: 39,408 CBC events occurred (overall SIR 1.33). Non-White survivors had higher risks vs. White (SIR 1.11): Black 1.44, American Indian/Alaska Native 1.87, Asian/Pacific Islander 1.51 (all p < 0.05), with amplified AER. Disparities were most pronounced in young women (e.g., ages 20–24: Black SIR 15.83 vs. White 8.69) and persisted long-term (≥10 years: Black 1.58, AI/AN 2.17 vs. White 1.19; all p < 0.05). These extend prior SEER findings of higher 25-year CBC cumulative incidence in Black women (~12.7% vs. 9.7% White). Conclusions: Young non-White survivors, particularly Black women, experience markedly higher and enduring CBC risks with greater absolute burden. Persistent disparities warrant tailored lifelong surveillance and equity-focused interventions in survivorship care.

Regularized regression in ultra-small chemometric datasets: A methodological case study using FTIR spectra of Schiff bases

This study is not intended to establish a predictive framework for reaction yield. Instead, it is framed as a methodological investigation examining the statistical behavior and instability of regularized regression techniques when applied to ultra-small, high-dimensional chemometric datasets. The analysis is based on a curated dataset of Schiff base compounds ( n  = 21) for which post-synthesis Fourier Transform Infrared (FTIR) spectra and experimentally reported reaction yields are available. Structural information for all compounds is fully disclosed to ensure chemical transparency. Descriptive physicochemical properties, including molecular weight, physical appearance, retention factor (Rf), melting point, and reaction yield, are summarized to characterize the dataset; however, only yield (%) is used as the response variable in the subsequent statistical analyses. Baseline-corrected and normalized FTIR spectra were transformed into a high-dimensional explanatory matrix and analyzed using regularized regression approaches designed for high collinearity and p ≫ n settings, specifically sparse Partial Least Squares (sPLS) and Elastic Net regression. Model behavior was examined using leave-one-out cross-validation (LOOCV), which is more appropriate for extremely small datasets where conventional train–test splitting is unreliable. Given the severe sample-size limitation, the analysis is interpreted as a methodological illustration rather than a generalizable predictive framework. Model outputs are therefore discussed primarily in terms of coefficient sparsity, variability, and stability under regularization rather than predictive accuracy. Overall, the study demonstrates the practical challenges and statistical instability that arise when regression-based machine learning techniques are applied to ultra-small spectral datasets. The results highlight the importance of cautious interpretation and methodological transparency when chemometric models are developed under severe sample-size constraints.

Crystal quality and oxygen incorporation in ultra-high-rate GaN growth through oxide vapor-phase epitaxy

The relationship between crystal quality and growth rate, as well as the effect of growth temperature, was investigated for Gallium nitride (GaN) growth using oxide vapor-phase epitaxy under conditions of increased Ga2O flow. The Ga2O flow rate was set to approximately seven times the maximum value previously reported by our group, and the growth rate was increased by increasing the NH3 flow rate. At a growth temperature of 1286 °C, the crystal quality deteriorated with increasing growth rate. In contrast, at a higher growth temperature of 1320 °C, the crystal quality was maintained, and a maximum growth rate of 1.03 mm/h was achieved. However, the oxygen concentration also increased with increasing growth rate, and pronounced cracks and voids appeared when it exceeded 2 × 1021 cm−3, causing significant degradation of crystal quality. Notably, even at comparable growth rates, the oxygen concentration decreased with increasing growth temperature. These results indicate that high-temperature growth is effective for further enhancing the growth rate while suppressing oxygen incorporation and maintaining crystal quality, demonstrating the potential of oxide vapor-phase epitaxy for millimeter-per-hour-class bulk GaN growth.

Mathematical modeling of tumor nanomechanical fingerprints: A weighted skew-normal distribution approach for cancer diagnosis and treatment monitoring

Tendon‐Inspired, Fatigue‐Resistant Conductive Organohydrogels via Solvent‐Exchange‐Assisted Mechanical Training

ABSTRACT The hierarchical fiber architecture of tendons, which integrates high fatigue resistance, high water content, and rapid responsiveness to stimuli over millions of annual cycles, makes them an ideal model for long‐term wearable intelligent materials. However, synthetic hydrogels prepared via methods such as electrospinning, freeze–thawing, freeze–casting, and solvent exchange, often lack comprehensive structural and functional integration compared to their biological counterparts. To address this challenge, we developed a synergistic fabrication strategy that integrates freeze–thawing, mechanical training, and solvent exchange to construct hierarchically structured hydrogels. The polyvinyl alcohol‐based hydrogel that has been repeatedly freeze–thawed, was then immersed in a glycerol/water solvent containing ferric chloride and subjected to approximately 200 000 mechanical training cycles. The resulting hydrogel exhibited remarkable comprehensive properties, including a tensile strength of 9.38 MPa, a fracture energy of 187.5 kJ m −2 , a fatigue threshold of 7850 J m −2 , a conductivity of 0.64 S m −1 , and excellent flexibility even at –80°C. Leveraging this multifunctionality, the hydrogel was further assembled into a strain sensor capable of precise, rapid monitoring of finger motion and was employed in a gesture‐controlled drone system. This work provides a universal and effective approach to designing fatigue‐resistant hydrogels, offering new insights into the development of next‐generation bioinspired, flexible electronic materials.

Readiness of Zanzibar’s public health facilities to deliver NCD services: a cross-sectional survey toward UHC

Abstract Non-communicable diseases (NCDs) are a growing public health challenge, particularly in low- and middle-income countries (LMICs), where weak health systems limit access to effective care. Achieving Universal Health Coverage (UHC) requires health facilities that are equipped and ready to deliver NCD services. However, evidence on the readiness of health facilities to provide these services in various contexts is limited. This study contributes to filling this gap by assessing the availability and readiness of health facilities to provide essential NCD services in the context of Zanzibar. We employed a facility cross-sectional survey and collected data across all 52 public and parastatal health facilities in Zanzibar using an adapted WHO Service Availability and Readiness Assessment (SARA) tool, incorporating elements from the Pen Plus survey and the Access Bottlenecks, Costs, and Equity (ABCE) survey tools. We generated readiness scores across various strata and used multiple regression analysis to examine factors associated with readiness. Readiness was assessed in terms of availability of trained workforce, essential medicines, diagnostic capacity, financial risk protection mechanisms, and patient registration and follow-up systems. We found an average readiness score of 54% across all facilities, with primary health care centers having the lowest readiness score (29%) compared to the referral hospital (73%). Readiness was particularly low in diagnostic and treatment services (40%), financing and payment mechanisms (31%), and essential medicines (53%), but comparatively higher in healthcare workforce (73%) and infrastructure readiness (69%). Lower-level facilities were associated with lower readiness scores after adjusting for key confounders in the multiple regression analysis. Availability of both inpatient and outpatient care was associated with significantly higher readiness (β = 10.50, p  = 0.029). Primary health care facilities remain underprepared to deliver essential NCD services and overall readiness scores mask substantial variation by service type and facility. Strengthening service readiness will require targeted investments in workforce training, diagnostic capacity, supply chain systems, and financial protection measures to advance equitable NCD care as part of UHC efforts.

Photochemical modification of two fluorene-based molecules with DNA intercalating and anti-methicillin resistant Staphylococcus aureus activity

Cell-free DNA fragmentomics as an enabler of tumor-of-origin classification using a commercial targeted cfDNA panel.

3059 Background: Analysis of cell-free DNA (cfDNA) fragmentation patterns (“fragmentomics”) has emerged as a powerful approach for cancer detection and classification, but most prior studies rely on whole-genome or research-grade sequencing. The feasibility and performance of fragmentomics using commercial targeted cfDNA next-generation sequencing (NGS) panels used in routine clinical care remain unclear. We evaluated whether fragmentomics metrics derived from the Tempus xF targeted cancer exon panel could accurately classify tumor type. Methods: We analyzed cfDNA sequencing data from 1,950 patients across 10 cancer types sequenced on the Tempus xF clinical NGS panel (105 genes), split a priori into training (n=1,455) and validation (n=495) cohorts. Exon-level fragmentomics features were extracted, including fragment size distributions, Shannon entropy, normalized read depth, proportions of short fragments, fragment size bins, motif diversity, and chromatin-context–specific entropy metrics. Elastic-net regression models were trained to classify tumor type using 10-fold cross-validation, with area under the receiver-operating characteristic curve (AUROC) as the primary endpoint. Model performance was independently evaluated in the validation cohort, including stratification by circulating tumor DNA (ctDNA) fraction. Results: In cross-validation of the training cohort, a combined fragmentomics model achieved a median AUROC of 0.790 across cancer types. In independent validation, the combined model maintained robust performance with a median AUROC of 0.794. Prostate, breast, and ovarian cancers demonstrated the highest discrimination (validation AUROCs up to 0.952 and 0.936 for prostate and breast cancer, respectively). Performance improved substantially in samples with higher tumor burden: among validation samples with ctDNA fraction ≥10% (85.2% of cases), the median AUROC increased to 0.815 compared with 0.719 in low ctDNA samples. Conclusions: Fragmentomics analysis applied to an existing commercial targeted cfDNA panel enables accurate tumor-of-origin classification without additional sequencing or assays. These findings demonstrate a scalable strategy to extend the diagnostic capabilities of routine clinical cfDNA testing and support the integration of fragmentomics into real-world liquid biopsy workflows, particularly in patients with sufficient ctDNA fraction.

Large-scale EMR-based machine learning for early risk stratification of lung cancer.

e20015 Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection is crucial for improving outcomes; however, existing screening tools often rely on specialized data (e.g., CT imaging and biomarkers), limiting their broad implementation. We aimed to develop a machine learning model using routine clinical and demographic data from electronic health records (EHRs) to identify individuals at high risk of lung cancer up to three years before diagnosis. Methods: We analyzed 61 million EHR entries from Russian healthcare facilities, including diagnoses, vital signs, lab results, physician visits, and demographic data. Patients with confirmed lung cancer (ICD-10 C34) were matched with controls without any cancer diagnosis. . Patients were assigned to time-to-diagnosis groups (0.5–1, 1–2, and 2–3 years before diagnosis as positive; ≥3 years before diagnosis and cancer-free controls with > 3 years observation as negative). Data within 6 months prior to diagnosis and post-diagnosis periods were excluded to reduce diagnostic work-up leakage. Models (histogram-based gradient boosting, LightGBM, random forest) were trained with class rebalancing (SMOTE) and combined via a soft-voting ensemble. The dataset was split 80:20 at the patient level to prevent leakage, with additional validation of cohorts containing other malignancies (population-representative validation cohort). Results: On the test set, the ensemble achieved an accuracy of 88.02%, sensitivity of 78.8%, specificity of 78.43%, NPV of 98.2%, F1-score of 78.61%, and a ROC AUC of 0.8715. On the population-representative validation cohort, performance metrics were: accuracy 86.02%, sensitivity 79.1%, specificity 76.41%, NPV 95.2%, F1-score 77.73%, and ROC AUC 0.8335. The final model included 53 features, with the key contributors being age, patterns of healthcare utilization (e.g., primary care and surgical visits), vital signs (respiratory rate, pulse, blood pressure), routine laboratory parameters, and utilization of respiratory-related investigations (e.g., fluorography/CT chest), rather than cancer-specific markers. Conclusions: We have developed a highly accurate artificial intelligence model for the early stratification of lung cancer risk utilizing routine, nonspecific electronic health record (EHR) data. This model obviates the need for additional testing or specialized biomarkers, thereby rendering it scalable and cost-effective for screening at the population level. Its integration within primary care EHR systems could facilitate proactive referrals for low-dose computed tomography (CT) screening for individuals at high risk, potentially enhancing early detection rates and improving clinical outcomes.

Optimizing the ER cutoff: Using ER≥50% to define a distinct HER2+ subgroup characterized by low pCR rates, ADC resistance, and CDK4 dependency.

e12646 Background: While estrogen receptor (ER)-positive/HER2-positive breast cancer generally demonstrates better long-term survival than ER-negative/HER2-positive disease, it shows significantly lower rates of pathological complete response (pCR) to standard neoadjuvant HER2-targeted therapies. Currently, the optimal ER positivity cutoff for stratifying patients remains undefined. Methods: We analyzed a retrospective cohort of 741 HER2-positive patients treated with neoadjuvant chemotherapy plus dual HER2 blockade (trastuzumab and pertuzumab). Receiver operating characteristic (ROC) analysis was used to define the optimal prognostic ER cutoff. Integrated multi-omics analysis (TCGA, SCAN-B) and CRISPR dependency screening (DepMap) were utilized to elucidate biological mechanisms and identify therapeutic vulnerabilities. Results: ROC analysis identified 50% ER positivity as the optimal threshold for stratifying response. In multivariate analysis, ER≥50% subgroup was characterized by activated estrogen signaling, downregulated cell cycle pathways, and predicted resistance to taxanes and antibody-drug conjugates (e.g., T-DXd). Conversely, CRISPR screening prioritized CDK4 as a top essential survival dependency specifically in ER-positive/HER2-positive models, suggesting functional addiction to the Cyclin D1-CDK4 axis. Conclusions: An ER cutoff of 50% optimally defines a distinct, chemo-resistant luminal subgroup within HER2-positive breast cancer. These findings support a precision medicine strategy integrating CDK4/6 inhibitors with endocrine and anti-HER2 therapies for patients with ER≥50% tumors.

Chemo-immunotherapy (Chemo-ICI) versus chemotherapy (Chemo) alone as a first-line therapy (1L) in extensive-stage small cell lung cancer (ES-SCLC): An individual patient data (IPD)–based synthetic meta-analysis from randomized control trials (RCTs).

e20164 Background: SCLC is an aggressive high-grade neuroendocrine cancer with a high propensity for early metastasis, often leading to extensive disease on presentation. Chemo-ICI has emerged as the standard of care (SOC) for 1L ES-SCLC, though the magnitude of benefit remains uncertain and is variable across RCTs. Here, we estimate the pooled treatment effect on time-to-event outcomes using IPD from trials comparing Chemo-ICI vs. Chemo. Methods: Seven eligible phase II and III RCTs were identified through a literature search using PubMed and EMBASE. Trials (both negative and positive) evaluating first-line anti-PD-1/PD-L1 in combination with Chemo vs. Chemo alone for ES-SCLC were included. All included trials had available Kaplan-Meier (KM) plots for reconstruction of IPD using the IPDfromKM R package. We reconstructed synthetic KM curves and compared progression-free survival (PFS) and overall survival (OS) for IPD using the log-rank test and estimated HRs using the Cox model. All analyses were performed in R v 4.4.1. Results: Of the 3,057 eligible patients, 1,623 received Chemo-ICI, while 1,434 received chemotherapy alone. For PFS, Chemo-ICI showed a higher median PFS of 6.1 months (95% CI: 5.9-6.3) vs. Chemo [5.4 months (95% CI: 5.3-5.5); HR of 0.65 (95% CI: 0.59-0.7; p < 0.0001 )]. At 12 months, the estimated PFS probability was 20.3% in the Chemo-ICI cohort and 6.4% in the Chemo cohort. At 24 months, the estimated PFS probability was 11.6% in the Chemo-ICI cohort and 2.2% in the Chemo cohort. For OS, Chemo-ICI showed a higher median OS of 15.9 months (95%CI: 14.2-16) vs. Chemo of [12.1 months (95%CI: 11.2-12.2); HR of 0.72 (95%CI: 0.66-0.79; p < 0.0001 )]. At 12 months, the estimated OS probability was 62.8% in the Chemo-ICI cohort and 50.2% in the Chemo cohort. At 24 months, the estimated OS probability was 29.1% in the Chemo-ICI cohort and 20.3% in the Chemo cohort. Conclusions: To the best of our knowledge, this is the most comprehensive synthetically generated IPD meta-analysis to date, comparing Chemo-ICI with Chemo alone in the first line setting for ES-SCLC. Our analysis shows that first-line Chemo-ICI provides statistically significant but modest improvements in PFS and OS over chemotherapy alone in ES-SCLC, with durable benefit confined only to a small subset of patients. These findings highlight the need for predictive biomarkers to guide patient selection for first line Chemo-ICI while minimizing toxicity in patients with ES-SCLC.

Clinical outcomes of patients with TP53 pathway alterations by treatment type: The MD Anderson Cancer Center IMPACT 2 study.

3152 Background: TP53 pathway alterations are found in over 50% of human cancers, with variable frequency across tumor types. They are associated with aggressive tumor biology, increased metastatic potential, and poor prognosis. Herein, we report the clinical outcomes of patients with TP53 pathway alterations treated in the IMPACT 2 study (2014-2023; NCT02152254). Methods: Patients with advanced cancer underwent tumor biopsy and molecular profiling (CLIA-certified lab). Pathway analysis was conducted using the maftools R package. TP53 pathway alterations were defined as those involving the TP53 , ATM , CHEK1 , CHEK2 , MDM2 , and MDM4 genes. Patients were treated on clinical trials with investigational agents that included matched targeted therapies (MTTs) when available. MTT included anti-vascular endothelial growth factor (VEGF) targeted therapy, as previously published (PMID: 27466356). We analyzed the following outcomes by treatment type (MTT vs. non-matched targeted therapy [NTT] and immunotherapy [IO] vs. non-IO): objective response rate (ORR; complete response + partial response), clinical benefit rate (CBR; ORR + stable disease≥4 months), progression-free survival (PFS), and overall survival (OS). Results: Of 491 treated patients with targetable alterations, 278 (56.6%) had p53 pathway alterations (median age, 60.1 years [range, 20.5-81.7]; female, 51.4%; ECOG performance status 1, 86.0%; median number of prior therapies, 3 [range, 0-11]; liver metastases, 42.2%; >2 metastatic sites, 36.0%; high lactate dehydrogenase level, 41.0%; low albumin level, 9%). The most common tumors were colorectal (21.2%), sarcoma (13.7%), other gastrointestinal (12.2%), and breast (8.6%). Immune markers included PD-L1≥1%, 47.3% (78/165); MSI-H, 1% (2/199); and TMB-H, 10.5% (19/181). Concomitant pathway alterations were RTK-RAS (48.6%), PI3K (24.8%), and cell cycle (38.1%) pathways. MTT included VEGF/VEGFR inhibitors, N=57; MDM2 inhibitors, N=4; and TP53 activator, N=1. Clinical outcomes are shown in the Table. Conclusions: Median OS was significantly longer in patients with TP53 pathway alterations treated with IO compared with non-IO regimens. Considering the limited availability of TP53-targeted agents, no differences in clinical outcomes were noted for MTT compared with NTT. Further analyses are warranted to elucidate the molecular substrates underlying immunotherapy benefit. Clinical trial information: NCT02152254 . All patients MTT NTT P IO Non-IO P N=278 N=62 N=216 N=69 N=209 ORR 18/247 4/59 14/188 1.00 9/64 9/183 0.024* % 7.3 6.8 7.4 14.1 4.9 CBR 142/247 37/59 105/188 0.37 43/64 99/183 0.87 % 57.5 62.7 55.9 67.2 54.1 Median PFS, months 3.75 5.52 2.93 0.11 4.37 3.19 0.46 95% CI 2.89, 4.8 4.67, 8.19 2.5, 4.14 2.73, 5.56 2.66, 4.08 Median OS, months 7.99 9.01 7.3 0.96 10.85 6.9 0.024 95% CI 6.18, 9.3 7.17,12.36 5.69, 9.24 7.86, 17.42 5.65, 8.65 *Not significant after multiple testing correction (threshold α = 0.0125).