Browse Articles

Body composition metrics and clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–PSMA-617.

241 Background: Lutetium-177 ( 177 Lu)–PSMA-617 is a radioligand therapy that can improve outcomes for patients with mCRPC; however, responses are variable. We assessed the prognostic value of body composition metrics for patients treated with 177 Lu–PSMA-617. Methods: We conducted a retrospective review of 163 patients with mCRPC treated with 177 Lu–PSMA-617 at the Emory Winship Cancer Institute. The computed tomography (CT) component of baseline prostate-specific membrane antigen positron emission tomography-CT before initiation of 177 Lu–PSMA-617 therapy was analyzed with Slice-O-Matic software (version 5.0). Univariate and multivariate Cox proportion models were used to assess survival outcomes. Results: Median patient age was 73 (IQR: 65-80); 84% of patients had been treated with taxane-based chemotherapy. Median overall survival (OS) was 15 months (95% CI: 13-22), median progression-free survival (PFS) was 6 months (95% CI: 5-8), and 55% of patients had a reduction in prostate-specific antigen ≥50% (PSA50). Body mass index (BMI) decline during treatment was independently associated with an increased risk of disease progression and a 2.35-fold increased hazard of death on multivariate analysis (PFS HR=1.75, 95% CI=1.06-2.91, p=0.03; OS HR=2.35, 95% CI: 1.08–5.09, p=0.03). The associations between body composition metrics and PSA50 response, PFS, and OS on multivariate analysis that controlling for patient age, race, prior taxane use, number of prior lines of therapy, and baseline PSA are displayed in Table 1. Conclusions: A decline in BMI during treatment with 177 Lu–PSMA-617 is associated with shortened PFS and OS. Higher visceral adipose tissue index (VATI)/subcutaneous adipose tissue index (SATI) is associated with shortened OS, while higher SATI/skeletal muscle index (SMI) is associated with prolonged survival. Higher SATI, SMI, and BMI displayed a trend towards improved outcomes. Association of body composition metrics and PSA50 response, PFS, and OS in patients treated with 177 Lu–PSMA-617. Body Composition Metric N PSA50 Odds Ratio (95% CI), p PFS Hazard Ratio (95% CI), p OS Hazard Ratio (95% CI), p Baseline BMI <25 0.28 (0.10-0.78) p=0.015* 1.15 (0.69-1.93) p=0.592 1.98 (0.94-4.17) p=0.073 >25 and <30 0.45 (0.17-1.16) p=0.099 1.05 (0.64-1.72) p=0.854 1.49 (0.7-3.17) p=0.3 >30 - - - SATI/SMI >1.62 1.40 (0.68-2.88) p=0.356 0.87 (0.58-1.30) p=0.493 0.50 (0.28-0.89) p=0.019* <1.62 - - - VATI/SATI >0.64 0.78 (0.38-1.64) p=0.519 1.36 (0.89-2.07) p=0.157 2.62 (1.34-5.11) p=0.005* <0.64 - - - VATI >38.5 0.81 (0.38-1.71) p=0.58 1.54 (1.00-2.39) p=0.052 1.42 (0.77-2.63) p=0.263 <38.5 - - - SATI >1.62 1.45 (0.68-3.09), p=0.333 0.87 (0.58-1.30) p=0.493 0.57 (0.32-1.02) p=0.06 <1.62 - - - SMI >47.4 2.59 (0.97-6.91), p=0.058 0.71 (0.42-1.21) p=0.212 0.51 (0.23-1.13) p=0.097 <47.4 - - -

Real-world comparative effectiveness of first-line (1L) cabozantinib (C) versus cabozantinib with nivolumab (C+N) in patients (pts) with metastatic papillary renal cell carcinoma (mPRCC).

461 Background: mPRCC is the most common non-clear cell renal cell carcinoma (RCC). Standard of care options include both C and C+N (NCCN Guidelines V1.2026) due to a lack of randomized clinical trial results in this setting and are currently being investigated in SWOG PAPMET2 (NCT05411081). Herein, we aimed to evaluate the comparative effectiveness of C versus C+N in pts with mPRCC using a large, real-world database. Methods: This is an IRB approved retrospective study using the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: pts with mPRCC who received 1L treatment with C+N or C monotherapy from 4/29/2017 - 7/16/2024. Pts were classified into two groups based on treatment with C+N or C. Endpoints: real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS), summarized via Kaplan-Meier survival estimates and their 95% confidence intervals (CIs) and compared in the context of propensity score (PS) matching weighted analysis with the Cox proportional hazard model. The PS was constructed using logistic regression with the baseline covariates: age, race-ethnicity, gender, region, socioeconomic status, practice type, insurance, smoking status, prior nephrectomy, IMDC risk score, and 1L start year. Results: Of the 13,909 pts in the enhanced cohort, 115 pts with mPRCC were eligible and included (65 pts: C and 50 pts: C+N). The median rwTTNT for C was 6.4 months (mo) (95% CI 5.2-11) vs 11 mo (95% CI 8.4-23) for C+N (hazard ratio [HR] 0.70, 95% CI 0.45-1.08, p = 0.11). The median rwOS for C was 19 mo (95% CI 13-31) vs 27 mo (14-not reached [NR]) for C+N (HR 0.92, 95% CI 0.56-1.52, p = 0.8). After PS matching weighting, the median rwTTNT for C was 6.4 mo (95% CI 4.9-14) vs 16 mo (11-NR) for C+N (HR 0.51, 95% CI 0.28-0.92, p = 0.027). After PS matching weighting, the median rwOS for C was 20 mo (95% CI 11-44) vs 26 mo (95% CI 16-NR) for C+N (HR 0.87, 95% CI 0.45-1.69, p = 0.7). Conclusions: In this study of pts with mPRCC following PS matching weighting analysis, 1L C+N was associated with improved rwTTNT as compared to C monotherapy. However, there was no evidence of significant difference in rwOS between both groups. These hypothesis generating data need prospective validation in ongoing PAPMET2 trial. Limitations include lack of randomization, potential selection bias, and residual confounding.

Influence of radiation on green-synthesized AgNPs and their role in enhancing fluoride stress tolerance in rice

Abstract Fluoride stress severely impairs the growth and productivity of economically important crops, including rice, resulting in significant yield losses and threatening agricultural sustainability. Enhancing crop resilience requires strategies that balance plant development and stress responses. In this study, we adopted a multi-step approach to mitigate fluoride toxicity in rice. First, soil properties—texture, organic matter, pH, and nutrient content—were analysed to guide crop recommendations and optimize yield. Second, silver nanoparticles (AgNPs) were synthesized using a green approach with Bryophyllum pinnatum plant extract and characterized by UV–Vis spectroscopy, FTIR, SEM, XRD and DLS, confirming their structural integrity and morphological changes. Third, the interaction of radiation with B. pinnatum plant extract and AgNPs was examined, revealing higher energy absorption in the extract compared to nanoparticles. Finally, plant responses under fluoride stress were evaluated by comparing AgNP priming with conventional foliar fertilizer. AgNP treatment significantly improved germination, root and shoot length, photosynthetic pigments (chlorophyll), and antioxidant enzyme activity, resulting in enhanced growth and yield. These findings demonstrate, for the first time, that AgNP priming effectively regulates fluoride-sensitive defense pathways, offering a promising strategy for developing fluoride-tolerant crops and improving agricultural productivity under stress conditions.

From bladder to upper urinary tract: Unveiling the epidemiological dynamics of urothelial carcinoma.

677 Background: Urothelial carcinoma (UC), encompassing bladder cancer, ureteral cancer, and renal pelvic cancer, exhibits distinct epidemiological patterns. Bladder cancer is the most prevalent, accounting for 3.1% of all cancer cases globally, while upper tract urothelial carcinoma (UTUC) remains rare. Methods: This population-based study utilized cancer registry data from the Cancer Incidence in Five Continents (CI5) Plus database, covering 40 countries and regions between 2003 and 2017. Age-standardized rates (ASR) and age-specific incidence rates were calculated for bladder, ureteral, and renal pelvic cancers, stratified by country, sex, and year. Temporal trends were analyzed using Joinpoint regression to estimate annual percentage change (APC) and average annual percentage change (AAPC). Socio-Demographic Index (SDI) data were used to examine associations between socioeconomic development and UC burden. Results: In 2017, the ASR for bladder cancer among men ranged from 2.40 per 100,000 person-years in the Philippines to 35.69 per 100,000 in Italy. For women, ASRs ranged from 0.81 per 100,000 in Uganda to 7.98 per 100,000 in Denmark. The ASRs for renal pelvic cancer ranged from 0.01 per 100,000 in India to 1.46 per 100,000 in Japan for men and from 0.02 per 100,000 in India to 1.88 per 100,000 in Iceland for women. For ureteral cancer, ASRs in men ranged from 0.07 per 100,000 in India to 1.16 per 100,000 in Japan, while in women, they ranged from 0.06 per 100,000 in India to 0.41 per 100,000 in Estonia, Japan, and South Korea. The ASRs for all measures of urothelial carcinoma burden were higher for men than for women. From 2003 to 2017, bladder cancer ASRs declined in most developed countries but rose in Japan, Canada and developing countries. Conversely, ASRs for ureteral and renal pelvic cancers increased globally, except in the USA, Norway, Australia, and Thailand, where declining trends were observed. Age-specific incidence rates for all UC types generally increased with age. A significant correlation was noted between UC burden and SDI, with higher incidences associated with greater socioeconomic development. Moreover, for China, South Korea and Japan, UTUC accounts for 15.6%–21.8% of urothelial carcinomas, a proportion higher than that observed in other countries with similar SDI levels. Conclusions: Substantial geographic and socioeconomic disparities exist in UC burden. While bladder cancer incidence is decreasing in most developed countries, it is rising in developing regions. UTUC remains rare but shows a global increase. The relatively high incidence of UTUC in Eastern Asian warrants attention, and the underlying causes require further investigation. These patterns underscore the influence of socioeconomic development on UC epidemiology and highlight the need for tailored strategies to address regional disparities.

Stiff to Soft: A Protein‐Based Buffer Layer for Improving the Long‐Term Performance of Microneedle Sensors

ABSTRACT Long‐term monitoring of electrolyte dynamics is essential for managing chronic diseases. Conventional diagnostic tests are steadily evolving toward greater convenience, personalization, and accuracy, while wearable microneedle sensors offer a compelling alternative. However, their long‐term biocompatibility is hampered by the mechanical stiffness required to penetrate the skin. Here we report a crosslinking–recombination bovine serum albumin (CR‐BSA) coating that undergoes a unique stiff‐to‐soft transition, reconciling insertion capability with tissue compatibility. For Na + sensing, CR‐BSA serves as a functional buffer layer, delivering high sensitivity (70.6 µA/decade) and stability for more than 14 days, while significantly reducing inflammation and fibrosis compared with commercial Nafion coatings. CR‐BSA–coated microneedle sensors achieve reliable continuous monitoring of both acute and chronic hyponatremia and hypernatremia for over five days. This stiff‐to‐soft coating strategy overcomes a central barrier to microneedle sensor integration, advancing the prospects of long‐term, minimally invasive electrolyte monitoring for chronic disease management.

Modernizing biomolecular NMR: The POKY suite

Radiation dose tailoring guided by enhanced targeting (RadTARGET): A multi-center randomized controlled trial.

TPS409 Background: Definitive radiation therapy for localized prostate cancer with dose intensification and/or focal boosting has excellent oncologic outcomes. However, many patients experience long-term toxicity. Given the long-term survivorship after definitive prostate cancer treatment, there is interest in identifying strategies that can improve the therapeutic ratio of definitive radiation therapy by minimizing toxicity while maintaining excellent oncologic outcomes. Patterns of failure analyses demonstrate that intraprostatic recurrence after definitive radiation therapy occurs nearly always at the site of the primary tumor and that dose to the site of the primary tumor is an important predictor of future failure. Advanced MRI and PSMA PET/CT permit accurate discrimination of tumor from benign prostatic tissue, allowing for the possibility of concentrating radiation dose to the tumor while de-escalating dose to the uninvolved prostate gland. This strategy also lowers the dose to neighboring organs (i.e. rectum, bladder), potentially reducing rates of acute and late adverse events and minimizing the impact of prostate cancer treatment on quality of life. A randomized trial is required to compare the efficacy and toxicity of tumor-focused radiation therapy to that of standard radiation therapy for definitive treatment of localized prostate cancer. Methods: The RadTARGET trial (NCT06990542) is an investigator-initiated, multi-center, prospective, single-blind, pragmatic, two-arm randomized phase II study where patients with intermediate- or high-risk localized prostate cancer planning to undergo definitive radiation therapy with curative intent are randomized to either standard dose radiotherapy or image-guided tumor-focused radiotherapy. Patients with biopsy-proven intermediate- or high-risk localized prostate cancer with lesion visible on prostate MRI and/or PSMA PET/CT (with concordant pathology from biopsy needle locations) are eligible. This trial aims to include 150 patients randomized to one of the two arms in a 1:1 ratio via dynamic allocation to balance risk group, fractionation, intended duration of androgen deprivation therapy, bladder filling protocol, and intended spacer use. The primary endpoint is physician-reported acute any attribution genitourinary (GU) or gastrointestinal (GI) grade ≥2 toxicity within 3 months post-radiation therapy. Key secondary endpoints are radiation attribution acute GU/GI toxicity, any and radiation attribution late GU/GI toxicity, patient-reported urinary and bowel quality of life, biochemical recurrence-free survival, local failure rate, regional and/or distant metastasis-free survival (dMFS), and overall survival. RadTARGET has enrolled approximately 10% of planned patients. Clinical trial information: NCT06990542 .

Cadonilimab plus lenvatinib in advanced renal cell carcinoma: Interim analysis of a prospective, multi-cohort phase II study.

501 Background: Renal cell carcinoma is a common urological malignancy with poor prognosis in advanced stages, creating a pressing need for effective treatments. Immune checkpoint inhibitors combined with anti-angiogenic targeted therapies have demonstrated synergistic efficacy in advanced RCC. Cadonilimab, a PD-1/CTLA-4 bispecific antibody, and lenvatinib, a multi-target tyrosine kinase inhibitor, form the investigational combination in this study. This trial aims to evaluate the efficacy and safety of this dual blockade in patients with advanced RCC—including both clear cell and non-clear cell subtypes—particularly in those who have progressed on prior immunotherapy or lack standard therapeutic options. Methods: This is a prospective, open-label, multi-cohort phase II trial. The study plans to enroll 46 patients, divided into two cohorts: Cohort 1 consists of patients with ccRCC who have received prior combination therapy of immune checkpoint inhibitors and targeted agents (n=28), and Cohort 2 includes treated or treatment-naïve patients with advanced non-ccRCC (n=18). Patients will receive cadonilimab (10 mg/kg, Q3W) in combination with lenvatinib (12 mg, QD) until disease progression or unacceptable toxicity. The primary endpoint is ORR, with secondary endpoints encompassing DCR, rPFS, OS, quality of life, and safety. Sample size was calculated using a Simon's two-stage design, and efficacy is assessed according to RECIST v1.1 criteria. Results: By Oct 2025, 22 patients enrolled (16 males, 6 females; median age 54). Disease staging included: T1(T1 N0-1 M1) in 2, T2(T2 N0-1 M0-1) in 7, T3(T3 N0-1 M1) in 8, T4(T4 N1 M1) in 1 and Tx(Tx N0-1 M1) in 4 patient. The cohort included 16 cases of ccRCC and 6 cases of non-ccRCC. 5 discontinued (1 lenvatinib intolerance, 4 disease progression). In 15 evaluable patients, the combination regimen demonstrated promising antitumor activity, with an ORR of 33.3% and a DCR of 100.0%. Notably, both the ccRCC subgroup (n=9) and non-ccRCC subgroup (n=6) showed identical ORR of 33.3% and DCR of 100.0%. Median follow-up was 7 months, with a 6-month PFS rate of 66.7%. Treatment-related AEs (proteinuria, hypothyroidism, anemia) were predominantly Grade 1-2 ,72.7%. No SAEs occurred, and although Grade 3 events (hypertension, proteinuria, rare irAEs) required monitoring(22.7%), tolerability was generally good, dose reductions (lenvatinib, n=3; cadonilimab, n=1) did not impact treatment continuity. Conclusions: The Cadonilimab plus Lenvatinib combination regimen demonstrates encouraging antitumor activity and a manageable safety profile in patients with advanced RCC, with promising short-term DCR. These findings support continued patient enrollment and longer-term follow-up to further evaluate survival benefits. Clinical trial information: NCC4708. Tumor treatment efficacy summary. Count Percentage（%） Evaluable Patients 15 100.0 ORR 5 33.3 DCR 15 100.0 PR 5 33.3 SD 10 66.7

Genome-wide SNP analysis reveals genetic diversity and structure of wild and cultivated olives (Olea europaea L.) in Oman

Abstract The olive ( Olea europaea L.) crop has significant cultural, nutritional, and economic importance worldwide. While its genetic diversity has been extensively studied in the Mediterranean Basin, little is known about olive germplasm in the Arabian Peninsula, including Oman, where it represents a unique environment for olive cultivation. In Oman, both wild and cultivated olives are exposed to arid conditions, which may have led to unique genetic adaptations. Leaf samples were collected from 44 olive accessions, including wild populations (MN and UT) distributed across northern and southern Oman and introduced cultivars originating from the Mediterranean Basin and cultivated in Oman, as a comparative reference. Genomic DNA was extracted and genotyping-by-sequencing (GBS) libraries were prepared and sequenced on the Illumina NovaSeq X platform. High-quality reads were aligned to the Mediterranean olive reference genome, and single-nucleotide polymorphisms (SNPs) were called, filtered for quality, and annotated to assess their genomic distribution. Genetic diversity indices, population structure (PCA, DAPC, STRUCTURE), phylogenetic relationships, analysis of molecular variance (AMOVA), pairwise Fst/PhiST, and linkage disequilibrium were calculated to evaluate variation, differentiation, and evolutionary patterns among wild and cultivated olives. After quality filtering, 167,875 high-confidence SNPs were retained. Functional annotation revealed that many variants were located in coding and regulatory regions. For linkage disequilibrium analysis, a more stringent SNP filtering scheme was applied, and genome-wide LD showed a progressive decay of r 2 with increasing physical distance. Introduced cultivars used as comparative reference genotypes exhibited moderate genetic diversity (He = 0.100–0.162) and negative or near-zero F IS values, indicating heterozygote excess likely due to clonal propagation, whereas Omani wild olive populations (MN and UT) showed markedly lower diversity (He = 0.060–0.106) and positive F IS values, reflecting reduced heterozygosity and limited gene flow. Multivariate (PCA and DAPC), STRUCTURE, and phylogenetic analyses consistently revealed strong genetic differentiation between wild and cultivated olives, with AMOVA indicating that ~ 51% of genetic variation was explained by differences among predefined groups, dominated by the contrast between wild and cultivated olives. This study provides an early genome-wide SNP analysis of Omani wild and cultivated olives. Clear genetic differentiation was observed between wild and cultivated groups, with wild populations showing distinct variation. These findings can inform future conservation and breeding efforts for olive germplasm in arid environments.

Long-term effectiveness and safety of avelumab first-line maintenance (1LM) in locally advanced or metastatic urothelial carcinoma (la/mUC): Updated systematic literature review (SLR) and meta-analysis (MA).

678 Background: Avelumab 1LM is the standard of care for patients (pts) with la/mUC without progression after 1L platinum-based chemotherapy. We assessed the long-term effectiveness and safety of avelumab 1LM based on real-world evidence (RWE). Methods: An SLR of all observational studies published in any language between 1/1/2020 and 7/11/2025 was conducted in MEDLINE, Embase, and Cochrane. Data were narratively synthesized. Landmark 12- and 24-mo progression-free survival (PFS) and overall survival (OS) rates measured from avelumab 1LM start were pooled for MA. Results: The SLR included 83 unique studies comprising >7,000 pts treated with avelumab 1LM; 65 studies (78%) were retrospective. Most studies (n=56; 67%) were based in the US and Europe. RW pts receiving avelumab 1LM were generally older than JAVELIN Bladder 100 (JB100) pts, with median age of ≥70 in 77% (36/47) of studies. Pts with an ECOG performance score of 0-1 ranged from 66-100%. Overall, 4-54% of pts had upper tract UC. The rates of liver (4-19%) and lung metastases (14-42%) in RWE were similar to those in JB100. Between 21% and 100% of pts with disease progression received second-line therapy after avelumab 1LM, of whom 24-88% (17% and 10% in 1 study each) received enfortumab vedotin. Median OS (95% CI) from avelumab 1LM start ranged from 10.6 (3.4-15.5) to 39.5 mo (13.2-65.7). In the MA, 12- and 24-mo OS rates (95% CI) from avelumab 1LM start were 74% (69-78) and 55% (46-63). Median PFS (95% CI) from avelumab 1LM start ranged from 3.3 (2.0-4.7) to 11.5 mo (6.9-16.1). In the MA, 12- and 24-mo PFS rates (95% CI) from avelumab 1LM start were 39% (36-43) and 26% (22-30). Discontinuation rates due to adverse events (AEs) and grade ≥3 AE rates were 1-21% and 0-38% (50% in 1 study), respectively (Table). Conclusions: Our review provides a comprehensive quantitative overview of RWE, which demonstrates the beneficial effect of avelumab 1LM in routine care settings, consistent with findings from JB100. No new safety concerns were observed with long-term avelumab use. These findings offer further reassurance to healthcare providers of the established role of avelumab 1LM as part of the JAVELIN Bladder regimen in optimizing treatment decisions and sequencing for pts with la/mUC. Clinical and safety outcomes with avelumab 1LM. Outcome median across studies Outcome IQR across studies JB100 (ITT; median FU, 38 mo) Avelumab duration, median, mo 5.7 4.1-7.0 5.8 (range 0.5-49.7) Median PFS, mo* 6.2 5.6-8.9 5.5 (95% CI 4.2-7.2) 12 mo PFS, % 40.8 33.6-44.9 34 24 mo PFS, % 27.2 25.3-29.5 23.4 Median OS, mo* 21.6 17.4-23.4 23.8 (95% CI 19.9-28.8) 12 mo OS, % 75.2 67-78 72 24 mo OS, % 53.2 47.7-66.8 49.8 Grade ≥3 AEs, % 6.9 5.1-15.0 54 Discontinuation due to AEs, % 9.5 7.2-13.1 14 FU, follow-up; IQR, interquartile range; ITT, intention to treat. *From avelumab 1LM start.

Electron Channeling Contrast Imaging of Ferroelastic Domains

ABSTRACT Ferroelastic phase transitions lead to the formation of ferroelastic twins, resulting in spatial inhomogeneities in the crystal structures and functional properties of ferroelastic materials. Despite the importance of such nanoscale twins in oxide heterostructures, their direct, non‐invasive observation has relied on cumbersome and low‐throughput techniques such as transmission electron microscopy and synchrotron X‐ray diffraction, or been restricted to materials with coexistence of ferroelectric and ferroelastic states, by detecting the coupled ferroelectric order. In this study, the application of electron channeling contrast imaging (ECCI) in a scanning electron microscope for imaging ferroelastic domains in various oxide heterostructures is demonstrated. These include systems where ferroelasticity is coupled with critical functional properties such as ferroelectricity, magnetism and charge transport. The versatility of this imaging method is highlighted across different heterostructure geometries, from bare thin films to multilayers, achieving an impressive resolution of 6 nm. ECCI presents a powerful approach for exploring the rich spectrum of ferroelasticity‐coupled phenomena in oxide heterostructures.

Alzheimer’s disease-linked ACE variants increase ACE1 catalytic activity and production of angiotensin II

Final overall survival results from the EORTC 1333/PEACE-3 trial: Enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer.

15 Background: In EORTC1333.PEACE-3 the combination of enzalutamide and radium-223 (ENZ/RAD) prolonged rPFS and OS (interim analysis) in patients with mCRPC with bone metastases, with a safety similar to that of each treatment alone, versus enzalutamide alone (ENZ). Here we report the final OS analysis an updated safety data. Methods: EORTC1333/PEACE-3 is a randomized, open-label, multicentre phase III trial evaluating the addition of radium-223 (ENZ/RAD) to enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. In PEACE-3, a total of 446 asymptomatic or mildly symptomatic patients (Brief Pain Inventory <4) with mCRPC and ≥2 bone metastases were randomized 1:1 to Enza 160 mg daily alone or combined with six intravenous injections of Ra-223 (55 kBq/kg every 4 weeks). The study was conducted in collaboration with Clinical Trial Ireland (CTI), the Canadian Urological Oncology Group (CUOG), the Latin American Cooperative Oncology Group (LACOG), and the French group GETUG/UNICANCER. The primary endpoint was radiological progression-free survival (rPFS); overall survival (OS) and safety were key secondary endpoint. Results: At the final database lock (19 September 2025), 318 deaths were recorded (152/222 Enza+Ra-223; 166/224 Enza), representing 106.4% of the 299 expected events. Median OS was 38.2 months for Enza+Ra-223 and 32.6 months for Enza alone, corresponding to a hazard ratio (HR) of 0.75 (95% CI 0.60–0.95; one-sided stratified logrank p-value=0.0078, with a preset level of significance at final analysis of <0.0248.. Based on the permutation test, the statistical test on OS is significant (resulting in a 1-sided p-value of 0.0088 < 0.0248). The OS benefit was consistent across most predefined subgroups, except for age >75, for which the interaction was significant at the 10% 2-sided level. The previously published primary analysis (Ann Oncol 2025) demonstrated a significant improvement in rPFS (19.4 vs 16.4 months; HR 0.69; 95% CI 0.54–0.87; p=0.0009). The final analysis consolidates these findings, confirming prolonged OS and no new safety signals. Conclusions: The final results of EORTC1333/PEACE-3 confirm that adding six cycles of radium-223 to enzalutamide significantly prolongs overall survival in men with bone-dominant mCRPC, supporting the synergistic potential of this combination. Detailed analyses of efficacy, safety, and subgroups will be presented. Clinical trial information: NCT02194842 .

Clinical outcomes in patients with locally advanced or metastatic urothelial cancer (la/mUC) in France treated with avelumab first-line maintenance (1LM): A real-world observational study using the French National Healthcare Database (Système National des Données de Santé [SNDS]).

740 Background: Avelumab 1LM is a recommended treatment for patients with la/mUC without disease progression following 1L platinum-based chemotherapy. This study aimed to describe treatment patterns and outcomes in patients with la/mUC receiving avelumab 1LM treatment in routine clinical practice in France, using the SNDS database, which covers 99% of the national population. Methods: In this retrospective, noninterventional study, adults with unresectable la/mUC (ICD-10 codes: C65-C68.0, D09.0) with prior 1L chemotherapy (Z51.1) who received avelumab 1LM treatment between Jan 1 and Dec 31, 2021, were identified. Patients were followed up until death or end of follow-up (Dec 31, 2022), whichever occurred first. The overall primary study objective was to describe the clinical course of patients; secondary objectives included describing patient characteristics and overall survival (OS). Duration of treatment and OS were analyzed using the Kaplan-Meier method. OS was assessed in the overall population and subgroups with laUC or mUC. Results: In 1,090 patients with UC (any stage) who received avelumab 1LM following 1L chemotherapy, 892 (82%) were male, median age was 72 years (≥75 years in 321 [29%]), and 537 (49%) had metastatic disease. Patients received 1L chemotherapy for a median of 3.6 months (IQR, 2.5-4.4) before starting avelumab 1LM, and the treatment-free interval from end of chemotherapy to start of avelumab was < 4, 4-10, or > 10 weeks in 418 (38%), 583 (53%), and 89 (8%) patients, respectively. Median duration of avelumab 1LM treatment was 4.8 months (IQR, 2.1-10.3). At last follow-up, 658 patients (60%) were alive, 279 (26%) remained on avelumab, and 512 (47%) had received second-line treatment (63% of patients who discontinued avelumab). Median OS from the start of avelumab 1LM treatment was 22.1 months (95% CI, 19.6-26.5), and 1- and 2-year OS rates were 69% and 47%, respectively. No difference in OS was observed between subgroups with laUC (median, 22.2 months [95% CI, 18.8-not estimable]) or mUC (median, 20.7 months [95% CI, 18.1-26.5]). Additional effectiveness outcomes and subsequent treatment will be reported. Conclusions: This large observational study, using national data from France, supports findings from previous real-world studies showing the effectiveness of avelumab 1LM treatment in patients with la/mUC, irrespective of disease stage at treatment initiation. Results were generally consistent with an earlier study of avelumab 1LM treatment in France (AVENANCE; N = 595).

Impact of central venous pressure trajectories on prognosis in ICU patients with sepsis

[ ²²⁵ Ac]Ac-AKY-1189, a Nectin-4 targeted radiopharmaceutical, in patients with previously treated locally advanced or metastatic solid tumors: Phase 1b Nectinium-2 study.

TPS902 Background: Nectin-4 is a clinically validated target in metastatic urothelial cancer and is over-expressed in multiple additional solid tumor types suggesting a broad therapeutic potential. AKY-1189 is a high affinity and selective Nectin-4 targeted miniprotein which is rapidly cleared from plasma and shows a favorable normal tissue biodistribution in humans when conjugated to 68 Ga (Sathekge et al, 2024). [ 225 Ac]Ac-AKY-1189 is under development for the treatment of patients with locally advanced or metastatic solid tumors. [ 225 Ac]Ac-AKY1189 has been shown to induce regression and stasis in preclinical models of urothelial carcinoma after a single administration. Target-dependent efficacy of the radiopharmaceutical is observed at well-tolerated dosages. Available data support investigating the efficacy and safety of [ 225 Ac]Ac-AKY-1189 in a clinical study. Methods: The NECTINIUM-2 (NCT07020117) study is a first in human, phase 1b, 2-part (dose escalation and dose expansion), multi-center, open-label study of [ 225 Ac]Ac-AKY-1189. Key inclusion criteria are age ≥18 years; histologically or cytologically confirmed locally advanced or metastatic solid tumors; ≥1 measurable lesion per RECIST v1.1; ECOG of 0 or 1; adequate end-organ function; documented progression on prior lines of chemotherapy in the metastatic setting; and tumor uptake on a [ 64 Cu]Cu-AKY-1189 PET/CT scan. Key exclusion criteria are prior radiopharmaceutical therapy; investigational treatment in the past 4 weeks; and anticancer therapy or external beam radiotherapy in the past 3 weeks. The Part 1 dose escalation will investigate ascending doses of [ 225 Ac]Ac-AKY-1189 (up to 6 cycles) in ~30 patients with locally advanced or metastatic urothelial cancer. The aim of Part 1 is to determine the maximum tolerated dose (MTD) or maximum administrated dose (MAD) and the recommended Part 2 dose (RP2D) of [ 225 Ac]Ac-AKY-1189. Once RP2D is established, part 2 will evaluate the clinical activity of [ 225 Ac]Ac-AKY-1189 in 3 cohorts of patients with Nectin-4 positive solid tumors. NECTINIUM-2 has started enrolling subjects in the United States. Clinical trial information: NCT07020117 .

Topology‐Optimized Stretchable Piezoelectric Sensors With Tailored Liquid‐Metal Circuits for Anisotropic Stress‐Adaptive Motion Monitoring

ABSTRACT The design of high‐sensitivity stretchable piezoelectric sensors remains challenging due to the inherent trade‐off between the ability to achieve high levels of mechanical deformation while maintaining efficient stress transduction. Here, we propose a new topology‐optimization strategy to construct stretchable piezoelectric sensors that efficiently utilize the spatial stress distribution and are able to adapt to a range of anisotropic mechanical stress states. By exploiting computer‐aided topology optimization, the distribution of piezoelectric ceramic units within the sensor was tailored to maximize the degree of stress transfer, resulting in an increase of 103.5% and 59.7% in the maximum piezoelectric potential when subject to tension and torsion, respectively. To ensure structural stretchability and adaptability of the topology optimized sensors when subject to complex loading environments, a direct ink writing process was developed to create stretchable eutectic gallium‐indium liquid alloy (EGaIn) electrodes. Based on a shear‐driven mechanism of printing, new predictive theoretical equations governing printing performance were developed that could predict the printed state (with 94.7% accuracy) and enable trace width control (relative error < 15%). The final optimized sensor exhibited excellent sensitivity, achieving 14.0 V per strain and 0.10 V per degree when subject to tensile and torsional loads, exceeding the unoptimized device by 59.2% and 92.4%, respectively. Finally, inspired by the morphological characteristics of butterflies and guided by the topology‐optimized layout, a multi‐channel sensor was constructed to accurately identify the pattern and amplitude of a complex range of neck movements, demonstrating the significant potential of the new design and manufacturing approach for wearable electronics.

Cytomegalovirus-encoded immediate early 1 protein perturbs neural progenitor proliferation via interfering with host PML–DISC1 interaction

Incidence and co-occurrence of targetable key genomic alterations (GenAlt) in metastatic prostate cancer (mPC): Preliminary results from the prostate cancer cohort of the FPG500 program.

249 Background: PC is the most common male malignancy worldwide, associated with significant morbidity and mortality. GenAlt in some genes are critical drivers of tumor progression and dissemination. Emerging evidence are suggesting as some of these GenAlt can be used as predictive factors for response to therapies such as hormone therapy (SPOP), PARPi (BRCA and HRR), PTEN/AKT inhibitors (capivasertib) or highlight aggressive tumor phenotype (p53, Rb, TMPSRR-ERG), that deserve chemotherapy. In this study, we aim to describe the incidence and co-occurrence of key GenAlt in mPC. Methods: All tumor tissue samples of male patients affected by mPC, enrolled in the FPG500 program (NCT06020625), active at our institution, were included. Tumor tissue was analyzed using the TruSight Oncology 500 High Throughput (TSO500HT) assay. This analysis reported the incidence of pathogenic alterations in selected genes (BRCA1/2, ERG, p53, PTEN, Rb, SPOP, TMPSRR), as well as their co-occurrence. Results: Between January 2022 and May 2025, a total of 262 patients with mPC were enrolled in the FPG500 program and underwent comprehensive genomic profiling (CGP). In 115 cases (44%), sequencing was incomplete due to insufficient tumor material or DNA/RNA degradation. Among the 147 pts with complete CGP data, 128 (87%) harbored at least one genomic alteration. Clinically significant alterations (TIER I–II) were absent in 19 cases (13%). Baseline characteristics of the pts were: median age 73; mPC at the diagnosis in 80% of patients; high volume disease in 57% of cases; presence of bone metastases in 88% of cases. Among the evaluated population, 63% had at least one among the selected gene alterations. The incidence for each of these was BRCA1 in 1%, BRCA2 in 10%, ERG in 5%, p53 in 30%, PTEN in 18%, Rb1 in 1%, SPOP in 1% and TMPSRR in 20% of patients. The co-occurrence of GenAlt was found in 29% of patients and reported in the table below. Conclusions: Extensive genomic profiling can allow to identify targetable genes in over 60% of patients affected by mPC. This approach can facilitate access to personalized and potentially more effective treatment options. Future studies are warranted to elucidate the clinical implication of coexisting mutations in mPC. Clinical trial information: NCT06020625 . Frequency and co-occurrence of driven genetic alterations in treatment-naïve metastatic prostate cancer. Genetic Correlations (147 pts) BRCA 1(n°) BRCA 2 PTEN TP53 TMPRSS ERG SPOP Rb1 % (n°) 1% (2) 10% (15) 18% (26) 30% (44) 20% (29) 5% (7) 13% (19) 1% (2) BRCA 1 (n°) // 0 1 1 1 0 0 0 BRCA 2 0 // 2 4 1 0 1 0 PTEN 1 2 // 8 7 0 3 0 TP53 1 4 8 // 15 2 0 0 TMPRSS 1 1 7 15 // 4 0 0 ERG 0 0 0 5 4 // 0 0 SPOP 0 1 3 3 0 0 // 0 Rb1 0 0 0 0 0 0 0 //

Concurrent use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) in patients (pts) with advanced urothelial carcinoma (UC) receiving enfortumab vedotin (EV) plus pembrolizumab (P) therapy.

759 Background: Some advanced UC pts treated with EV plus P therapy have primary refractory disease or develop progressive loss of response to therapy, highlighting the need for synergistic approaches to augment treatment efficacy and duration of response. UCs that express higher levels of transforming growth factor-β (TGF-β) demonstrate poor responses to immunotherapy, while blockade of the renin-angiotensin system inhibits TGF-β. As such, we examined whether concurrent use of an ACEi or ARB during EV plus P therapy would correlate with improved clinical outcomes in pts with advanced UC. Methods: This is a retrospective analysis of advanced UC pts, who initiated EV plus P therapy at 6 academic institutions from 8/1/2018 to 9/1/2025. Pts needed to have at l east 1 whole body scan to assess for treatment response, which was interpreted using RECIST by the treating physician. Patients were divided into 3 subgroups: ACEi positive (cohort 1), ARB positive (cohort 2), or ACEi/ARB negative (cohort 3) at EV plus P start. Extracted data included demographic, clinical, treatment, and genomic variables. Primary study endpoint was median progression free survival (mPFS), defined as time from EV plus P initiation to progressive disease by RECIST version 1.1 criteria. Data was analyzed using descriptive statistics and Kaplan-Meier estimation. Results: A total of 253 pts were included, 73% were male, and median age was 72 years [range, 27 to 95]. Cohorts 1, 2, and 3 comprised 39, 58, and 156 pts respectively. Median pt age across the cohorts was similar, but the distribution of ages was skewed younger in cohort 3 (median 72, range 27-92) compared to cohorts 1 (72, 57-95) and 2 (75, 57-95) (Kruskal-Wallis, p = 0.011). Cohort 2 pts demonstrated a lower median glomerular filtration rate (GFR) (49, 10-97) compared to either cohort 1 (59, 16-96) or 3 (61, 10-122) (p = 0.055). There were otherwise no significant differences in characteristics among the cohorts. At a median follow-up of 11.1 months (mos), mPFS was 16, 18, and 12 mos in cohorts 1, 2 and 3, respectively (p = 0.6). Median overall survival (mOS) was 24, 21 and 33 mos in cohorts 1, 2, and 3, respectively (p = 0.7). Objective response rate (ORR) was 59%, 57%, and 57% in cohorts 1, 2, and 3, respectively. On multivariate analysis, age at EV plus P initiation, GFR, and ECOG variables correlated with inferior mPFS. Conclusions: Concurrent use of ACEi or ARB during EV plus P therapy did not affect outcomes in pts with advanced UC in this limited retrospective dataset. Analysis of tumor TGF-β expression and correlation with ACEi/ARB use could better elucidate the effect of these agents on responses to therapy in advanced UC. Prospective analysis could elucidate the effect of possible confounding factors such as ACEi/ARB dose and duration.