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Transcriptomic deep learning approach for predicting chemotherapy response to cisplatin and gemcitabine in urothelial carcinoma.

786 Background: Chemotherapy with cisplatin and gemcitabine remains the cornerstone of treatment for advanced urothelial carcinoma (UC), yet response rates vary significantly among patients. Predicting treatment response is crucial to avoid unnecessary toxicity and optimize therapeutic strategies. This study aims to develop a deep learning model leveraging RNA sequencing data to predict chemotherapy response in UC patients. Methods: We developed a deep learning model using RNA sequencing gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus to predict chemotherapy (Cisplatin and Gemcitabine) response in UC patients. The model was externally validated using an independent cohort from Pusan National University Yangsan Hospital. Model interpretation was performed through gene ontology and survival analyses using predictions from TCGA samples not included in the training set. Results: The deep learning model demonstrated excellent predictive performance, achieving 94.7% accuracy in the training dataset and 90.0% accuracy in external validation. Gene ontology analysis revealed four key functional clusters associated with chemotherapy response: DNA damage response, cell cycle regulation, kinesins/microtubule dynamics, and mitotic cytokinesis. Notably, the model showed significant prognostic value in early-stage (Stage I/II) patients, with predicted responders displaying markedly better survival outcomes (p = 0.019). Conclusions: Our transcriptome-based deep learning approach offers a promising computational strategy for predicting chemotherapy response in urothelial carcinoma. By integrating high-dimensional RNA-seq data and advanced machine learning techniques, this study provides a potential as decision-support tool for personalized treatment strategies.

Fostering inclusive language for genitourinary cancer research: A multi-stakeholder co-creation effort.

869 Background: Thoughtful patient inclusion, involving people of all literacy levels and experiences, is essential in cancer research and care. However, technical language can unintentionally exclude people from full participation. Plain language lexicons are structured sets of commonly understood terms and definitions that can help patients understand and consequently engage in scientific research. We co-created plain language lexicons to make genitourinary (GU) cancer research more accessible to patients. Methods: A four-step co-creation process was undertaken collaboratively with patients, advocates, and clinicians: 1) Identify the unmet need via a landscape search to gather available data, tools, and resources; 2) Develop and refine language through key stakeholder interviews and workshops; 3) Scrutinize the lexicons with key stakeholders; 4) Finalize the lexicons to be more inclusive of patient perspectives and improve accessibility of research data. The process was facilitated by Johnson & Johnson to enhance their patient engagement initiatives. Results: The bladder and prostate cancer lexicons included 62 and 84 prioritized terms, respectively, across categories such as diagnosis, treatment, and clinical trials. Examples of plain language terms used are shown in Table 1. Patients prioritized concise, jargon-free descriptions. Clinicians ensured plain language terms retained their intended scientific meaning. Post-rollout, the lexicons have supported researchers in using terms designed to align more closely with patients’ perspectives. The lexicons have been used by cross-functional teams on projects including advisory boards, surveys, and publications. The lexicons also serve as a reminder of the importance of using appropriate language to promote shared decision-making. Conclusions: Co-created plain language lexicons can broaden access to GU cancer research and help position patients as partners in evidence generation. Wider adoption and prospective evaluation, assessing comprehension, trust, and participation, are warranted. Sample terminology from the GU cancer plain language lexicons. Technical term Plain language term Rationale and use Anti-tumor effect Cancer-suppressing effect Avoid ‘war language’ like ‘fighting’ or ‘attacking’ which can be viewed as toxically positive Castration-resistant prostate cancer Prostate cancer that stops responding to hormone-lowering treatment Avoid using ‘castration’ in all cases Complete response No cancer after treatment Simpler language No evidence of disease No signs of cancer Avoid implying a cure or ‘cancer-free,’ which can create unrealistic expectations Radical cystectomy Bladder (and other sexual organ) removal surgery Provide explanation of the impact of radical cystectomy beyond the bladder, impacting quality of life

Clinical and genomic correlates of brain metastases in small cell carcinoma of the bladder.

807 Background: Small cell carcinoma of the bladder (SCCB) is a rare but aggressive subtype with a ~10% cumulative incidence of brain metastases (BM), markedly higher than in urothelial carcinoma (~1%). Patients with metastatic SCCB have a median overall survival (OS) of ~13 months, with expected worse prognosis after BM diagnosis. We aimed to identify clinical and genomic correlates of central nervous system (CNS) tropism in SCCB. Methods: We retrospectively analyzed 236 patients with metastatic SCCB treated at MD Anderson Cancer Center between 1992–2024. Patients who underwent brain MRI or contrast-enhanced CT were included and categorized as BM (n = 43) or no-BM (n = 99). Next-generation sequencing (NGS) was performed under CLIA-certified assays when available. Results: Among 142 evaluable patients, 43 (30.3%) developed BM; most were asymptomatic (67.4%) at diagnosis. Median survival after BM was 7.6 months (95% CI 4.7–9.1). Local CNS therapy was administered in 67.4% and systemic therapy in 55.8%. Within the metachronous metastatic cohort, BM occurred in 23 of 60 (38.3%) patients with ≤cT2 N0 disease and 11 of 23 (47.8%) with ≥cT3 or N+ disease. The odds ratio for higher versus lower stage was 1.47 (95% CI 0.56–3.89), indicating a statistically inconclusive association. Among patients who initially had localized disease, we did not observe higher odds of prior neoadjuvant chemotherapy among those who developed brain metastases compared with those who did not (OR 1.03, 95% CI 0.40–2.67, p = 0.95). On multivariable analysis adjusted for clinical stage, patients with pure small cell histology had greater odds of developing BM compared with those with mixed histology (OR 2.34, 95% CI 1.05–5.22, p = 0.038). Genomic data were available for 46 patients (16 BM; 30 no BM). Frequent alterations included TP53 (87%), TERT (46%), RB1 (41%), PIK3CA (24%), and ARID1A (20%). PIK3CA mutations were enriched among BM patients (43.8% vs 13.3%, OR 5.1, p = 0.03). Conclusions: Brain metastases were observed across a range of initial clinical stages among patients who later developed metastatic SCCB, supporting consideration of baseline MRI surveillance at diagnosis. PIK3CA alterations were enriched in BM, suggesting a potential biological role in CNS tropism. These findings justify translational studies of PI3K signaling and ongoing preclinical work testing brain-penetrant PI3K inhibitors in this disease. Variable, n (%) BM (n=43) No BM (n=99) p -value Sex, Male 30 (69.8%) 83 (83.8%) 0.071 Onset of metastasis Synchronous 9 (20.9%) 50 (50.5%) 0.001 Metachronous 34 (79.1%) 49 (49.5%) Histology Pure small cell 19 (44.2%) 30 (30.3%) 0.127 Mixed small cell (with UC) 24 (55.8%) 69 (69.7%) TNM at diagnosis T1N0M0 3 (7%) 5 (5.1%) 0.616 T2N0M0 20 (46.5%) 37 (37.4%) T3/4N0M0 7 (16.3%) 13 (13.1%) Any T, N+, M0 4 (9.3%) 13 (13.1%) Any T, Any N, M+ 9 (20.9%) 31 (31.3%) PCI History 4 (9.3%) 20 (20.2%) 0.145 Neoadjuvant Chemotherapy 25 (58.1%) 38 (31.3%) 0.91

Correction to “American Cancer Society’s report on the status of cancer disparities in the United States, 2025”

Multifunctional Fluidic Units for Emergent, Responsive Robotic Behaviors (Adv. Mater. 16/2026)

Toward a Consensus Characterization Protocol for Organic Thermoelectrics

ABSTRACT As the field of organic thermoelectrics advances toward maturity, an accurate and standardized reporting of performance metrics becomes essential to drive further progress and assess real‐world viability. The common geometric form factors and material properties (conductivity, anisotropy, stability, etc.) differ from those of conventional bulk inorganic systems, and thus specific recommendations may apply. Herein, we compile prevalent points of concern in the reporting of thermoelectric performance for organic materials and devices. Moreover, we propose a list of critical factors and metrics that should be explicitly documented when reporting the performance of novel organic thermoelectric materials or devices.

Chiral Acoustic Phonon and Conservation of Pseudoangular Momentum in α‐Quartz

Abstract While the linear motion of phonons is widely understood as arising from the translational symmetry of crystal lattices, recent studies have revealed the intrinsic rotational motion of phonons in condensed matter with discrete rotational symmetry. These phonons, termed chiral phonons, carry angular momentum associated with the rotational motion of atomic masses, as well as pseudoangular momentum arising from the phase winding of their circular motion. Chiral phonons give rise to novel physical phenomena such as Weyl phonons, valleytronics, and current‐induced spin selectivity. Furthermore, since acoustic phonons are the primary carriers of heat, chiral acoustic phonons are expected to play a significant role in spin caloritronics. However, the existence of chiral acoustic phonons has not yet been demonstrated, in contrast to the chiral optical phonons. In this study, the detection of chiral acoustic phonons is reported using Brillouin light scattering. It is found that the conservation of pseudoangular momentum, which governs the helicity‐dependent selection rules in photon–phonon interactions, manifests clearly for chiral acoustic phonons. By probing the previously uncharted low‐wavenumber, low‐frequency regime of chiral phonon dispersion, the findings expand the understanding of phonon chirality and its potential implications.

EXTRA-PC: A phase II trial of masofaniten (EPI-7386) and enzalutamide with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

148 Background: Masofaniten is a next-generation aniten which showed promising activity and safety in patients with metastatic castrate-resistant prostate cancer (mCRPC) (NCT05075577). Anitens are a family of oral N-terminal domain (NTD) inhibitors of the androgen receptor (AR). They may help overcome AR resistance mechanisms at the ligand-binding domain (LBD), which is the binding site of currently approved androgen receptor pathway inhibitors (ARPIs) such as enzalutamide, apalutamide, and darolutamide. The addition of an aniten to an ARPI and ADT may improve outcomes for patients with mHSPC over ARPI and ADT alone. Methods: In this investigator-initiated, phase II, single-institution trial, patients with treatment-naïve mHSPC were enrolled in a Simon 2-stage study design to receive the combination of masofaniten 600 mg BID and enzalutamide 160 mg daily with ADT. The primary endpoints included undetectable PSA (PSA <0.2 ng/mL) at 6 months, PSA progression-free survival (PFS), and radiographic PFS. The secondary endpoints were treatment-emergent adverse events and pharmacokinetics. The study was designed to enroll 35 patients (13 patients in stage 1, then 22 patients in stage 2). The trial would move to stage 2 if 9 or more subjects achieved an undetectable PSA at 6 months. Results: All 13 patients who were screened were enrolled into stage 1. Five were African American, and eight were Caucasian. Eleven patients had de novo metastatic disease. Median age was 68 years (range 52-75) at time of enrollment. Metastatic sites included lymph node (100%) and bone (85%). No patients had visceral metastases. Median PSA at time of enrollment was ng/mL (range 0.23-171.87), and 62% had a Gleason grade group 4-5. Median follow up time was 9.9 months (range 7.7-13.6). Ten of 13 patients (77%) achieved a PSA <0.2 ng/mL at 6 months, achieving the threshold to enroll to stage 2. Median time on masofaniten was 3.0 months (range 0.7-5.1). Two patients (16%) developed grade ≥3 adverse events (AEs) of neutropenia that were unrelated to the study drug. There were no serious treatment-related AEs. One patient had radiographic progression to mCRPC at 6.7 months and died of disease progression at 7.7 months. The remaining 12 patients are alive with no PSA or radiographic progression at the time of data cutoff. Based on the results of the mCRPC study (NCT05075577), further development of masofaniten was terminated by the sponsor. Thus, this study was closed prior to expansion to stage 2, and pharmacokinetics were not performed. Patients who were still on masofaniten discontinued the study drug and continued enzalutamide and ADT. Conclusions: The triplet combination of masofaniten, enzalutamide, and ADT for mHSPC did show efficacy and had an acceptable safety profile. Dual inhibition of the NTD and LBD of the AR is feasible in this setting. Clinical trial information: NCT06312670 .

KEYMAKER-U04 substudy 04B: First-line (1L) enfortumab vedotin (EV) plus pembrolizumab (pembro)-based immune checkpoint inhibitor (ICI) combinations for advanced urothelial cancer (UC).

634 Background: EV + pembro is the preferred standard 1L therapy for patients with locally advanced or metastatic UC (la/mUC). The randomized, open-label phase 1/2 substudy 04B in the KEYMAKER-U04 umbrella study (NCT05845814) aimed to build on the efficacy of this combination and evaluated EV + pembro–containing ICI coformulations and EV + pembro as 1L treatment in participants (pts) with la/mUC. Methods: Adult pts without prior systemic therapy for la/mUC and an ECOG PS of 0-1 were randomized 1:1:1 to EV + coformulated favezelimab (fave; anti–LAG3)/pembro 800 mg/200 mg (arm A), EV + coformulated vibostolimab (vibo; anti-TIGIT)/pembro 200 mg/200 mg (arm B), and EV + pembro 200 mg (arm C). Pts received EV 1.25 mg/kg IV on d1 and d8 Q3W until disease progression, intolerable toxicity, or study withdrawal, and pembro or pembro-containing coformulations IV on d1 Q3W for ≤2 years. A safety lead-in was performed for the first 10 pts in each of EV + fave/pembro and EV + vibo/pembro arms per modified toxicity probability interval with dose-limiting toxicity (DLT) monitoring in cycle 1. Primary end points: ORR per RECIST v1.1 by blinded independent central review (BICR) and safety. Secondary end points: PFS and DOR per RECIST v1.1 by BICR. Results: 124 pts received treatment (arm A: n = 41; arm B: n = 41; arm C: n = 42). Median follow-up (time from randomization to data cutoff [Dec 16, 2024]) (range) was 11.9 mo (9.7-17.0), 11.7 mo (9.7-16.3), and 11.8 mo (9.8-16.8), respectively. Most pts were male (74%); median age was 69 yrs. DLT was reported for 1/10 pts on EV + fave/pembro and no pts on EV + vibo/pembro. Efficacy results are in the table. Any-grade TRAEs were similar across all arms (arm A: 100%; arm B: 100%; arm C: 97.6%); grade ≥3 TRAEs were reported for 56.1%, 73.2%, and 61.9% of pts, respectively. Immune-mediated AEs and infusion reactions were reported for 65.9% pts in arm A, 53.7% in arm B, and 42.9% in arm C; immune-mediated AEs with > 10% higher incidence in any EV + pembro-containing ICI coformulation were hypothyroidism (31.7%, 14.6%, and 2.4%, respectively), severe skin reactions (24.4%, 29.3%, and 14.3%, respectively), hyperthyroidism (22.0%, 4.9%, and 4.8%, respectively), and infusion reactions (17.1%, 2.4%, and 0%, respectively). Conclusions: In pts with la/mUC, the addition of LAG3- or TIGIT-targeted ICIs to EV + pembro did not have a clinically significant impact on efficacy. No new safety signals were identified. Incidence of certain immune-mediated AEs was higher with pembro-containing coformulations compared to EV + pembro. Clinical trial information: NCT05845814 . Arm An = 41 Arm Bn = 41 Arm Cn = 42 ORR, % (95% CI) 66 (49-80) 59 (42-74) 57 (41-72) CR, n (%) 5 (12) 9 (22) 3 (7) DOR, median mo (range) NR (4.1 to 14.7+) 12.3 (2.5+ to 12.3) 12.1 (2.0+ to 12.1) PFS, median mo (95% CI) 11.3 (8.2-NR) 14.1 (5.1-NR) 10.9 (6.4-NR) 12-mo PFS rate, % (95% CI) 40.1 (15.1-64.3) 54.2 (37.4-68.3) 36.2 (18.9-53.9)

ProTACT: A first-in-human, phase 1 study evaluating the safety, tolerability, and anti-tumor activity of [ ²²⁵ Ac]Ac-FL-020, an anti-PSMA radioconjugate in patients with mCRPC.

164 Background: [ 225 Ac]Ac-FL-020 is a next-generation, prostate-specific membrane antigen (PSMA) alpha radioconjugate developed using the proprietary UniRDC linker-chelator technology designed to optimize biodistribution. [ 225 Ac]Ac-FL-020 is intended for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and aims to enhance tumor uptake while sparing radiosensitive organs, such as salivary glands, thus potentially leading to an improved therapeutic window. Methods: ProTACT (FL-020-001) is a first-in-human, open-label, multicenter Phase 1 study investigating the safety, tolerability, and preliminary anti-tumor activity of [ 225 Ac]Ac-FL-020 in patients with advanced PSMA-positive mCRPC. This Phase 1 clinical trial consists of 2 parts: a dose escalation phase (Part 1) and a dose expansion phase (Part 2). Patients eligible for enrollment must have: histologically confirmed mCRPC, evidence of disease progression, and ≥1 PSMA-positive lesion (uptake higher than liver) on PSMA positron-emission tomography/computed tomography imaging (PET/CT). Prior treatment with androgen receptor signaling inhibitors or CYP17 inhibitors and ≥1 taxane-based chemotherapy is required, unless declined by the patient. Prior therapy with Lu-177 is allowed. Patients with extensive PSMA-negative disease are excluded. Part 1 will apply a Bayesian logistic regression model (BLRM) with overdose control to guide dose-escalation decisions. Dose cohorts of 1 to 3 patients (for Cohorts 1 and 2) and dose cohorts of 3 to 6 patients (for Cohorts 3 and beyond) will evaluate ascending dose levels from 1 to 10 MBq (intravenous; every 6 weeks; x 6 cycles) to determine the maximum tolerated dose and/or recommended Phase 2 dose (RP2D). Once the RP2D is established, 18 additional patients will be enrolled in Part 2 to further assess safety and explore early signals of efficacy. Results: As of 23 September 2025, 7 eligible patients have received [ 225 Ac]Ac-FL-020 (maximum dose per cycle: 4 MBq). No xerostomia, unexpected safety signals, or dose-limiting toxicities have been observed. One subject in Cohort 3 experienced an unrelated Grade 3 adverse event (AE) of exacerbation of asthma due to metapneumovirus infection; and 1 subject in Cohort 1 died due to disease progression. All other reported AEs were Grades 1 to 2. Updated clinical data will be presented at the conference. Conclusions: These initial findings support the feasibility and tolerability of [ 225 Ac]Ac-FL-020 administration in heavily pretreated patients with mCRPC. The MTD has not yet been reached, and dose escalation continues. Further safety and efficacy data will be shared as enrollment progresses. Clinical trial information: NCT06492122 .

Targeting tumor suppressor gene co‐mutations in <i>EGFR</i> ‐mutant nonsmall cell lung cancer: How ACROSS2 sharpens the case for early intensification

Performance Constraints of All‐Perovskite Tandem Solar Cells in Low‐Intensity, Low‐Temperature Environments (Adv. Mater. 15/2026)

A Tongue‐Computer Tactile Interface Mediated by the Magnetoelectric‐Driven Tribovoltaic Sensors

ABSTRACT Current human‐computer interaction (HCI) technologies often suffer from wearing discomfort, noise sensitivity, user fatigue, and privacy concerns, particularly for users with physical disabilities or those requiring high‐precision control. In this study, we address the aforementioned challenges by designing an interactive tongue‐computer interface (ITCI) that enables precise, hands‐free interaction through subtle tongue movements. The ITCI utilizes an array of direct current tribovoltaic tactile sensors enhanced by the magnetoelectric effect, achieving a peak current density of 10.72 A m −2 , a charge density of 718 mC m −2 , and a sensitivity of 90 µA N −1 . integration with a bidirectional long short‐term memory (BiLSTM) neural network yields a recognition accuracy of 99.98%, supporting diverse interactive applications, including smart wheelchair control, robotic manipulation, and immersive gaming. This self‐powered, noninvasive interface enhances user autonomy and privacy, offering a robust platform for intelligent, energy‐efficient, and hands‐free human–machine interaction.

A phase 1b/2 study of FOR46 in combination with enzalutamide (enza) in patients with metastatic castration resistant prostate cancer (mCRPC).

149 Background: FOR46 is a monomethyl auristatin E antibody-drug conjugate targeting a tumor-specific epitope of CD46 that is highly expressed in mCRPC. In pre-clinical models, CD46 cell surface expression is upregulated following treatment with androgen receptor pathway inhibitors (ARPIs), enhancing tumor cell sensitivity to FOR46. We sought to determine the safety and efficacy of FOR46 in combination with enza in mCRPC patients (pts). Methods: Eligible mCRPC pts had progression on ≥ 1 ARPI and no prior chemotherapy for CRPC. The Phase (Ph) 1b dose escalation study to assess adverse events and select a recommended Ph 2 dose (RP2D) utilized a starting dose of FOR46 at 1.8 mg/kg adjusted body weight (ABW) q3 weeks in combination with enza 160 mg daily. The Ph 2 primary endpoint was composite response rate defined as PSA50 response or objective response by RECIST v1.1. Baseline CD46-targeted 89 Zr-DFO-YS5 PET imaging was mandatory in Ph 2 as an exploratory biomarker. Results: 44 pts were enrolled from 3/2022 to 7/2025. 6 pts remain on treatment as of 9/1/25. Median age at study entry was 72 (range 56-93), median baseline PSA was 31.2 ng/mL (range 0.8-1147.7 ng/mL), 61% of pts received ≥ 2 prior ARPIs, and 27% had visceral metastases. In Ph 1b, 17 evaluable pts were enrolled. The RP2D was established at FOR46 2.1 mg/kg ABW with G-CSF primary prophylaxis, in combination with enza 160 mg daily. In the overall study cohort (Ph 1b + 2), the median treatment duration was 3.5 mos (range 0.0-17.8 mos). The composite response rate was 21% (8/39 evaluable pts), with PSA50 response rate of 22% (8/37 evaluable pts) and objective response rate of 9% (1/11 evaluable pts). The median radiographic progression-free survival (rPFS) was 6.6 mos (95% CI 6.1-14.4 mos). Fewer lines of prior ARPI was associated with longer median rPFS [10.1 mos (1 prior ARPI) vs. 6.6 mos (2 prior ARPIs) vs. 5.1 mos (3 prior ARPIs), nominal p=0.048] and higher PSA50 response rate [40% (1 prior ARPI), 10.5% (2 prior ARPIs), 0% (3 prior ARPIs)]. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 8 pts (19.5%; n=2 for neutropenia, anemia, and hyponatremia). The most common any-grade TRAEs were fatigue (68%), peripheral neuropathy (56%), anorexia (41%), and dysgeusia (32%). 37% of pts discontinued treatment for TRAEs (17% for neuropathy; 11% for infusion reaction). 89 Zr-DFO-YS5 PET demonstrated tumor uptake in both bone and soft tissue lesions. Conclusions: FOR46 in combination with enza demonstrates anti-tumor activity in mCRPC pts, particularly for pts with one prior line of ARPI. The safety profile was consistent with the prior Ph 1 FOR46 monotherapy study. Cumulative toxicities, especially neuropathy, were dose-limiting for some pts. Predictive imaging and molecular biomarkers are under investigation. Clinical trial information: NCT05011188 .

Pilot phase I trial of an implantable microdevice for in vivo evaluation of drug response in renal cell carcinoma.

540 Background: Optimal treatment selection in renal cell carcinoma (RCC) remains challenging, but individual biomarkers based on tumor biology may enable personalized therapy and improve patient outcomes. We developed implantable microdevices (IMD) that can be placed into target tumors through a standard small-gauge interventional needle under imaging guidance. The IMDs deliver spatially segregated microdoses of up to 20 different locally administered drugs, including targeted, cytotoxic, and immunomodulatory agents, and/or combinations into the surrounding tumor tissue. Drug responses can be assessed within the tumor microenvironment without exposing the patient to systemic drug toxicity. Methods: Eligible patients had suspected or confirmed RCC planned for standard-of-care surgical resection of primary or metastatic tumors. Three (±1) days before surgery, one or more IMDs were percutaneously implanted into target lesions under CT guidance. At nephrectomy or metastasectomy, IMDs and adjacent tumor tissue were excised en bloc and fixed, embedded, and sectioned. Downstream analysis included H&amp;E stainings, immunohistochemistry (IHC) for apoptotic and VEGF pathway markers, cyclic immunofluorescence (cycIF) with a 25-marker panel for proliferation, apoptosis, and immune cell profiling, and spatial transcriptomics. Patients subsequently received standard systemic therapy at their oncologist’s discretion. Co-primary endpoints were safety (defined as ≤1 safety failures) and feasibility (defined as sufficient tissue for histopathological analysis of ≥50% of IMD wells). Results: Ten patients were enrolled including 7 clear cell and 3 non-clear cell RCCs. At time of IMD implantation, 50% had been pre-treated with checkpoint inhibitors and/or targeted therapy. A total of 33 IMDs were implanted into six primary tumors, three metastases, and one local recurrence in the nephrectomy bed. All IMDs were retrieved at surgery and 25 IMDs (75.8%) remained embedded in tissue after processing. Feasibility and safety endpoints were met with no safety events reported. IHC for cleaved caspase-3 showed drug-dependent patterns of apoptosis and spatial variation relative to the distance from the IMD. Differential immune cell compositions in the drug-exposed regions were identified by cycIF. Spatial transcriptomics delineated drug class effects on molecular pathways within the tissue microenvironment. Conclusions: In our pilot phase 1 study, percutaneous CT-guided implantation of IMDs in patient RCC tumors was safe and feasible and revealed differential drug effects on apoptosis, proliferation, and immune cell composition. Clinical trial information: NCT05700461 .

Multi-hit <i>PIK3CA</i> mutations in clinically advanced (CA) penile squamous cell carcinoma (penSCC): A genomic landscape study.

10 Background: Recent evidence confirms that tumors, such as advanced hormone receptor-positive breast cancer, can be highly responsive to PIK3CA inhibitors including alpelisib and inavolisib when ≥ 2 (“multi-hit”) PIK3CA mutations are identified by genomic analysis. We evaluated CA penSCC by comprehensive genomic profiling (CGP) to determine the frequency of multi-hit PIK3CA mutations in this aggressive and often chemotherapy-refractory cancer. Methods: Using the FoundationOne CDx assay, 365 CA penSCC underwent hybrid capture based CGP to identify all classes of genomic alterations (GA). Microsatellite instability status (MSI), tumor mutation burden (TMB), HRD signature, genomic ancestry, HPV status, and genomic signature were determined from the sequencing data. PD-L1 expression was determined by immunohistochemistry (IHC) using Dako TPS score (0% = negative; 1-49% = low positive; ≥50% = high positive). Results: 16 (4.4%) of CA penSCC featured ≥ 2 short variant PIK3CA mutations ( PIK3CA multi-hit+). The PIK3CA multi-hit+ group was slightly older (median age 70.5 vs 65.0; NS) and featured a slightly higher median number of GA per tumor (6.5 vs 5.0; p = .009). Genomic ancestry distribution revealed higher African ancestry in the PIK3CA multi-hit+ group and higher European ancestry in the PIK3CA multi-hit- group. Regarding putative biomarkers of anti-PD1/L1 response, median TMB was slightly higher in the PIK3CA multi-hit+ penSCC group, while PD-L1 expression ≥ 1% was relatively similar. MSI-high status was uncommon in both groups. HRD+ signature was more frequent in the PIK3CA multi-hit+ group. HPV positive status was more frequent in the PIK3CA multi-hit+ group. APOBEC genomic signature was also more frequent in the PIK3CA multi-hit+ group. Individual GA more frequent in the PIK3CA multi-hit+ penSCC (all NS) included ASXL, CCND1, ERBB2, FGFR3, KRAS , RB1. Individual GA more frequent in the PIK3CAmulti-hit- penSCC included CDKN2A, CDKN2B, EGFR, NOTCH1 which are all NS except TP53 (58.2% vs 12.5%; p = 0.012; Table). Conclusions: Multi-hit PIK3CA mutations are rare in clinically advanced penSCC but may offer opportunities for experimental therapeutic strategies, particularly in tumors with higher median TMB, HPV positivity, and co-alterations involving ERBB2 or FGFR3 . Study limitations include its retrospective design, lack of clinical / outcomes data annotation, potential selection and confounding biases. Further genomic investigation of penSCC is warranted to guide targeted drug development. PIK3CAmulti-hit+ PIK3CAmulti-hit- P-value n 16 349 MedianGA/tumor 6.5 5 0.009 Median TMB (mut/MB) 7.2 2.5 &lt;.0001 HRDsig positive (+) 6.7% 3.7% NS HPV 50.0% 28.9% NS APOBEC 31.3% 7.2% NS ERBB2 6.3% 1.1% NS FGFR3 12.5% 3.2% NS TP53 12.5% 58.2% 0.012

Nonpharmacologic interventions for managing distress, anxiety, and depression for patients with cancer and their family caregivers: A systematic review and meta‐analysis

Abstract As more cancer treatments take place in outpatient settings, family caregivers provide essential care and emotional support over long periods. Unaddressed patient and caregiver psychological distress can lead to worse outcomes, reflecting the challenges of managing complex care demands in the home setting. This systematic review and meta‐analysis examined how well nonpharmacologic interventions (NPIs) reduce distress, anxiety, and depression in adult patients with solid tumors and their family caregivers. The authors included 68 randomized controlled trials (RCTs) with a total of 11,987 participants. NPIs were characterized as psychoeducation, therapeutic counseling, skills training, or behavior modification. By using random‐effects models (Hedges g), they observed that NPIs significantly reduced patient distress at both 0.0–3.0 months (g = 0.13) and 3.1–6.0 months (g = 0.18), but NPIs did not significantly reduce caregiver distress. In the short term (0.0–3.0 months), NPIs also significantly reduced anxiety (g = 0.31 for patients; g = 0.15 for caregivers) and depression (g = 0.28 for patients; g = 0.25 for caregivers). Subgroup analyses examined the impact of patient and caregiver characteristics along with NPI type, delivery format, dose, and duration. NPIs delivered jointly to patients and caregivers yielded significant effects that were higher compared with NPIs delivered separately. NPIs can help manage distress in patients and reduce anxiety and depression in both patients and caregivers. However, the lack of long‐term follow‐up limits our understanding of their impact on patients and caregivers with prolonged or delayed psychological symptoms (PROSPERO registration number CRD42024536629).

Biofilm‐Antagonist Ginger‐Based 3D‐Printable Photoresins for Complex Implant Designs Exhibiting Advanced Multifunctional Biomedical Applications (Adv. Mater. 15/2026)

Evolution of Fe Single Atom in SiOC Ceramic Fibers and Their High‐Temperature and Ultrathin Electromagnetic Wave Absorption

ABSTRACT Accurately controlling the particle state and clarifying the relationship between particle structure and electromagnetic wave (EMW) are crucial for the development of high‐performance EMW absorbers, which are essential to address the challenges of electromagnetic pollution and stealth technology. However, achieving both high‐temperature resistance and low‐frequency response in ceramic‐based absorbers remains a significant challenge. Herein, we propose a metal nanoparticle diffusion‐dissolution mechanism through an atomic‐level engineering strategy to effectively control the evolution of Fe nanoparticles into Fe single atoms within SiOC ceramic fibers. By precisely optimizing the nitrogen source, the regulatory mechanisms of nitrogen doping on the evolution of iron species and the resulting electromagnetic behavior are systematically investigated. Due to the interaction between Fe single atoms (Fe‐N x ) and adjacent N/C atoms, the local microstructure symmetry of SiOC is disrupted, which improves the polarization behavior of SiOC─Fe─CN and enables multiple polarization loss mechanism. Notably, the SiOC─Fe─CN‐10 fiber exhibits exceptional absorption capability with a reflection loss (RL) of −59.33 dB at an ultrathin thickness of 1.60 mm and −58.0 dB at a low‐frequency of 5.93 GHz. The effective absorption bandwidth (EAB) reaches 5.5 GHz at a thickness of 1.49 mm. It also delivers remarkable high‐temperature (≥500°C) EMW absorption performance, with an RL of −53.2 dB at a low‐frequency of 4.78 GHz, which is the high performance of SiC‐based high‐temperature absorbers currently available. Moreover, the SiOC─Fe─CN‐10 composite demonstrates favorable thermal diffusion properties. This concept of precise control over particle state provides a valuable strategy for the design of high‐performance EMW absorbers and promotes the ongoing advancement of electromagnetic technology.

A phase 1/2, first-in-human study of AVZO-103, a bispecific Nectin4/Trop2 antibody-drug conjugate (ADC), as monotherapy and in combination therapy in patients with locally advanced or metastatic urothelial cancer (UC) or other solid tumors.

TPS908 Background: Nectin4 and TROP2 are transmembrane proteins frequently overexpressed in UC and other solid tumors, but with limited co-expression in normal tissue. Current single-target ADCs such as enfortumab vedotin (EV) have demonstrated clinical benefit, yet are limited by resistance mechanisms and safety concerns. AVZO-103 is a novel bispecific ADC designed to selectively target tumor cells expressing Nectin4 and TROP2. In preclinical xenograft studies including EV refractory models, AVZO-103 demonstrated robust tumor growth inhibition. By targeting both Nectin4 and TROP2, AVZO-103 potentially increases tumor cell coverage by addressing tumor heterogeneity of target expression while also delivering a potent topoisomerase I inhibitor, exatecan, to help overcome resistance to prior therapies. Methods: The Phase 1 part of AVZO-103-1001 study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of AVZO-103 as monotherapy (Part A) and in combination with an immunotherapy (Part B). Part A will enroll ~80 patients in a Q3W escalating schedule using a BOIN design to determine the maximum tolerated dose and preliminary recommended Phase 2 dose. Eligible patients are ≥18 years of age, ECOG PS ≤1, life expectancy of &gt; 3 months, ≤3 lines of cytotoxic chemotherapy in the metastatic setting (including non-topoisomerase inhibitor payload ADCs), with other prior therapies permitted including immunotherapy. Patients in Part A dose escalation have locally advanced or metastatic solid tumors known to express Nectin4 (UC, cervical cancer, triple-negative breast cancer, squamous cell carcinoma of the head and neck, non-squamous EGFR m NSCLC, and non-squamous NSCLC with no actionable genomic alterations) for whom standard therapies are no longer effective, appropriate, or declined by the patient. Backfill in Part A will enroll patients with locally advanced or metastatic UC. Part B will enroll ~35 patients, with doses to be guided by the outcomes of Part A. Primary objectives are safety/tolerability and secondary objectives include preliminary anti-tumor activity. Phase 2 will enroll ~240 patients. The trial is active and plans to enroll patients at centers across North America, Europe, and APAC. Clinical trial information: NCT07193511 .