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A randomized controlled trial evaluating anamorelin hydrochloride in patients with gastric cancer cachexia (TEAM-GUSTO).

e16037 Background: Cancer cachexia is a multifactorial metabolic syndrome associated with treatment interruption, deterioration in quality of life (QOL), and poor outcomes in patients with advanced cancer. Anamorelin, a ghrelin receptor agonist, has demonstrated efficacy in improving appetite, lean body mass (LBM), and body weight in lung cancer cachexia (ROMANA-1/2); however, randomized evidence in gastrointestinal cancers remains limited. We conducted a randomized controlled trial to evaluate the efficacy and safety of anamorelin in patients with gastric cancer cachexia. Methods: This multicenter, open-label randomized controlled trial was conducted across 10 institutions. Patients with unresectable or recurrent gastric cancer and cachexia receiving or planned for 1st–3rd line chemotherapy were randomized 1:1 to oral anamorelin hydrochloride 100 mg once daily for 12 weeks (Group A) or no anamorelin (Group N). Randomization was stratified by institution and gastrectomy status. The primary endpoint was change in lean body mass (LBM) at week 8. Secondary endpoints included total weight, quality of life (QOL), tumor response, chemotherapy compliance, and safety. Prespecified subgroup analyses included performance status, line of chemotherapy, and baseline plasma ghrelin categorized by the median value. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051210108). Results: Between October 2021 and July 2024, 203 patients were randomized; 198 were evaluable (Group A 101; Group N 97), with balanced baseline characteristics. At week 8, mean LBM change was +0.99 kg (95% CI 0.34–1.64) in Group A and +0.14 kg (–0.49–0.77) in Group N (P = 0.063). In a prespecified analysis of covariance adjusting for baseline LBM and type of gastrectomy, the adjusted mean difference in LBM change was +1.077 kg (95% CI 0.184–1.969; P = 0.018). Total weight increased in Group A (+1.17 kg; 95% CI 0.56–1.78) and decreased in Group N (–0.59 kg; –1.22–0.04) (P < 0.0001). Appetite-related QOL improved in Group A. No significant differences were observed in chemotherapy compliance or tumor response. Exploratory subgroup analyses suggested greater LBM benefit in patients with good performance status and those receiving first-line chemotherapy. Baseline ghrelin did not predict treatment effect. No severe treatment-related adverse events occurred. These findings indicate that anamorelin can be administered during chemotherapy without compromising treatment delivery, supporting its oncologic feasibility as a supportive intervention. Conclusions: In gastric cancer cachexia, anamorelin did not achieve a statistically significant increase in LBM at 8 weeks but significantly improved body weight and appetite-related QOL with a favorable safety profile. Anamorelin represents a feasible supportive option during chemotherapy in multimodal gastric cancer care. Clinical trial information: jRCTs051210108.

Patterns and timing of palliative care consultation in patients with newly diagnosed metastatic cancer.

12064 Background: Early integration of palliative care (PC) improves symptom burden, quality of life, and healthcare utilization in advanced cancer, yet referrals frequently occur late in the disease course. We evaluated institutional patterns of PC utilization to quantify consultation rates, timing, and demographic predictors of referral among patients with newly documented metastatic disease. Methods: We conducted a retrospective cohort study of adults with newly documented metastatic disease identified using ICD-10 secondary lymph node metastasis codes (C77.x) who received oncology care at the Mitchell Cancer Institute between November 2024 and November 2025. The first metastatic code defined time of diagnosis. Outcomes included PC consultation rate, time from diagnosis to consultation, consultation setting, and timing relative to death. Multivariable logistic regression evaluated associations between age, sex, insurance status, and race with receipt of consultation. Results: Among 375 patients (median age 66 years, IQR 56–74), 64 (17.1%) received a PC consultation. Consultation rates varied more than fourfold across primary diagnoses (6%–29%). Among patients with post-diagnosis consultations, the median time to consultation was 66 days (IQR 25–130), with more than half occurring >60 days after diagnosis. Most consultations occurred in the outpatient cancer center (78%). Among decedents who received consultation, 64% were first seen within 90 days of death, consistent with late referral. In multivariable analysis, increasing age was associated with a lower likelihood of consultation (OR 0.97 per year, 95% CI 0.95–0.99, p=0.016), while Black patients had higher odds of consultation compared with White patients (OR 1.82, 95% CI 1.02–3.25, p=0.044). Sex and insurance status were not independently associated with referral. Conclusions: PC utilization was low, highly variable, and frequently delayed among patients with metastatic cancer. Although most referrals originated in the outpatient setting, many occurred near the end of life. Diagnosis-triggered referral pathways may promote earlier and more equitable integration of supportive oncology services. Palliative care utilization and predictors of consultation. Characteristic Value Total patients 375 Median age, years (IQR) 66 (56–74) Received PC consultation 64 (17.1%) Median time diagnosis → consultation, days (IQR) 66 (25–130) Initial outpatient consultation 78% Consultation ≤90 days before death (decedents) 64% Black vs White race, adjusted OR 1.82 (p=0.044) Age (per year), adjusted OR 0.97 (p=0.016) Most referrals occurred late in the disease course >50% after 60 days PC = palliative care; IQR = interquartile range; OR = odds ratio. Timing calculated among post-diagnosis consultations. Odds ratios from multivariable logistic regression.

Surgical de-escalation in high-risk resectable melanoma with major pathologic response (MPR) after neoadjuvant immune checkpoint inhibition (ICI).

9574 Background: Neoadjuvant ICI renders MPR in 50-60% of resectable Stage III/IV melanoma. Early data illustrated the ability to de-escalate surgery in cases of MPR in the index lymph node (ILN). However complete lymph node dissection (CLND), a procedure with considerably morbidity, remains the standard of care. Real-world data demonstrating the ability to de-escalate surgery while maintaining disease control, can inform optimal practice. Methods: In our retrospective study performed at two academic institutions (MGB/DFCI), patients with resectable, macroscopic Stage III/IV cutaneous melanoma treated with neoadjuvant ICI were identified. Pre-treatment fiducial placement was routinely performed in cases of macroscopic nodal disease to facilitate index node excision (INE). Data pertaining to treatment course, anti-tumor outcomes, and safety were collected. Signatera ctDNA was evaluated as a non-invasive biomarker of early response. Results: From 2020-2025, 126 patients received neoadjuvant ICI: 60 anti-PD-1 monotherapy, 62 ipilimumab/nivolumab (I/N) and 4 nivolumab/relatlimab (N/R). The majority had macroscopic stage III disease (95%) and completed the full neoadjuvant course (86%). Ten patients (8%) did not undergo surgery (clinical CR, n = 3; toxicity, n = 1; progression, n = 6). Of the 116 (92%) who underwent surgery; 43 (37%) had an upfront TLND; 52 (45%) had an INE and 21 (18%) excision of N1c or M1a disease. After INE (n = 52), reflex CLND was performed in 7 (13%) all due to non-MPR. The MPR of the total cohort was 54% (n = 63) with a pCR rate of 51% (n = 59). The MPR/pCR rate was similar between ICI regimens. In the MPR cohort, 35 underwent an INE only whereas 17 underwent CLND; the remainder had excision of N1c/M1a disease. Post-operatively, 15 required drain placement, of whom 2 had an INE. Adjuvant ICI was utilized in 23 patients, the majority receiving peri-operative pembrolizumab (n = 20). After a median follow-up of 15.5mths (3.2-68.7mths), in those who underwent surgery, 20% (23/116) have recurred; 3 with a MPR (INE, n = 1; excision, n = 2). Of these, 2 were distant metastases with no nodal recurrence. Notably, 33 patients had pre-operative ctDNA results (Signatera). At the time of surgery, ctDNA was undetectable in the majority of MPR patients (19/20), while the majority of non-MPR patients remained detectable (8/13). Pre-surgery ctDNA assessment prognosticated RFS for the 20 patients who were detectable at baseline (p = 0.035) with ctDNA clearance associated with both MPR and improved RFS. Updated clinical and ctDNA data will be presented at the meeting. Conclusions: Similar to published data, patients with a MPR had low rates of recurrence, with no difference between those who underwent INE compared to upfront CLND. Pre-operative ctDNA levels, particularly ctDNA clearance, correlate with clinical outcomes and may inform de-escalation strategies.

BL0020, a novel tumor microenvironment (TME)-targeting nano-mediated polypeptide-drug conjugate (NMPDC), in patients with advanced solid tumors: Updated results from the small cell lung cancer (SCLC) subset of a phase 1 study.

8095 Background: BL0020 is a novel polypeptide-drug nanoconjugate (~10 nm in size) composed of PEG-modified poly(amino acid), enzyme-responsive peptide linkers, and topoisomerase I inhibitor (Topo1i) payloads. It accumulates in the tumor microenvironment (TME), where payloads are continuously released by specific enzymes, penetrate tumor cells, and effectively induce cell death. BL0020 has shown promising efficacy in advanced SCLC. Here, we present updated results from the SCLC subset of an international Phase 1 study of BL0020 (NCT05886868). Methods: Patients with locally advanced/unresectable or metastatic SCLC received BL0020 injection (20 mg/m² or 25 mg/m² IV every three weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Results: As of November 30, 2025, 49 patients were enrolled. Treatment-related adverse events (TRAEs) were consistent with expected payload-related effects, primarily manageable hematological and gastrointestinal toxicities, with no new safety signals identified. Grade 3/4 TRAEs occurring in ≥10% of patients included neutropenia, decreased white blood cell count, and anemia. All SCLC patients had progressed after at least one prior platinum-based chemotherapy regimen, and 61% had received prior anti-PD-(L)1 therapy. The median number of prior lines of therapy was 2 (range: 1–6). Among 13 efficacy-evaluable SCLC patients, the disease control rate (DCR) was 100% and the objective response rate (ORR) was 84.6%, with a confirmed ORR of 76.9%. In addition, eight patients achieved >50% tumor shrinkage. Among SCLC patients with baseline brain metastases, both ORR and DCR were 100%, with brain lesions showing >50% shrinkage or complete disappearance. At a median follow-up of 12.58 months, median progression-free survival (mPFS) was 10.15 months (95% CI: 4.93, not reached), median duration of response (mDOR) was 8.18 months (95% CI: 3.54, not reached), and median overall survival (mOS) was 15.31 months (95% CI: 7.46, not reached). Conclusions: BL0020 monotherapy demonstrated a manageable safety profile and promising antitumor activity in patients with advanced SCLC who progressed after at least one prior platinum-based chemotherapy. The therapy showed a high response rate and potential for prolonged PFS compared with standard chemotherapy. Clinical trial information: NCT05886868 .

Clinical factors driving use of RET inhibitor pralsetinib and associated real-world outcomes in <i>RET</i> fusion–positive NSCLC: A retrospective chart review.

e20731 Background: Selective RET (REarranged during Transfection) inhibitors (RETi) have become standard treatment for RET fusion-positive non-small cell lung cancer ( RET + NSCLC), which represent 1–2% of NSCLC cases. Clinical factors that drive front-line versus later-line RETi use and outcomes are not well understood. This retrospective chart review evaluates physician decision drivers alongside real-world effectiveness and safety for pralsetinib (PRAL) in RET + NSCLC. Methods: A retrospective chart review was conducted via a standardized web-based form among US oncologists treating advanced RET + NSCLC. Eligible patients initiated PRAL for RET + NSCLC between October 2020 and December 2024. Data gathered included physician treatment considerations, patient baseline characteristics, and efficacy outcomes. Results: Eighty-two charts from patients who received PRAL as their first (index) RETi were collected from 43 physicians across both academic (41.9%) and community (58.1%) sites. Of the 82 patients, 51.2% received PRAL front line (1L) and 31.7% in the second line (2L). From a predefined list, physicians most often cited comorbidities (36.6%) and ECOG performance status (31.7%) as clinical factors when considering index PRAL therapy and efficacy profile (56.1%), followed by intracranial activity (24.4%) and hypersensitivity to immuno-oncology agents (24.4%) as therapy-related considerations. Although not a primary therapy selection driver, in 13 patients with safety as a consideration, 6 (46.2%) had myelosuppression noted as a concern for index PRAL treatment. RET + NSCLC patients treated in the 1L setting with PRAL had an overall response rate (ORR) of 73.8% (14 CR; 17 PR). For 2L line PRAL, the ORR was 61.5% (1 CR; 15 PR). Anemia (17.1%), diarrhea (13.4%), and constipation (13.4%) were the most frequently reported adverse events (AE). Discontinuation was mainly due to loss of/no response (80.6%), insurance (16.1%), and AEs (3.2%). The single PRAL patient that discontinued due to an AE had edema. There were an additional 7 patients that switched to PRAL due to an AE on a different RETi. The post-switch ORR was 57.1% (4/7); of these patients, 3 maintained their previous response and 1 improved their response. Conclusions: In this retrospective chart review, pralsetinib was used across treatment lines with high real-world response rates, consistent with results from the ARROW trial. Treatment selection was influenced by specific clinical factors including patient comorbidities, ECOG performance status, and safety concerns, with AE-driven switching uncommon yet associated with continued responses.

Real-world outcomes and immune and cardiopulmonary toxicities of durvalumab following concurrent chemoradiotherapy in non–small cell lung cancer.

e20097 Background: Durvalumab consolidation following concurrent chemoradiotherapy (CCRT) has improved overall survival (OS) in locally advanced non–small cell lung cancer (NSCLC). Long-term real-world effects of consolidation of immunotherapy on outcomes, including aggregate risk of immune and cardiopulmonary events, remain unclear. Methods: We performed a retrospective analysis using the SEER-Medicare database (2013–2020). We employed propensity score matching for the cohort of NSCLC patients who had received durvalumab, where each patient was paired with a non-durvalumab receiving patient to ensure balance across selected covariates, including age, sex, race, stage, and Charlson comorbidity index (CCI). Immune-related adverse events (irAEs), and cardiopulmonary events were identified using claims-based definitions. Cox proportional hazards and Fine–Gray competing-risk models were applied. Results: In total, 3554 patients with NSCLC who received durvalumab were identified. After propensity matching, 2751 patients were included in each cohort. Durvalumab was associated with significantly prolonged median OS duration compared with no durvalumab (44.6 vs 25.0 months, P&lt; 0.001), closely approximating survival outcomes reported in the PACIFIC trial (47.5 vs. 29.1 months).Durvalumab was associated with increased risks of irAEs, including pneumonitis (sHR 1.84, P&lt; 0.001), hypothyroidism (sHR 1.82, P&lt; 0.001, Hashimoto’s thyroiditis (sHR 2.68, P&lt; 0.001), autoimmune hepatitis (sHR 3.62, P= 0.03), dermatitis (sHR 1.80, P= 0.02), and gastroenteritis/colitis (sHR 1.31, P&lt; 0.001). The cumulative incidence of pneumonitis and hypothyroidism approached approximately 20% and 35% at three years, respectively, with pneumonitis occurring predominantly within 18 months, while increased risk of hypothyroidism continued to occur beyond two years. In contrast, durvalumab was associated with lower risks of cardiomyopathy (sHR 0.74, P= 0.003), heart failure (sHR 0.87, P= 0.005), acute respiratory failure (sHR 0.29, P&lt; 0.001), and COPD exacerbation (sHR 0.78, P&lt; 0.001). Racial differences in select irAEs were observed and warrant further investigation. Conclusions: In this large real-world analysis, durvalumab consolidation following CCRT was associated with substantial OS benefit in patients who received CCRT. While irAEs were increased, non-immune related cardiopulmonary outcomes were unexpectedly more favorable. The timing and burden of toxicities highlight the importance of early monitoring for pneumonitis and prolonged surveillance for endocrine irAEs.

Subtype-specific melatonin receptor expression on circulating tumor cells and associated inflammatory/metabolic biomarkers in breast cancer: A 3-year cohort analysis (n=171).

e13016 Background: Melatonin signaling modulates inflammation, extracellular matrix remodeling, and tumor metabolism. We investigated whether melatonin receptor expression on circulating tumor cells (CTCs) differs by breast cancer subtype and whether it aligns with systemic biomarkers reflecting inflammation and metabolic reprogramming. Methods: Over three years, 171 breast cancer patients were grouped as triple-negative breast cancer (TNBC), HER2/neu-positive and ER/PR-negative, Luminal A, or Luminal B. Blood and urine were collected for plasma melatonin, urinary melatonin sulfate, matrix metalloproteinases (MMPs), IL-6, TNF-α, and LDH isoenzymes (LDH-1, LDH-5). CTCs were isolated using density gradient centrifugation and immunomagnetic separation; melatonin receptor expression on CTCs was evaluated by flow cytometry and immunocytochemistry. Melatonin was quantified by HPLC; MMPs/cytokines by ELISA; LDH isoenzymes by electrophoretic methods; urinary melatonin sulfate by RIA. Between-group comparisons used one-way ANOVA; correlations used Pearson testing (p &lt; 0.05). Results: Melatonin receptor expression on CTCs was lowest in TNBC, higher in HER2/neu-positive ER/PR-negative, and highest in Luminal subtypes (maximal in Luminal A). TNBC demonstrated an aggressive systemic profile: LDH-1 elevation in 75% (LDH-5 not elevated), IL-6 elevation in 90%, TNF-α in 98%, and significantly decreased melatonin. HER2/neu-positive ER/PR-negative disease showed LDH-5 elevation in 59% with moderate melatonin decrease (IL-6 81%, TNF-α 93%). Luminal B showed LDH-5 elevation in 47% with moderate melatonin decrease (IL-6 72%, TNF-α 95%). Luminal A showed LDH-5 elevation in 35.5% with mild melatonin decrease (IL-6 51%, TNF-α 98.3%). Across subtypes, lower CTC melatonin receptor expression tracked with higher inflammatory cytokines and subtype-specific LDH patterns. Conclusions: Reduced melatonin signaling (lower CTC melatonin receptor expression and lower melatonin) is associated with more aggressive breast cancer biology, particularly TNBC, and aligns with inflammatory activation and distinct metabolic isoenzyme shifts. A combined panel integrating CTC melatonin receptor expression with melatonin/MMPs/cytokines/LDH isoenzymes may support biologic stratification and inform melatonin-based interventional trial hypotheses.

Eating disorder-related electrolyte abnormalities and adverse outcomes: A systematic review and meta-analysis

Objective The aim of this study is to describe the association between electrolyte abnormalities and adverse clinical outcomes, as well as to estimate the prevalence of these abnormalities in individuals with eating disorders. Design Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020-compliant systematic review searching Ovid MEDLINE, EMBASE, and PsycINFO databases from January 2000 to February 2025 was conducted. Methods We included studies with any electrolyte abnormality or clinical adverse outcome among individuals with eating disorders. We conducted two meta-analyses to assess (1) the odds of having an electrolyte abnormality among those with an eating disorder diagnosis compared to healthy controls, and (2) the prevalence of electrolyte abnormalities across eating disorder diagnoses. Results 20 studies incorporating 25,401 individuals were analysed, with most assessing a young female population. Study designs were predominantly retrospective cohort (n = 11) and cross-sectional (n = 5), with few including general population controls (n = 4). Anorexia nervosa was the most common eating disorder studied, with hypokalemia (n = 13 studies), hyponatremia (n = 11 studies), and hypophosphatemia (n = 7 studies) being the most frequently reported electrolyte abnormalities. The most prevalent adverse outcomes included anemia (n = 5 studies) and skeletal conditions (osteoporosis, osteopenia; n = 5 studies). The results from the meta-analyses showed (1) that individuals with eating disorders had significantly higher odds of experiencing electrolyte abnormalities compared to controls (OR = 3.20, 95% CI:1.48–6.94), and (2) varying pooled prevalences of abnormalities, including hypokalemia (15%), hyponatremia (13%), and hypophosphatemia (17%), across studies. Conclusion Electrolyte abnormalities are common among individuals with eating disorders and are associated with adverse health outcomes. Trial Registration The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) – (ID CRD42023477497)

Fast design and fabrication of patient-specific metasurfaces toward intraocular lens applications

Multifocal intraocular lenses (IOLs) provide functional vision at multiple distances, yet clinical satisfaction is strongly influenced by patient-specific through-focus preferences among near, intermediate, and far vision, which are rarely encoded as a first-class design variable in conventional diffractive optics. Here, we report a preliminary design-to-fabrication investigation of patient-specific flat metasurface prototypes for prospective IOL applications. A scalar wave-optics model maps a low-dimensional focus preference profile into a two-dimensional phase distribution on a 500 nm lattice over a 3 mm pupil using an area-fraction tri-focal construction. Four representative cataract-patient preference profiles are investigated: near-dominant, intermediate-dominant, far-dominant, and balanced. The continuous phase profile is discretized into a polarization-insensitive nanopillar library, enabling UV nanoimprint-based replication using a reusable soft mold and a high-index TiO2-polymer composite. Benchtop point spread function measurements of the fabricated flat metasurface prototypes reproduce the predicted preference-dependent redistribution of optical energy across near, intermediate, and far focal planes. These results establish the optical and manufacturing feasibility of fast, preference-tailored flat metasurfaces as a preliminary step toward future IOL applications. However, the present work addresses planar two-dimensional metasurface patterns rather than curved three-dimensional implantable lenses. Further studies are required to integrate such metasurfaces with realistic IOL geometries, evaluate performance in eye models and clinically relevant visual tasks such as reading, computer work, and driving, and assess biocompatibility, sterilization, long-term stability, and surgical handling.

Bone tissue engineering and drug-eluting implants for enhanced bone regeneration: An update

Perspective on Material Design and Interface Engineering toward Low‐Stack‐Pressure All‐Solid‐State Lithium Batteries

ABSTRACT All‐solid‐state lithium batteries (ASSLBs) have garnered worldwide attention as promising next‐generation energy storage technologies owing to their high energy densities and enhanced safety. However, their long cyclability remains unsatisfactory for practical application, primarily due to poor solid‐solid interfacial contact. A high stack pressure is often required during operation, hampering their commercialization. This perspective presents a fundamental understanding of the roles of stack pressure in ASSLBs and analyzes the intrinsic challenges to achieve optimal battery performance under low‐stack‐pressure conditions. Recent advances for reducing high‐stack‐pressure demands are summarized from the point of views of solid electrolyte/ active electrode material design and interface engineering. Finally, the perspective layouts the key challenges and prospects for future breakthroughs to achieve low‐stack‐pressure ASSLBs. It is hoped that the material‐centered solutions highlighted in this perspective will inspire meaningful progress in future advanced battery systems.

4D‐Printed Spin Crossover Metamaterials with Giant Programmable Positive or Negative Thermal Expansion

ABSTRACT In the past decade, 3D‐printed cellular materials have witnessed an impressive advancement affording a wealth of remarkable mechanical properties, such as negative Poisson's ratio, negative compressibility, and negative coefficient of thermal expansion (CTE). Recent efforts in this field have been increasingly considered 4D‐printed metastructures, which leverage shape‐morphing properties of stimuli‐responsive materials. Here, we introduce a new class of 4D‐printed metamaterials based on bistable spin crossover (SCO) molecular materials. These systems synergistically couple dissimilar materials at different size scales to harness mismatched thermomechanical properties—specifically differential thermal expansion and stiffness—to generate large directional deformations upon heating or cooling. Through a combination of theoretical modeling and experimental validation, we demonstrate that our SCO‐based 4D‐printed structures can achieve programmable motions, including positive and negative expansion. The associated CTE reaches peak values of ca. +14400 and −11400 ppm/°C, respectively, more than 10 times greater than those reported in the literature for 3D‐printed analogues. This work establishes a versatile and generalizable conceptual strategy for engineering multilevel, hierarchical architectures with programmable functionalities, advancing the design of energy‐efficient soft actuators and reconfigurable/adaptive material systems.

Experimental investigation of mechanical and optimization of machining parameters of nanoclay-filled glass reinforced plastic composite

Abstract In this study, an experiment has been conducted on the mechanical properties and machinability of nanoclay-filled glass fiber reinforced plastic composites. GFRP composites with 0, 1, 3, and 5 wt% nanoclay contents have been prepared and tested for density, tensile, and flexural properties based on ASTM procedures. Results show improved tensile and flexural strengths and moduli upon adding nanoclay, with the best results at 3 wt% nanoclay. The machinability experiments were carried out using CNC milling, and the influence of nanoclay reinforcement, spindle speed, feed rate, and cutting depth on the surface roughness (Ra) and material removal rate (MRR) was investigated using response surface methodology based on Box–Behnken design. The results of ANOVA confirmed that the proposed models were statistically significant. The nanoclay reinforcement, spindle speed, feed rate, and cutting depth were found to have a major influence on surface roughness and MRR, respectively. The multi-response optimization procedure revealed that the optimal machined layer at moderate nanoclay and spindle speed could minimize the surface roughness while maximizing the productivity. This paper offers conclusive evidence that the controlled nanoclay reinforcement improves the mechanical and machinability properties of GFRP composite materials.

Light‐Induced Entropy for Secure Vision

ABSTRACT We present a photospike‐based true random number generator (PS‐TRNG) that exploits the intrinsic randomness from light–matter interaction and stochastic charge trapping. By integrating copper vanadate (CuV 2 O 6 ) nanostructures with a tin dioxide quantum dot (SnO 2 QD) layer, the device induces probabilistic trapping–de‐trapping dynamics, producing random photospike currents under optical pulse trains. The spike currents show high entropy and enable multi‐level random number generation beyond binary, providing ternary outputs with near‐ideal statistics (33.30% uniformity, 33.28% inter‐Hamming distance) and full success in all 15 NIST tests. We further develop an image authenticity verification system by integrating the PS‐TRNG with a mobile platform and custom‐designed circuit board, enabling hardware‐based detection of unauthorized image modifications. The random numbers are embedded as a hidden layer within the image data without degrading visual quality, enabling detection of unauthorized modifications. The system can successfully identify image modifications, even those involving highly sophisticated manipulations generated by artificial intelligence (AI)‐based image editing tools. The device maintains stable operation over 2 million cycles and remains reliable even after more than 460 days, demonstrating its long‐term stability.

Structure and enzymology of glutaminase S482C and H461L variants associated with excess brain glutamate and neurological disease

Real-world costs of care and discontinuation among patients receiving adjuvant CDK4/6 inhibitors in early breast cancer.

e12517 Background: For patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) early breast cancer (eBC) at high risk of recurrence, CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are approved in the adjuvant setting. However, real-world data on treatment discontinuation and costs of care remain limited. Our study quantifies these outcomes in patients receiving adjuvant CDK4/6i in a real-world setting. Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2− eBC who initiated abemaciclib or ribociclib in combination with ET in the adjuvant setting from 01/01/21–03/31/25 (initiation date = index date) using the IQVIA PharMetrics Plus database. Patients were required to have 12 months pre-index continuous enrollment (CE) and were followed from index until the earliest of end of CE, 12 months post CDK4/6i initiation, metastatic diagnosis code, or initiation of other therapy (metastatic treatment or PARP inhibitor). Discontinuation was defined as a gap of &gt;60 days in CDK4/6i days’ supply based on pharmacy claims or a switch to PARP inhibitor. Costs of care (including outpatient costs, inpatient costs, emergency department costs, and pharmacy costs) were evaluated during the follow-up period for each patient. Costs were computed at a per patient per month (PPPM) level and then annualized. Results: A total of 1,338 patients were included. During the 12-month baseline period prior to CDK4/6i plus endocrine therapy (ET) initiation, mean total healthcare costs were $125,689.79. The mean time from breast cancer surgery to CDK4/6i initiation was 7.19 months. Based on Kaplan-Meier estimates, 31% of patients discontinued CDK4/6 inhibitor therapy within one year of initiation. The mean annualized per-patient-per-month (PPPM) total costs during follow-up were $209,524, driven primarily by pharmacy costs ($166,842), followed by outpatient costs ($32,527) (Table 1). Conclusions: This study provides current real-world costs of care and discontinuation estimates for patients who receive CDK4/6i in the adjuvant eBC setting. CDK4/6i discontinuation rates at 1 year were higher than those reported in clinical trials, which generally report lower discontinuation rates over longer follow-up, and were consistent with prior real-world evidence. Total PPPM costs are driven primarily by pharmacy and outpatient expenditures. PPPM annualized healthcare costs. Variable Mean (SD) Total Annualized Cost $209,524 (147,588) Inpatient (IP) Cost $9,674 (107,007) Emergency Room (ER) Cost $482 (1,607) Outpatient (OP) Cost $32,527 (46,682) Pharmacy (Rx) Cost $166,842 (94,434)

The significance of MDM-2 positivity in stage 4 non-small cell lung cancer.

e20599 Background: MDM-2 positivity is discussed as a potential indicator of resistance to immunotherapy and targeted therapies in many cancer types. Our study will investigate the effect of MDM-2 levels on treatment response and overall survival in patients with unresectable/metastatic NSCLC, the majority of whom received second-line or later immunotherapy(IO). Methods: 81 patients followed at our center were included in the study. Immunohistochemical evaluation of MDM-2 levels was performed on the pathology slides of our patients. The distribution of best response after IO was recorded as follows: CR 11 (16.2%), PR 41 (60.3%), PD 11 (16.2%), and mixed response 5 (7.4%). Statistically significant differences were found in the following variables: bone metastasis, liver metastasis, duration of IO, best response after IO, hemoglobin level, and progression status. Bone metastasis (p = 0.001) and liver metastasis ( p = 0.037) were more frequent in patients who died. The duration of IO was longer in the surviving group, with a median of 16.5 months (IQR: 6.0–31.5), compared to a median of 3.0 months (IQR: 2.5–8.5) in the death group (p &lt; 0.001). Hb levels were higher in the surviving group (median 12.80) and lower in the death group (median 11.5) (p = 0.003). The distribution of best response after IO differed significantly between the two groups (p &lt; 0.001); the complete response rate was higher in the surviving group (Survivors: 32.3%; Deaths: 2.7%). Results: The survival difference between the two groups, categorized as MDM-2 levels ≤2 and &gt; 2, was statistically significant. Median survival was 26.3 months in the MDM-2 ≤2 group and 6.6 months in the MDM-2 &gt; 2 group . In the MDM-2 ≤2 group, survival rates were found to be 69.9% (SE = 6.1) at 1 year, 46.0% at 3 years, 28.6% (SE = 8.6) at 5 years, and 14.3% at 10 years; in the MDM-2 &gt; 2 group, the survival rate was determined to be 52.9% (SE = 11.4) at 1 year and 16.5% at 3 years.(p = 0,033). Conclusions: We believe that our study will make a significant contribution to the literature as it is the first real-life study investigating IO resistance in unresectable/metastatic NSCLC, showing a significant association between MDM-2 levels and survival. MDM-2 % &lt;2 &gt;2 Survival Rate % SE % SE 1 year 69,9 6,1 52,9 11,4 3 years 46,0 6,9 16,5 10,1 5 years 28,6 8,6 10 years 14,3 11,0

Prophylactic tocilizumab to mitigate cytokine release syndrome in patients receiving tarlatamab: A single-center exploratory experience informed by bispecific antibody safety data.

8082 Background: Tarlatamab, a bispecific T-cell engager (BiTE) targeting CD3 on T cells and DLL3 on small cell lung cancer (SCLC) cells, represents a major advance in treating relapsed or refractory SCLC. By activating T cells to release cytotoxic cytokines, it induces tumor cell death but carries risks such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). In the phase 2 DeLLphi-301 trial, CRS occurred in up to 53% of patients treated with Tarlatamab. Current inpatient step-up dosing protocols aim to mitigate toxicity but add cost and complexity, particularly for immunocompromised patients. Tocilizumab, an interleukin-6 (IL-6) receptor inhibitor used for CRS, has demonstrated prophylactic benefit in mitigating cytokine-related adverse events with other BiTEs such as teclistamab. We hypothesized that prophylactic tocilizumab could similarly reduce Tarlatamab-related CRS in SCLC without compromising efficacy. Methods: We retrospectively analyzed 32 consecutive SCLC patients treated with Tarlatamab at our center. Tocilizumab (8 mg/kg) was administered 1 hour prior to the first Tarlatamab dose when approved by insurance. CRS incidence, grade, rescue interventions, treatment discontinuations, and cost implications were evaluated. CRS grading followed standard consensus guidelines. Results: Among 32 treated patients, 29 (90.6%) received prophylactic tocilizumab, and 3 did not. CRS developed in 3 of 29 patients (10.3%) who received pre-treatment—two grade 1 and one grade 2. In contrast, all 3 patients (100%) who did not receive pre-treatment developed CRS—two grade 1 and one grade 2. Overall, CRS occurred in 6 patients (18.8%). All cases resolved after tocilizumab rescue therapy, and no treatment discontinuations occurred. Conclusions: Prophylactic tocilizumab substantially reduced CRS incidence among SCLC patients receiving Tarlatamab, suggesting a feasible and safe mitigation strategy. Compared with historical data from DeLLphi-301 (53% CRS incidence), this cohort exhibited markedly lower toxicity rates with prophylactic IL-6 blockade. To our knowledge, this represents the first clinical evidence supporting IL-6 blockade before Tarlatamab administration. Despite the upfront drug cost ($2,800–$5,100 per dose), prevention of CRS-related hospitalizations offers significant economic benefit (estimated $11,000–$200,000 per event based on grade). Limitations include small sample size, lack of randomization, and single-center design. Nonetheless, these findings underscore the potential of integrating tocilizumab prophylaxis into standard Tarlatamab protocols and warrant larger prospective studies to confirm safety, efficacy, and cost-effectiveness.

Cerebrospinal fluid cell-free tumor DNA-based cancer molecular profiling vs. cytology examination: A comparison in cancer detection sensitivity.

e15057 Background: The evaluation tools with the central nervous system (CNS) tumors includes magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology, and brain biopsies all of which have certain limitations. Those assessments also lack the function of treatment guidance and minimal residual disease surveillance. On the hand, the innovation of mutation detection from cell-free DNA (cfDNA), specifically circulating tumor DNA (ctDNA), further provides incredible advantage in cancer diagnosis, treatment selection and disease progression surveillance. Hereby, we want to compare the sensitivity and specificity of tumor detection between cfDNA and cytology. Methods: We compared the tumor detection between CSF ctDNA-based mutation profiling and conventional CSF cytological examination in 106 cases which had both results. Results: In total 106 CSF samples from patients with clinically suspicion of leptomeningeal metastases (LM) and/or intraparenchymal metastasis, cfDNA-based testing detected previously known variants in 60 samples (56.6%), while cytological examination only picked up 28 positive cases (26.4%). Specifically, 1) 24 cases were positive by both ctDNA and cytology, 2) 36 cases were positive only by cfDNA and 3) 4 cases were positive only by cytology. Conclusions: Taken together, our results indicate a significant value of simultaneously performing ctDNA-based comprehensive cancer profiling on CSF samples to managing patients with brain tumors, especially in patients with metastatic CNS carcinomas.

Updated overall survival analysis and examination of subsequent therapy in endometrial cancer (EC) patients (pts) treated with pembrolizumab plus carboplatin/paclitaxel (CP) as compared to CP plus placebo (PBO) in the NRG-GY018 trial.

5502 Background: NRG-GY018, the only phase 3 trial examining dMMR and pMMR EC populations independently, identified a 70% and 46% reduction in the risk of disease progression or death in advanced stage or recurrent dMMR and pMMR EC patients treated with pembrolizumab plus CP. Here we report on updated overall survival and post-study immune checkpoint inhibition (ICI) therapy. Methods: 810 pts were randomized 1:1 to pembrolizumab + CP or PBO + CP Q3W for 6 cycles followed by maintenance pembrolizumab or PBO Q6W for up to 24 months. Updated OS analysis data cut off was December 23, 2025, with information fraction of 42% and 78% in the dMMR and pMMR EC cohorts, respectively. Median follow up in the dMMR cohort was 44.6 months (95% CI 42.5 to 46.8) and 40.1 months (95% CI 38.9 to 42.2) in the pMMR cohorts. Study sites were queried to abstract data regarding start and end date of post study ICI use. Results: The addition of pembrolizumab resulted in a sustained OS benefit in the dMMR EC cohort. At 48-month landmark assessment, 80% of the pembrolizumab treated dMMR EC patients were alive, versus 60% of those treated with placebo, HR 0.53 (95% CI 0.32 to 0.89). This survival advantage was maintained despite at least 55% (n=62) of dMMR EC patients in the placebo arm receiving post study ICI. In the pMMR EC population, with an information fraction of 78%, the median OS in the pMMR cohort treated with pembrolizumab was 46.9 months versus 35.1 months for those receiving placebo, HR 0.84 (95% CI 0.66 to 1.06). This benefit was maintained despite at least 57% (n=167) pMMR EC patients in the placebo arm receiving post study ICI (most commonly lenvatinib plus pembrolizumab). In the pMMR EC cohort, 70 patients in the pembrolizumab arm and 167 patients in the placebo arm received post study ICI, with the median duration of treatment of 6.2 months in both populations. Conclusions: In the NRG GY018 study, with prolonged follow up, the addition of pembrolizumab to CP resulted in a sustained OS benefit despite substantial post study ICI use. In the pMMR population, an 11.8 month OS advantage was observed, despite at least 57% of the placebo patients receiving post study ICI. This data further supports the current US FDA approved indication of this regimen in the treatment of advanced stage or recurrent endometrial cancer irrespective of MMR status. Clinical trial information: NCT03914612 .