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Thromboembolic events in patients with advanced non-small cell lung cancer receiving palliative chemoimmunotherapy with pembrolizumab.

e24068 Background: Thromboembolic events (TEEs) represent a serious and clinically significant complication in patients (pts) with cancer undergoing systemic treatment. The incidence of TEEs in pts with non–small cell lung cancer (NSCLC) receiving palliative chemotherapy has been reported to range from 6 to 30%. However, data on the incidence and characteristics of TEEs associated with palliative chemoimmunotherapy remain limited. Methods: In this retrospective, single-center study, we analyzed TEEs in 192 pts with NSCLC who initiated palliative pembrolizumab-based chemoimmunotherapy between January 2019 and August 2024. Treatment regimens consisted of pembrolizumab combined with pemetrexed and platinum (n=128) or paclitaxel and carboplatin (n=64). TEEs occurring during chemoimmunotherapy or within six months after treatment discontinuation were included, while events following a change of regimen were excluded. Results: TEEs occurred in 27 patients (14%, pemetrexed: 21, paclitaxel: 6), including two fatal events, both of which were myocardial infarctions. Pulmonary thromboembolism was the most common TEE (n=9), followed by deep vein thrombosis (n=7). TEEs occurred at a median of 106 days (range, 3–838 days) after initiation of chemoimmunotherapy. No significant factors, including the Khorana score and regimens, were identified to be associated with the occurrence of TEEs. Conclusions: In real-world practice, the incidence of TEEs in pts with NSCLC receiving palliative pembrolizumab-based chemoimmunotherapy was higher than that reported in phase III trials. Therefore, careful surveillance for TEEs during chemoimmunotherapy, with consideration of anticoagulation in high-risk pts, may be warranted.

Clinicopathologic features, treatment patterns, and outcomes in young women with metastatic breast cancer: A National Cancer Database analysis.

1115 Background: Young women with metastatic breast cancer (MBC) represent a distinct and understudied population and often present with aggressive disease features. However, population-level studies characterizing clinicopathologic features, treatment patterns, and outcomes in this group remain limited. Methods: The National Cancer Database (NCDB) was queried to identify women diagnosed with MBC. Patients were stratified by age (<40 vs ≥40 years). Baseline characteristics were compared using chi-square tests. Overall survival (OS) was assessed using Kaplan–Meier analysis and compared using log-rank tests. Multivariable Cox regression was performed to evaluate independent associations with OS. Results: Among 59,213 women with MBC, 4,406 (7.4%) were aged <40 years. Median follow-up was 25.3 months (IQR 9.3–42.1). Compared with women ≥40, young women had more grade III tumors (61.0% vs 50.4%), lymphovascular invasion (44.2% vs 31.7%), and liver metastases (35.3% vs 23.5%). Young women were also more likely to receive chemotherapy (44.6% vs 21.7%), immunotherapy (44.2% vs 27.2%), radiation (39.3% vs 29.8%), and surgery of the primary tumor (26.7% vs 13.3%), whereas receipt of hormonal therapy was lower compared to their older counterparts (56.9% vs 54.8%). Receptor subtypes in young women were distributed as follows: HR+/HER2+ (22.6%), HR+/HER2- (50.8%), HR-/HER2+ (11.0%) and TNBC (15.5%). Young women demonstrated longer median OS compared with those ≥40 (68.7 months [95% CI 65.2–74.6] vs 37.1 months [95% CI 36.4–37.7]). TNBC had the worst OS among receptor subtypes (p<0.0001), with more than three-fold mortality risk compared with HR+/HER2- (HR 3.65, 95% CI 3.22–4.15). Metaplastic histology was associated with inferior OS compared to IDC (HR 3.11, 95% CI 1.72–5.64), and Black race was associated with worse OS compared to White race (HR 1.65, 95% CI 1.47–1.87). Receipt of radiation (HR 0.75, 95% CI 0.67–0.84), immunotherapy (HR 0.59, 95% CI 0.53–0.66), hormonal therapy (HR 0.42, 95% CI 0.38–0.47), and surgery to the primary site (HR 0.42, 95% CI 0.37–0.49) were associated with improved OS, whereas chemotherapy was not associated with OS. Most patients had a single metastatic site (55.5%), among which bone was the most common site (59.8%), followed by liver (18.4%), lung (7.7%), and brain (1.6%). Compared to bone-only metastases, brain (HR 2.04, 95% CI 1.17–3.56), lung (HR 2.08, 95% CI 1.58-2.74), and distant lymph node involvement (HR 1.54, 95% CI 1.18–2.00) were associated with worse OS. Conclusions: In this largest population-level study to date, young women with MBC presented with more aggressive disease features, yet demonstrated better OS compared with older patients. Survival outcomes were associated with receptor subtype, histology, and metastatic site. These findings provide valuable insights to guide clinical management of young women with MBC.

“When I’m translating, I’m a daughter as well”: Perspectives of caregivers supporting patients with limited language proficiency.

12096 Background: Family caregivers of people with advanced cancer provide essential support but often experience significant emotional distress. Caring for patients with limited language proficiency (LLP) introduces additional, distinct challenges. Patients with advanced cancer and LLP experience barriers to access and quality of care and advance care planning, resulting in increased reliance on family caregivers even when professional language services are available. This study explored the experiences and challenges of caregivers supporting advanced cancer patients with LLP to inform future interventions aimed at improving patient and caregiver outcomes. Methods: Caregivers supporting patients with advanced cancer and limited English proficiency treated at the Princess Margaret Cancer Centre (Toronto, Canada) were recruited via clinician referral and study flyers. Participants completed semi-structured interviews or focus groups exploring healthcare navigation, interpreter use, support needs, and recommendations for service improvement for patients with LLP. Transcripts were analyzed iteratively using practical thematic analysis. Results: Ten caregivers (ages 34–63; 6 female, 4 male; 2 spouses, 8 adult children; 5 supporting Chinese-speaking patients) participated. Participants acted as informal interpreters and mediators between patients and providers, a form of ‘language brokering’ that added substantial emotional and cognitive burden. Their experiences are subsumed under 4 interrelated themes: 1) Protective buffering and information gatekeeping: caregivers often filtered or withheld prognosis and end-of-life information to protect patients’ emotional well-being or align with cultural values; 2) Interpreter use representing both relief and loss of control: professional interpretation reduced linguistic burden but created new concerns regarding privacy, cultural sensitivity, and control over sensitive discussions; 3) Constant vigilance: caregivers felt constant pressure to monitor and understand patients’ symptoms and preferences, communicate them to providers, and support patient understanding and reassurance; and 4) Invisibility of caregiver needs: caregivers rarely recognized or prioritized their own needs, framing language brokering and caregiving as an expected familial or cultural duty. Conclusions: Family caregivers supporting patients with advanced cancer and LLP perform substantial emotional and cognitive labor that remains largely unrecognized in clinical practice. Interventions such as consistent and proactive access to professional interpreters and multilingual educational resources delivered across multiple modalities may support both patients and caregivers. These findings highlight an under-recognized but critical dimension of equitable, patient-centered oncology care.

Dose-dependent effect of dinutuximab-IR700 photoimmunotherapy on GD2-expressing tumors.

e14556 Background: Near-infrared photoimmunotherapy (PIT) is a novel, molecularly targeted cancer therapy. It combines tumor-directed immunotherapy agents with a phthalocyanine dye IR700 to induce rapid cell death upon light activation, while sparing adjacent normal tissue. GD2 is a targetable tumor-associated antigen expressed in neuroblastoma, osteosarcoma and glioblastoma. Dinutuximab, an anti-GD2 monoclonal antibody, has demonstrated clinical efficacy in neuroblastoma immunotherapy. We evaluated the efficacy of Dinutuximab-IR700 as a targeted PIT agent in in vitro models of GD2-expressing tumors. Methods: We synthesized a Dinutuximab-IR700 antibody dye conjugate (ADC) and tested it on human-derived SK-N-BE(2) and NMB6 (neuroblastoma), LM7 and 143B (osteosarcoma), U87 (glioblastoma) and mouse-derived GL261 and SB28 (glioblastoma) cell lines. For PIT, cells were incubated with ADC (15 μg/mL), followed by activation with light at 10-100 J/cm 2 at 150 mW/cm 2 . Controls included untreated, light-only and ADC-only groups, along with apoptosis (camptothecin) and necrosis (H 2 O 2 ) positive controls. Additional ADC doses of 5, 10 and 20 μg/mL were evaluated in neuroblastoma. Cell death was evaluated by Annexin V/Propidium Iodide (PI) flow cytometry, and brightfield/fluorescence microscopy at 24 h and 48 h post-PIT. GD2 expression per cell for each cell line was also quantified by flow cytometry to correlate with PIT response. Results: Dinutuximab-IR700 PIT markedly reduced cancer cell viability in both neuroblastoma cell lines by up to 78%. Light and ADC had dose-dependent effects on cell death, plateauing at 50 J/cm 2 and 15 μg/mL, respectively. PIT efficacy on osteosarcoma cell lines was heterogeneous, with up to 14% cell death observed only in LM7. PIT was not effective in U87, GL261 and SB28 glioblastoma cells, which showed minimal ADC binding on fluorescence microscopy. Cell death by PIT strongly correlated with GD2 expression per cell across tumor cell lines. Light-only and ADC-only groups matched untreated controls. PIT efficacy was similar with different degrees of labeling (2 vs 3 IR700 molecules per Dinutuximab molecule). Annexin V/PI staining indicated apoptosis over necrosis as the primary mode of cell death, supported by microscopy. Dinutuximab-IR800, studied for intraoperative molecular imaging, was ineffective under identical conditions, demonstrating IR700’s unique utility for PIT. Conclusions: GD2-targeted Dinutuximab-IR700 PIT induces profound dose-dependent cytotoxicity across neuroblastoma cell lines, with variable activity in osteosarcoma and none in glioblastoma. The precise mechanism of action of PIT and reasons for its heterogeneous efficacy in different GD2-expressing tumors remain to be elucidated. This represents a novel precision medicine approach to neuroblastoma treatment, particularly for residual disease after surgical resection.

Safety and efficacy of chemotherapy in metastatic colorectal cancer with liver dysfunction due to hepatic metastases: A systematic review.

e15620 Background: Patients with metastatic colorectal cancer (mCRC) and severe hepatic dysfunction from liver metastases are routinely excluded from trials, leaving limited evidence to guide chemotherapy dosing, safety, and expected benefit. Methods: MEDLINE and Embase were searched from inception to January 15, 2026. We included English-language reports of adults with mCRC and liver dysfunction attributed to hepatic metastases who received cytotoxic chemotherapy (fluoropyrimidine-, oxaliplatin-, and/or irinotecan-based regimens; biologics allowed). Data were extracted in by two independent reviewers. Outcomes included grade ≥3 toxicity, treatment-related mortality, bilirubin response, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Where reported, individual patient data (IPD) were pooled for descriptive analyses and Kaplan–Meier estimation. Results: Of 6775 records screened, fourteen reports were included and provided extractable IPD for 33 patients. Median baseline bilirubin was 7.4 mg/dL (range 1.9–28.1). Most patients received oxaliplatin-based therapy (25/33, 76%); upfront dose reductions were common (25/28, 89%), with subsequent dose escalation in 19/25 (76%) when reported. A ≥50% bilirubin reduction occurred in 25/32 (78%), and bilirubin normalized ( < 1.3 mg/dL) in 18/32 (56%); median time to normalization was 56 days (IQR 39–67; n = 11). Among patients with safety reporting, grade ≥3 adverse events occurred in 9/21 (43%) and treatment-related mortality in 1/22 (4.5%). ORR was 10/20 (50%) among patients with response assessment. In available IPD, Kaplan–Meier median PFS was 7.3 months (n = 22) and median OS 8.2 months (n = 30). Conclusions: In the sparse evidence available for this high-risk population, chemotherapy—most often initiated at reduced dose and escalated as liver function improved—was frequently associated with biochemical improvement and occasional objective responses, with uncommon reported treatment-related mortality. Given substantial reporting limitations and small study sizes, there is potential for reporting bias, and prospective data are needed. Nonetheless, these findings suggest that severe hyperbilirubinemia due to tumor burden should not automatically preclude cautious, individualized initiation of systemic chemotherapy with close monitoring in selected patients.

Enabling hybrid AI–radiologist endpoints in clinical trials imaging workflows.

2019 Background: Imaging endpoints in oncology clinical trials commonly rely on a 2 + 1 radiologist reading paradigm, in which two independent readers perform primary assessments and a third adjudicates disagreements. This model underpins response evaluation frameworks such as RECIST and RANO, but is resource-intensive and contributes to trial cost, operational complexity, and inter-reader variability. Advances in transformer-based deep learning for 3D medical imaging enable hybrid AI–radiologist workflows that may preserve adjudicated oversight while reducing primary human reads. We evaluated the feasibility of replacing one primary radiologist reader with AI in a hybrid 2+1 imaging workflow, using glioma segmentation as a representative use case and with consideration for near-term integration into clinical trial imaging platforms such as Voiant Hub. Methods: A 3D SwinUNETR open-source deep learning model implemented using the MONAI framework pre-trained to segment glioma subregions from multimodal MRI, including enhancing tumor and non-enhancing/edema components. Model performance was assessed using Dice similarity coefficients across a multi-case dataset, complemented by qualitative review of representative cases spanning high-agreement and high-discordance scenarios. Two reading paradigms were evaluated conceptually: (1) traditional radiologist–radiologist + adjudicator, and (2) AI–radiologist + adjudicator. AI–radiologist segmentation divergence was used as a proxy for adjudication likelihood and workflow impact. Results: AI segmentation demonstrated substantial concordance with reference contours in well-defined enhancing tumor regions, with performance variability reflecting known biological heterogeneity. Dice scores for enhancing tumor reached values as high as 0.80, with a broad distribution across cases. Qualitative review showed that AI–radiologist disagreements were most commonly associated with small-volume lesions, infiltrative margins, or low-contrast regions: patterns similar to known human inter-reader variability. The presence of an adjudicator preserved clinical oversight for discrepant cases while eliminating the need for a second full human primary read. Conclusions: A hybrid AI–radiologist 2+1 imaging workflow is feasible for glioma volumetric assessment and has broader implications for RECIST- and RANO-based endpoints in oncology clinical trials. Substituting AI for one primary radiologist reader preserves adjudicated decision-making while reducing manual read burden. The availability of configurable, regulator-aligned imaging platforms such as Voiant Hub positions this hybrid approach as a near-term, easily adoptable evolution of current reading paradigms. Prospective evaluation is warranted to quantify operational impact, adjudication rates, and endpoint consistency across solid tumor and neuro-oncology trials.

Breast cancer mortality among patients with mental and behavioral disorders in the United States: An age-stratified national analysis (1999–2023).

e13091 Background: Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer-related mortality among women in the United States. Mental and behavioral disorders (MBDs) are increasingly recognized as contributors to disparities in cancer screening, treatment adherence, and survival. However, population-level, age-stratified patterns of MBD-associated breast cancer mortality remain poorly characterized. Methods: We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population using the CDC WONDER database (1999–2023) for breast cancer (ICD-10: C50) deaths with co-occurring mental and behavioral disorders (ICD-10: F01–F99). Joinpoint regression models were applied to estimate annual percent change (APC) and identify significant temporal trends. Results: From 1999 to 2023, a total of 107627 deaths were reported among breast cancer patients with mental and behavior disorders. The overall AAMR increased from 0.9 in 1999 to 2.4in 2023 (AAPC: 3.74; 95% CI: 2.98 to 4.52; p < 0.001). The most pronounced increase was observed between 1999 and 2006 (APC: 8.29; 95% CI: 5.57 to 11.08; p < 0.001), followed by a continued and marked rise through 2023 (APC: 1.93; 95% CI: 1.52 to 2.33; p < 0.001). Older adults accounted for the majority of deaths (n = 89,974). Women consistently demonstrated a higher annual increase in mortality compared with men (AAPC: 4.11% vs. 0.00%). The highest AAMRs were observed among non-Hispanic Black and non-Hispanic White individuals, while the lowest rates occurred among Hispanic individuals; however, non-Hispanic White individuals exhibited the highest AAPC (3.96%). Geographic disparities were evident, with the South experiencing the greatest increase in mortality and the West the least. Metropolitan areas showed a steeper rise compared with non-metropolitan areas. Conclusions: This national, age-stratified analysis reveals a disproportionate burden of breast cancer mortality among individuals with co-occurring mental and behavioral disorders, particularly in older age groups. These disparities likely reflect gaps in screening, timely diagnosis, treatment access, and continuity of care. Average Annual Percentage Change (AAPC) per 100,000 population for trends in breast cancer and mental and behaviour disorders from 1999 to 2023. Variable AAPC (95%CI) P-Value Overall 3.74( 2.97– 4.52) < 0.000001 Male 0 < 0.000001 Female 4.10( 2.70– 5.52) < 0.000001 NH Blacks 3.88( 2.85 – 4.92) < 0.000001 Hispanic 3.36( 2.51– 4.23) < 0.000001 NH White 3.96( 3.08– 4.86) < 0.000001 West 3.40 (1.53 to 5.30) = 0.000319 Northeast 3.45 (2.59 to 4.32) < 0.000001 South 4.61(3.56 to 5.68) < 0.000001 Midwest 3.78(2.97 to 4.60) < 0.000001 Metropolitan areas 3.75(2.74 to 4.77) < 0.000001 Non metropolitan areas 5.16(3.78 to 6.56) < 0.000001

Visualization of grout diffusion in coarse-grained materials using transparent soil: Effects of Fine particle content

Fine-particle loss in earth-rock dams can induce abnormal grout diffusion during rehabilitation. To address this issue, we investigated the influence of fine particle content on grouting efficiency in coarse-grained materials. Using transparent soil technology, coarse-grained materials were simulated with fused quartz sand and a refractive-index-matched pore fluid (n = 1.4585). Dyed epoxy resin was used as a cement grout analog. Constant-pressure grouting tests (40 kPa) were performed on three test conditions representing no fine-particle loss, partial fine-pareicle loss, and complete fine-particle loss. The grout diffusion process was visualized and quantified using Particle Image Velocimetry (PIV). The results reveal that fine particle content critically controls grout diffusion patterns and rates. (1) Excessive fines cause pore clogging, resulting in grout upwelling, surface seepage, and limited diffusion, forming locally consolidated masses with blocky bonding. (2) An appropriate fine particle content enables uniform spherical diffusion, creating an optimized structure characterized by point bonding of large particles and small-pore filling. (3) The absence of fines leads to gravity-dominated rapid settlement with weak horizontal diffusion, leaving only surface-coated particles. This study elucidates the coupled mechanisms of fine-particle migration, clogging, and grout diffusion, providing an experimental basis for optimizing permeation grouting in coarse aggregates.

Conformational Landscapes in the Ground and Excited States Dictate Circularly Polarized Excimer Emission: A Thermodynamic–Kinetic Interplay in Carbazole Dimer Systems

ABSTRACT We demonstrate that in chiral carbazole dimers, the tt conformer generates intense excimer CPL, while gauche rotamers yield only local emission. In 1a , CPL intensifies and red‐shifts upon cooling due to greater tt contribution. In contrast, the tert ‐butyl derivative 1b shows weak, temperature‐insensitive CPL owing to enhanced accessibility of non‐CPL‐emissive gauche conformers. This work reveals how subtle substituent and environmental effects modulate excited‐state conformational dynamics and chiroptical responses through a thermodynamic–kinetic interplay.

Toward robust stretchable OLEDs: Unifying light extraction and mechanical compliance via random micro-/nanostructuring

The advancement of flexible and stretchable optoelectronics has long been limited by two fundamental challenges. The first is inefficient light extraction caused by photon trapping in waveguide modes, and the second is the inherent trade-off between optical performance and mechanical durability. Here, we report a cost-effective and scalable elastomeric substrate with randomly distributed micro-/nanostructures fabricated by a sandpaper-templated replication process. These substrates achieve high optical transmittance (>91%) with widely tunable haze. Their randomly distributed structures reduce internal reflection and generate a near-Lambertian emission profile, thereby significantly enhancing light outcoupling. When integrated into flexible white organic light-emitting diodes (OLEDs), the optimized substrates improved light extraction efficiency by 48%, attaining a peak current efficiency of 127.5 cd/A. Moreover, the devices exhibit robust mechanical and environmental stability, retaining more than 90% of their initial luminance after 2500 bending cycles and 30 min of water immersion. Intrinsically stretchable OLEDs fabricated on these substrates maintain stable operation under 50% strain, satisfying application needs that demand extensibility beyond conventional flexibility. The proposed strategy offers a scalable route to wearable and implantable optoelectronics with improved optical, mechanical, and environmental robustness.

Advancing chronic obstructive pulmonary disease treatment with inhaled nano-carrier systems

Harnessing ER-associated degradation to target transmembrane proteins

Cold Atmospheric Plasma‐Activated Decellularized Extracellular Matrix Gel as a Tumor‐Infiltrating Immunoactivation Platform for Post‐Surgical Cancer Immunotherapy (Adv. Mater. 34/2026)

Asymmetric Rolling‐Up Induced Strong Polarization Electric Field for Ultrahigh Areal Electrochemical Capacitance

ABSTRACT Electrochemical capacitors are promising candidates for large‐scale energy storage devices owing to their high power densities. However, as increasing their energy densities with high‐loading thick electrodes, the ion transport kinetics are usually limited during cycling. Here, asymmetric roll‐ups of transition metal carbides (MXenes) are fabricated via a modified stiffness‐mediated rolling‐up strategy. Such asymmetric structure induces an electron concentration gradient along the axis of MXene roll‐up, leading to a strong polarization electric field. Under the polarization, ionic transport conductance of the asymmetric MXene roll‐up in various ions (e.g., H + , Li + , Na + , NH 4 + , Zn 2+ , Mg 2+ , Al 3+ ) is up to ∼10 2 µS, which is an order of magnitude higher than the constituent building blocks (∼10 1 µS). As a result, the film constructed from asymmetric MXene roll‐up exhibits an ultrahigh rate capability of ∼400 F g −1 at 5000 mV s −1 and unique thickness‐independent capacitive features. Moreover, the areal capacity of the 400‐µm‐thick MXene roll‐up film with a high mass loading of ∼50 mg cm −2 is up to ∼26 F cm −2 , outperforming the most reported materials.

Investigation of singular and simultaneous faults in rotating machines using the finite element method

Abstract Rotating machinery failures continue to impose substantial economic, operational and safety risks across critical industries such as power generation, manufacturing, oil and gas, and aerospace, where unplanned downtime can severely disrupt production and elevate maintenance costs. This study addresses a critical gap in the field of failure management by providing a comprehensive, physics‑based investigation into the dynamic behaviour of rotating machines subjected to simultaneous rotor faults. These conditions closely reflect real industrial environments yet remain insufficiently explored in the literature. A finite element (FE) model based on Timoshenko beam theory is developed, calibrated, and validated using experimental modal and vibration data from a laboratory-scale two-stage rotor rig. Five common defects -unbalance, misalignment, shaft bow, pedestal looseness, and partial rotor rub- are examined in combined scenarios to evaluate their interactions and influence on system dynamics. The validated FE model successfully reproduces the characteristic vibration signatures observed experimentally, including harmonic responses associated with unbalance and misalignment, eccentricity‑driven amplification due to shaft bow, intermittent impact behaviour from looseness, and super harmonics and chaotic components arising from rub. The study reveals insights into how coupled faults modify dynamic responses, including location‑specific amplification near natural frequencies, speed‑dependent shifts in the dominant harmonics, and impulsive responses driven by rub-bow interactions. The findings offer significant potential for advancing vibration‑based condition monitoring, providing a foundation for improved feature selection in intelligent diagnostic systems and supporting the development of robust, physics‑informed approaches for managing rotor‑related faults in industrial machinery.

S-acylation and membrane localization of the small GTPase ARL15 are mediated by the Golgi S-acyltransferases ZDHHC7 and ZDHHC3

Neoadjuvant cadonilimab plus CapeOX in patients with clinical stage III gastric or esophagogastric junction adenocarcinoma (GC/EGJC): A prospective, single-arm phase II study.

4089 Background: Perioperative PD-L1 inhibitor plus chemotherapy has shown survival benefit in PD-L1-positive patients with locally advanced GC/EGJC. However, evidence for neoadjuvant PD-1/CTLA-4 bispecific blockade remains limited. This study evaluates neoadjuvant cadonilimab plus CapeOX in patients with clinical stage III GC/EGJC. Methods: This prospective, single-arm phase II study (NCT06310473) enrolled patients (pts) with cT3-4aN1-3M0 disease (AJCC 8th), staged by contrast-enhanced CT and staging laparoscopy with peritoneal cytology to exclude peritoneal metastasis and positive peritoneal cytology (CY1). Pts received cadonilimab (10 mg/kg) plus standard-dose CapeOX every 3 weeks for 3 cycles. Pts without progressive disease on repeat CT and laparoscopy underwent curative-intent surgery, followed by 3-5 cycles of adjuvant CapeOX. The primary endpoint was the pathologic complete response rate (pCR, defined as no residual tumor in stomach and lymph node). The data cutoff was January 15, 2026. Results: From May 2024 to August 2025, 30 pts with GC/EGJC were enrolled (GC, n = 21; EGJC, n = 9); 83.3% (25/30) were cT4a and 73.3% (22/30) were cN2-3. PD-L1 CPS < 1 was observed in 14.8% (4/27) of evaluable pts. All pts completed 3 neoadjuvant cycles. Three pts did not undergo surgery: one refused resection and subsequent antitumor therapy after achieving a cCR to neoadjuvant therapy; one had a PR and continued systemic therapy; and one had PD with liver invasion on repeat laparoscopy and initiated second-line therapy. The other 27 pts underwent resection; one had CY1 on postoperative assessment and was considered PD, with an R0 resection rate of 96.3% (26/27). The pCR and major pathologic response (MPR) rates were 22.2% (6/27) and 37.0% (10/27), respectively. The tumor downstaging rate was 74.1% (20/27), including a ypN0 rate of 55.6% (15/27). Adjuvant therapy was administered in 23/27 (85.2%), with four pts still on therapy. Treatment-related adverse events occurred in 100% (30/30), including grade≥3 events in 20.0% (6/30). Notable events included one perioperative cardiovascular death (G5); one pulmonary embolism (G3) diagnosed 5 weeks postoperatively that resolved with anticoagulation; one patient with concomitant anastomotic leakage (G4), intra-abdominal infection (G4), and immune-related adrenal insufficiency (G2) who recovered after endoscopic covered-stent placement and conservative management; additional G3 events included ascites, neutropenia, and peripheral neuropathy (n = 1 each). No postoperative recurrence was observed among resected pts at data cutoff. Conclusions: Neoadjuvant cadonilimab plus CapeOX appears safe and effective in patients with clinical stage III GC/EGJC, achieving a moderate pCR rate and warranting further exploration of neoadjuvant immunochemotherapy combination strategies. Clinical trial information: NCT06310473 .

Thalamic neuroepithelial cysts: Endoscopic management strategies and clinical outcomes.

e14046 Background: Thalamic neuroepithelial cysts are rare congenital lesions that can cause significant neurological morbidity through direct parenchymal compression or obstruction of cerebrospinal fluid pathways. Due to their rarity, optimal surgical management strategies remain poorly defined. This study presents our institutional experience with endoscopic fenestration for symptomatic thalamic cysts. Methods: . We conducted a retrospective review of patients with thalamic or parathalamic cysts treated at the Hospital of the University of Pennsylvania between 2014 and 2024. Patient demographics, clinical presentations, imaging characteristics, surgical approaches, and outcomes were analyzed. Treatment strategies included observation, endoscopic fenestration with or without third ventriculostomy, stereotactic procedures, and open craniotomy. Results: Nine patients (mean age 47.88±13.02 years, 77.8% female) were identified. Five patients with asymptomatic cysts underwent observation without intervention. Three symptomatic patients underwent endoscopic fenestration, two with concurrent third ventriculostomy for hydrocephalus. All fenestration procedures achieved technical success with complete symptom resolution and no recurrences. One patient with atypical imaging features underwent craniotomy, revealing cystic glioma. Mean hospital stay for endoscopic procedures was 1.5 days with no complications. Conclusions: Endoscopic fenestration is a safe and effective treatment for symptomatic thalamic neuroepithelial cysts. Surgical approach selection should be guided by cyst location relative to cerebrospinal fluid spaces, with frontal transcortical trajectories preferred for cysts abutting the third ventricle and lateral infratentorial approaches for posterior lesions. Asymptomatic cysts with benign imaging characteristics can be safely managed with surveillance imaging.

Outcomes of neoadjuvant checkpoint inhibitor therapy followed by definitive chemoradiation in locally advanced head and neck squamous cell carcinoma (HNSCC).

e18014 Background: Approximately 70,000 Americans are diagnosed with HNSCC annually. While the KEYNOTE-689 trial established the benefit of neoadjuvant pembrolizumab in surgical candidates, its role in patients transitioning to definitive chemoradiation (CRT) for organ preservation requires further validation. This study evaluates the clinical outcomes, safety, and feasibility of neoadjuvant immune checkpoint inhibitor (ICI) therapy ± platinum/taxane-based chemotherapy in patients with locally advanced (LA) HNSCC undergoing definitive CRT. Methods: We conducted a retrospective cohort analysis of patients with LA-HNSCC at Mount Sinai Hospital. Inclusion criteria: new malignancy treated with 2–3 cycles of neoadjuvant ICI ± chemotherapy followed by definitive CRT (standard cisplatin/carboplatin with concurrent radiation). The primary endpoint was Overall Response Rate (ORR) via RECIST. Secondary endpoints included progression-free survival (PFS) and safety. Results: Of 132 patients receiving neoadjuvant therapy, 25 transitioned to definitive CRT (median age 63.6 years; 42% HPV+). Within this cohort, 76% received combination ICI + chemotherapy as induction, while 24% received ICI monotherapy. The post-neoadjuvant ORR was 83.3% (CR: 16.7%; PR: 66.7%). Neoadjuvant therapy did not delay the initiation of definitive CRT in any patients. Safety was favorable; only two patients (8%) experienced Grade 3+ toxicities during the neoadjuvant phase. At a median follow-up of 7.8 months, the 6-month PFS was 91.0%. Notably, a Combined Positive Score (CPS) >=1 was associated with significantly deeper radiological responses compared to CPS < 1 (p < 0.05). Conclusions: Neoadjuvant ICI and chemotherapy followed by definitive CRT is a feasible and well-tolerated strategy for LA-HNSCC. These findings suggest that induction immunotherapy does not compromise the delivery of definitive local therapy and provides promising early oncologic outcomes, particularly in CPS-positive disease.

Molecular biomarker testing to predict outcomes in gliomas: A SEER registry study in Kentucky.

e14095 Background: Molecular testing has been required since 2021 for the diagnosis of many primary CNS tumors, and in 2018 US cancer registries implemented molecular site-specific data items. With increasing approval of targeted therapies, molecular testing is essential for improving outcomes. We reviewed biomarker completeness in a population-based registry in Kentucky to assess integration of molecular testing into practice and its impact on survival. Methods: We analyzed first primary brain tumors diagnosed from 2018 to 2023 from the Kentucky Cancer Registry, a SEER registry. Using Brain Molecular Markers (Data Item #3816), biomarker completeness was categorized as complete (codes 01-09), not applicable (code 85, information not collected), or incomplete (codes 87, 99, missing). Markers examined included IDH, 1p/19q co-deletion, and MGMT methylation. Descriptive statistics were used to compare patients’ characteristics by completion status. Log-rank tests were performed to assess the significant differences by molecular marker status for glioblastoma, diffuse astrocytoma, and oligodendroglioma separately; case number, median and one-year survival are reported. Results: In 1,802 cases of primary brain tumors, 62.5% had complete biomarkers, 15.5% not applicable, and 22.0% incomplete. Complete cases were predominantly high-grade (87.7%) and glioblastoma (74.7%). Incomplete cases were more frequent from 2018-2020 (54.8%), age ≥65 (51.5%), and non-glioblastoma (55.3%). Among cases where molecular testing was not applicable, over half were young 0-19 (51.4%) with low-grade tumors (44.4%). In glioblastoma, incomplete coding demonstrated worse survivals (N=175, median 2.6 mo, 16.7% 1-yr survival) versus IDH-wildtype (N=841, 9.1 mo, 40.9%, respectively). For oligodendroglioma, IDH-mutant/1p/19q co-deleted had excellent prognosis (N=92, median not reached, 97.8% 1-yr survival) versus incomplete (N=8, 50.0% 1-yr survival). For diffuse astrocytoma, IDH-mutant demonstrated superior survival (N=79, median not reached, 94.9%) while incomplete (N=28, median 50.3 months, 67.9%) fared worse. All between-group comparisons were statistically significant (log-rank p<0.05). Conclusions: Cases not having molecular testing are common and have worse outcomes. Our findings demonstrate primary brain tumor patients would benefit from a widespread initiative to increase molecular testing to ensure correct diagnosis and treatment.