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Anomalous thermal expansion and magnetic critical behavior in ErFe12− <i>x</i> Ti <i>x</i>

Rare-earth-transition-metal compounds with a ThMn12-type structure exhibit high Curie temperature (TC), large saturation magnetization, and tunable magnetic anisotropy, making them promising for permanent magnets and multifunctional magnetoelastic materials. In this work, we systematically investigated the zero thermal expansion (ZTE) behavior, magnetoelastic coupling mechanism, and magnetic critical behavior of ErFe12−xTix (x = 1.0, 1.1) using temperature-dependent neutron powder diffraction, magnetic measurements, and thermal dilatometry. The results demonstrate that ErFe10.9Ti1.1 exhibits excellent ZTE properties over 447–507 K. Rietveld refinement indicates that the ZTE originates from the pronounced spontaneous volume magnetostriction (ωs) induced by strong magnetoelastic coupling near TC. Critical behavior analysis reveals that the system undergoes a second-order magnetic transition dominated by long-range exchange interactions. Due to the weakening of long-range magnetic order and residual non-phononic volume contributions, a distinct deviation exists between the macroscopic characteristic temperature (TZTEend ≈ 507 K) and the microscopic lattice characteristic temperature (T* ≈ 525 K) of the system.

In vitro and in vivo toxicological evaluation of zein/gum arabic nanoparticles loaded with pyridoxine and cyanocobalamin

Bidirectional Brain‐Machine Communication and Neuromodulation by Supramolecular Hydrogel Neural Probes for Chronic Pain Management

ABSTRACT Chronic pain continues to pose a significant therapeutic challenge due to its complex pathophysiology and the limited efficacy of conventional pharmacological treatments. Brain‐machine interfaces (BMIs) have emerged as a promising strategy for recording neural activity, modulating neural circuits, and treating neurological disorders. However, the long‐term performance of conventional rigid implantable probes is severely constrained by their mechanical mismatch with soft brain tissue. This mismatch provokes chronic inflammatory responses and results in gradual signal deterioration. Additionally, most existing probes lack integrated functionality for simultaneous in situ neuromodulation and neural signal recording. In this work, we developed a supramolecular hydrogel based on α‐helical polypeptide cross‐linkers, achieving an optimal balance of mechanical compliance, electrical conductivity, and optical transparency. When implanted in the rat prelimbic cortex, the hydrogel probe enabled stable recording of local field potentials (LFPs) for up to 16 weeks. Importantly, the probe enabled in situ neuromodulation while concurrently recording evoked LFPs, resulting in enhanced prelimbic cortical activity, increased mechanical withdrawal thresholds, and reduced cold allodynia in a chronic neuropathic pain model. These findings advance neural interface technology by enabling integrated, long‐term monitoring and neuromodulation, representing a paradigm shift in the design of implantable devices for chronic pain therapy.

FM-Mamba: end-to-end non-causal Mamba-based network for efficient flood mapping

Actin’s functional “switch”: Constraining C-terminal conformational flexibility disrupts functionally important communication networks

Effects of multimodal local therapy on survival in gastric cancer leptomeningeal metastases.

e14022 Background: Leptomeningeal metastasis (LM) from gastric cancer represents a terminal condition with poor prognosis, where the efficacy of systemic therapy is limited by the blood-brain barrier. While local strategies such as whole-brain radiotherapy (WBRT), intrathecal (IT) chemotherapy, and surgical decompression (e.g., VP shunt, EVD) are utilized, the clinical impact of combining these modalities remains under-investigated. We evaluated the real-world safety and survival outcomes of this multimodal strategy. Methods: We analyzed 15 patients with gastric cancer LM treated at Guangdong Sanjiu Brain Hospital. Treatment regimens integrated systemic therapy with distinct local therapeutic modalities and their combinations, including WBRT, IT chemotherapy, and neurosurgical interventions (Ommaya reservoir, VP shunt, or EVD). The primary endpoint was overall survival (OS) from the diagnosis of LM. Survival outcomes were assessed using Kaplan-Meier methods and Log-rank tests. Safety was graded according to CTCAE v5.0. Results: The median OS for the entire cohort was 6.9 weeks. The multimodal regimen demonstrated a favorable safety profile; no Grade 3-4 adverse events were recorded. Toxicities were predominantly Grade 1-2 hematologic. Device-related complications occurred in 13.3% of patients and were manageable. Analysis of specific modalities revealed significant survival benefits. The addition of WBRT conferred a highly significant survival extension compared to non-WBRT regimens (median OS: 7.7 vs. 3.5 weeks; Log-rank P = 0.0024). Similarly, patients receiving IT chemotherapy exhibited superior survival compared to the non-IT group (8.7 vs. 4.6 weeks; P = 0.045). The "Combined Local Therapy" cohort (comprising Surgery [VP shunt/EVD] + WBRT + IT) showed a strong trend toward improved survival compared to limited local therapy (9.9 vs. 5.4 weeks; P = 0.054). Furthermore, baseline CSF-CEA &lt;5 ng/ml was identified as a robust predictor of prolonged survival (24.6 vs. 6.0 weeks; P = 0.0299). Conclusions: Comprehensive multimodal therapy is feasible and safe for patients with gastric cancer LM, showing zero severe toxicity. The significant survival benefit observed with WBRT and IT chemotherapy suggests that restoring CSF flow and reducing intracranial tumor burden are critical components of management. The combination of surgical intervention (VP shunt/EVD), WBRT, and IT chemotherapy offers a promising therapeutic strategy that warrants further validation.

Impact of FGFR3 pathway activation in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

4596 Background: The prognostic value of FGFR3 pathway activation in patients with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) has not been established. Activation of FGFR3 signaling drives a subset of urothelial bladder cancers and classically results from pathogenic gene mutations (mut) or fusions (fus). Additionally, an RNA signature (FGFR-PRS) representing activation of the FGFR3 pathway independent from pathogenic FGFR3 mut or fus has been identified (Eisner et al. Clin Can Res 2024). We previously reported that high tumor mutational burden (TMB) may be associated with improved pathological complete response (pCR) and survival in a cohort of MIBC patients treated with cisplatin-based NAC (Burgess et al. GU ASCO ‘26). In the current analysis, we assessed the impact of FGFR3 pathway activation detected by either FGFR3 gene mut/fus or FGFR-PRS (+) on clinical outcomes in the previously reported cohort. Methods: 91 patients with MIBC who received cisplatin-based NAC followed by radical cystectomy underwent genomic analysis of diagnostic transurethral resection of bladder tumor specimens with the Tempus xT platform. Sample size was prespecified by statistical design. A subset of 61 patients had sufficient RNA for FGFR-PRS analysis. Correlation of FGFR3 molecular status with TMB and clinical outcomes was performed using logistic regression, Cox proportional hazards models, and Kaplan-Meier techniques. Results: Median follow up for the cohort was 63.6 months. pCR was achieved in 31.9%. 41.8% of patients relapsed. FGFR3 mut were found in 8 (8.8%) and included p.R248C (n = 2), p.S249C (n = 5), and p.G370C (n = 1). One (1.1%) patient had a FGFR3-TACC3 fus. In the subset with RNA analysis (n = 61), FGFR-PRS (+) was detected in 33 (54.1%), of which 28 (84.8%) were FGFR3 wild type (wt) without detected mut/fus. pCR occurred in 12.5% and 33.7% with and without FGFR3 mut [OR 0.281, p = 0.428]. pCR was similar regardless of FGFR-PRS status [OR 1.372, p = 0.602]. All tumors with FGFR3 mut/fus (n = 9) had TMB &lt; 10 Mut/Mb. Nineteen (57.6%) tumors with FGFR-PRS (+) had TMB &lt; 10 compared to 13 (46.4%) of FGFR-PRS (-) tumors. Six (75%) patients with FGFR3 mut [OR 3.188, p = 0.064] and 10 (30.3%) with FGFR-PRS (+) [OR 1.087, p = 0.999] relapsed. Patients with FGFR3 mut had inferior relapse-free survival (RFS) [HR 2.58, p = 0.028], but those with FGFR-PRS (+) did not [HR 1.37, p = 0.451]. Conclusions: The presence of FGFR3 mutations was associated with an inferior relapse rate and RFS in this MIBC cohort treated with cisplatin-based NAC. FGFR3 pathway activation by RNA signature (FGFR-PRS+) was not associated with inferior outcomes. Whether peri-operative FGFR3 inhibition improves prognosis in MIBC patients with FGFR3 mutations should be studied.

A phase II, single-arm, exploratory study of GEMOX combined with tislelizumab and donafenib in the perioperative treatment of potentially resectable intrahepatic cholangiocarcinoma with high recurrence risk.

TPS11199 Background: Biliary tract cancer (BTC) is characterized by strong invasiveness and poor prognosis, with a metastasis and recurrence rate of up to 67% within 1 year after surgery and a 5-year overall survival rate of only 5%~15%. Among BTC subtypes, intrahepatic cholangiocarcinoma (ICC) accounts for a relatively high proportion, and its unique biological behaviors result in persistently high postoperative recurrence risk, which seriously endangers patients' life and health. Currently, major guidelines recommend that patients with potentially resectable ICC at high recurrence risk participate in clinical trials to explore optimal treatment strategies. For patients evaluated as "technically resectable but with high-risk recurrence" before surgery, clinical practice has shown that neoadjuvant therapy can effectively eliminate micrometastases and reduce the difficulty of R0 resection; postoperative adjuvant therapy can further prevent recurrence. Therefore, we innovatively propose a perioperative treatment model aimed at breaking through the existing therapeutic predicament. Methods: This study is a phase Ⅱ, single-arm, exploratory study with a fixed sample size of 20 patients. The inclusion criteria are intrahepatic cholangiocarcinoma (ICC) (TNM stage T1-4, N0-1, M0)based on preoperative assessment, initial technical resectability per imaging, and at least one high - risk recurrence factor. High-risk recurrence factors include: tumor diameter &gt;5 cm, regional lymph-node positivity, satellite/multifocal lesions, radiological suspicion of diaphragmatic adhesion, CA19-9 &gt;200 U/ml, and an anticipated surgical margin &lt;1 cm on pre-operative imaging. Treatment involves two 21 - day cycles of GEMOX (gemcitabine 1000mg/m² on day 1 and 8, oxaliplatin 100mg/m² on day 1) with tislelizumab (200mg on day 1) and donafenib (0.2g orally twice daily). If investigators confirm patients meet surgical criteria (R0 resection expected), surgery follows 1 - 2 weeks post - treatment. Post - surgery, adjuvant therapy starts within 5 weeks. The regimen is capecitabine (1250mg/m² orally twice daily on days 1 -14) or S - 1 (40 -60mg orally twice daily on days 1 -14, weight - adjusted) plus tislelizumab (200mg on day 1) and donafenib (0.2g orally twice daily), repeated every 21 days for six cycles. Primary endpoint is event - free survival (EFS). Secondary endpoints are objective response rate (ORR) and disease control rate (DCR) per RECIST1.1, R0 resection rate, major pathological response rate(MPR, the proportion of patients who underwent radical surgery and had ≤10% residual viable tumor in the postoperative specimen), treatment completion rate, overall survival (OS), disease - free survival (DFS), and safety (treatment - related adverse events' incidence and severity). Clinical trial information: ChiCTR2500112067.

Socioeconomic disparities in access to biomarker testing for gastrointestinal cancers: A nationwide patient-reported outcomes analysis.

e23261 Background: Recent advancements in biomarker technology, in conjunction with growing patient awareness, are notably transforming cancer care in the United States. However, access remains stratified by geography and local resources or support. To address these disparities, the GI Cancers Alliance launched a comprehensive initiative, designed to both increase patient education on the critical role of biomarkers in personalized treatment plans, and rigorously identify systemic barriers impeding access within the gastrointestinal (GI) cancer community. Methods: This 12-month, mixed-methods patient-reported outcomes (PRO) study analyzed a group of 1,224 patients across all GI cancer indications. Methodologies included quantitative in-person and online surveys, concurrently with qualitative individual interviews, focus groups, and advisory boards. To ensure a balanced nationwide dataset, participation extended across diverse care settings, including the VA National Oncology Program (16%), NCI Centers of Excellence (12%), academic (14%), regional (18%), local community oncology centers (19%), and Federally Qualified Health Centers (21%). Results: The analysis exposed crucial health disparities and communication deficits. Only 49% of patients reported that their provider explained biomarker testing. Conversely, 51% received no such information; importantly, 91% of this uninformed subgroup resided in under-resourced areas. Educational gaps were similarly shown through the collected data: 59% of patients reported lacking an understanding of biomarker utility, with 87% of these individuals receiving care in underserved regions. Additional patient-reported barriers included financial costs (71%), insurance denials or protracted appeals (67%), laboratory processing delays (53%), and operational inefficiencies (38%). After the implementation of targeted biomarker education workshops, engagement metrics improved: inquiries to patient navigators increased by 72%, and 88% of participants affirmed their intent to initiate biomarker testing discussions with their clinicians. Conclusions: At present, substantial socioeconomic and communication barriers restrict the equitable access of precision medicine in gastrointestinal oncology. While financial and systemic obstacles are widespread, this study demonstrates that targeted patient education is the foundation for patient empowerment. To narrow these education gaps, we are expanding the "Test Your Biomarkers" program and integrating dedicated Biomarker Patient Navigators. These actions are essential to provide gastrointestinal cancer patients with the resources needed for shared decision-making, and to eliminate zip-code-dependent variations in cancer care outcomes.

Beyond convolution: Attention-driven vision transformer modeling for breast cancer detection on mammography.

575 Background: Breast cancer is the most commonly diagnosed malignancy among women worldwide, and screening mammography remains central to early detection and mortality reduction. Despite standardized reporting systems, mammographic interpretation is challenged by tissue overlap, subtle lesion morphology, and interobserver variability. Convolutional neural networks (CNNs) have demonstrated strong performance in automated mammography analysis but rely on localized receptive fields that may limit modeling of global spatial relationships critical for detecting architectural distortion and diffuse malignancy. Vision Transformers (ViTs) employ self-attention mechanisms that enable global contextual modeling across entire images. We evaluated the performance of a Vision Transformer for breast cancer classification on mammographic imaging. Methods: We analyzed over 8,000 anonymized mammography images obtained from publicly available Kaggle datasets curated and annotated by expert radiologists. Images included malignant and non-malignant breast findings and were preprocessed and resized to 224×224 pixels. Data were split into training and validation cohorts using stratified sampling at the patient level to prevent data leakage. A Vision Transformer B/16 model pretrained on ImageNet was fine-tuned for binary classification. Images were divided into non-overlapping 16×16 patches, embedded into token sequences with positional encodings and a learnable class token, and processed through 12 transformer blocks with multi-head self-attention. Model performance was evaluated using accuracy, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUROC). Results: The ViT-B/16 model achieved high diagnostic performance, with validation accuracy approaching approximately 96% and AUROC exceeding 0.98. Sensitivity for malignant lesions remained robust across dense and non-dense breast tissue. Attention-based global processing reduced misclassification of lesions with diffuse margins, asymmetric density, and architectural distortion—patterns that are challenging for purely convolutional approaches. Performance was comparable to state-of-the-art CNN models, though achieved with higher parameter count and computational cost. Conclusions: Vision Transformer–based modeling enables accurate breast cancer detection on mammography by capturing global contextual relationships through self-attention. While computationally heavier than optimized CNNs, ViT offers complementary strengths in modeling complex spatial patterns and provides interpretable attention maps aligned with radiologic reasoning. These findings support further evaluation of transformer architectures in large-scale breast cancer screening and diagnostic workflows.

Clinical efficacy of tislelizumab in combination with gemcitabine and nab-paclitaxel and chemoresistance analysis in borderline resectable pancreatic cancer: A prospective pilot study.

2630 Background: Neoadjuvant therapy has been demonstrated to improve the survival outcomes of patients with borderline resectable pancreatic cancer (BRPC). While neoadjuvant therapy is increasingly utilized, exploring novel combination strategies, such as immunotherapy plus chemotherapy, is essential to further enhance surgical resectability and survival outcomes. This study investigated the clinical feasibility of tislelizumab in combination with gemcitabine and nab-paclitaxel for BRPC in a neoadjuvant setting. Methods: In this prospective study, patients diagnosed with BRPC were enrolled. Preoperatively, intravenous injection of tislelizumab (200 mg per time, Q3W) was used for 3 cycles, in combination with gemcitabine (1 000 mg/m 2 , d1, d8) and nab-paclitaxel (125 mg/m 2 , d1, d8). Postoperatively, this regimen continued to be used. The primary endpoints were the margin-negative (R0) resection rate and treatment-related adverse events (TRAEs). Exploratory objectives were resistance to this neoadjuvant regimen. Results: Totally 30 patients were enrolled in this study, among whom 80.0% (24/30) completed neoadjuvant therapy and underwent surgical resection. R0 resection was achieved in 80.0% of the patients (24/30) and in 100.00% of the patients with surgical resection (24/24). Most patients experienced grade I-II TRAEs, and no serious TRAEs occurred. Through the quantitative proteomics and machine learning algorithms for differentially expressed proteins, NT5DC2, FAM3D, CXCL5 and TMT1B were identified to play crucial roles in resistance to the neoadjuvant regimen in pancreatic cancer. Conclusions: Neoadjuvant therapy with tislelizumab plus gemcitabine and nab-paclitaxel demonstrated clinical feasibility and encouraging antitumor activity in BRPC patients, with a favorable safety profile. NT5DC2, FAM3D, CXCL5 and TMT1B may be the biomarkers for preoperative drug resistance in pancreatic cancer. Clinical trial information: ChiCTR2200063680 . Clinical trial information: ChiCTR2200063680 .

Assessment of the role of rapid drug desensitization to treat cancer patient with infusion-related allergic reactions.

11156 Background: Rapid Drug Desensitization (RDD) as The Castells protocol is based on progressively increasing concentrations and infusion rates of the drug under close monitoring, inducing temporary drug tolerance. To assess the role of Rapid Drug Desensitization (RDD) to treat cancer patient with infusion-related allergic reactions (IRRs) we planned an observational trial in 2021. Methods: From 2021 to 2025 all patients experiencing IRRs at the Rimini Oncology Unit, after an allergological evaluation, were treated according to the Castells desensitization protocol. We analyzed the safety of this apporach as well as the treatment discontiunation rate. The IRR severity was classified (grade 1-3) using the Brown classification from 2004. Results: A total of 155 patients were treated with RDD. Among drugs administered using a desensitization protocol, drugs administered with the RDD were paclitaxel (38.06%), oxaliplatin (25.80%), docetaxel (14.10%), and carboplatin (12.9%), irinotecan (1.94%), etoposide (1.94%), liposomal doxorubicin (1.29%), trastuzumab (1.29%), atezolizumab (0.65%), cetuximab (0.65%), cyclophosphamide (0.65%), and cisplatin (0.65%). Grade 3 reactions occurred in 1.29% of patients during RDD, while grade 2 and grade 1 reactions were observed in 3.87% and 2.58%, respectively. No deaths associated with desensitization treatment occurred. The IRRs were managed with treatment interruption and administration of steroids and antihistamines. Notably, 3.22% of patients experienced an allergic reaction during RDD but were able to complete treatment. In total 132 patients completed the planned treatment (85.2%) using the RDD approach. Among those who discontinued, 7 patients (4.5%) stopped due to allergic reactions during the first desensitization cycle. The remaining treatment discontinuations were due to clinical deterioration, patient decision or transfer to another institution (1.9% each), progressive disease (3.9%), or other causes (0.7%). We summarized the characteristics in the table. Conclusions: The RDD protocol is safe and permits to maintain the original schedule in the most part of cancer patients that present a major allergic reaction during chemotherapy. Further trials are probably needed to better define the role of RDD and the drugs primarily candidate to the desensitization protocol. Number of patients % of the total (155 patients) Treatment completed 132 85.2% Discontinuation for infusional reaction 7 4.5% Discontinuation for clinical deterioration 3 1.9% Discontinuation for patient decision 3 1.9% Discontinuation for progressive disease 6 3.9% Discontinuation for transfer to another institution 3 1.9% Discontinuation for other causes 1 0.7%

Integration of molecular subtyping and immune profiling to predict pathologic complete response in HER2+ breast cancer treated with neoadjuvant dual HER2 therapy.

621 Background: Neoadjuvant outcomes are variable in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), highlighting the unmet need for predictive biomarkers. The BluePrint (BP) assay classifies tumors by molecular intrinsic subtype, whereas the ImPrint hormone receptor-positive (HR+) and ImPrint triple-negative genomic signatures predicted immune sensitivity in the ISPY2 trial. Because HER2+ EBCs are genomically heterogeneous, and because anti-HER2 has an immunologic mechanism of action, we hypothesized that BP and ImPrint could be used to predict outcomes (pathologic complete response, pCR) following neoadjuvant chemotherapy + anti-HER2 (trastuzumab + pertuzumab, HP). Methods: We evaluated n=252 HER2+ EBCs receiving neoadjuvant chemotherapy + HP in the prospective, observational FLEX study. Tumors were classified by BP subtype (HER2, Luminal A/B, or Basal) and ImPrint (+ or -). Fisher’s exact test was used to compare pCR rates across BP/ImPrint results. Multivariable logistic regression was used to evaluate independent associations with pCR, adjusting for nodal status and tumor size. Results: 72% of HER2+ EBCs were HR+ and 28% were HR–. In HR+/HER2+ EBC, 52% were classified by BP as non-HER2 (Luminal A 6%, Luminal B 44%, Basal 2%), whereas in HR-/HER2+ EBC, 14% were classified genomically as non-HER2, all of which were Basal. In the HR+/HER2+ subgroup, pCR rates differed significantly by BP subtype and ImPrint, with the highest pCR observed in BP-HER2/ImPrint+ tumors (Table). Similar significant differences were observed in HR-/HER2+ EBC. In a multivariable model of the HR+/HER2+ subgroup, BP and ImPrint independently predicted pCR after controlling for node status and tumor size (BP-HER2 odds ratio/OR: 8.23 [95% CI: 3.47–21.44]; p&lt;0.001; ImPrint+ OR: 4.48 [95% CI: 1.48–14.89]; p&lt;0.05). Conclusions: An integrated genomic approach that combines BP and ImPrint maximizes prediction of pCR outcome in this dataset, particularly for the HR+/HER2+ subgroup. Further evaluation is warranted, as these data could be useful for guiding clinical decision-making, including selection of chemotherapy backbone and adjuvant therapy. Importantly, this approach may help identify patients who are overtreated or undertreated with current strategies, including those with exceptional treatment sensitivity who may be candidates for chemotherapy de-escalation. Clinical trial information: NCT03053193 . pCR rates by genomic subtypes within HR+/HER2– EBC (Fisher’s exact test). Biomarker Subtype* N pCR rate (%) p-value BluePrint HER2 87 55 &lt; 0.001 Luminal B 80 20 ImPrint Positive 30 60 0.006 Negative 151 32 BluePrint + ImPrint HER2, ImPrint+ 14 79 &lt; 0.001 HER2, ImPrint- 73 51 Luminal B, ImPrint+ 14 43 Luminal B, ImPrint- 66 15 *Excluded Luminal A and Basal due to small N.

Prevalence, tumor characteristics, and clinical impact of <i>LZTR1</i> pathogenic variants in a large, pan-cancer cohort.

10621 Background: Heterozygous germline pathogenic/likely pathogenic (P/LP) loss-of-function (LOF) variants in LZTR1 are associated with hereditary schwannomatosis. To date, the prevalence and penetrance remain poorly defined, and there are currently no well-established surveillance guidelines for individuals with incidental LZTR1 P/LP variants. We sought to describe the prevalence of LZTR1 P/LP variants in a large pan-cancer cohort, characterize the tumor genomic profile of patients with these variants, and report the clinical utility of surveillance imaging in asymptomatic carriers diagnosed incidentally. Methods: Patients with germline P/LP variants in LZTR1 were identified from pan-cancer patients who prospectively enrolled in an institutional review board-approved protocol of matched tumor-normal DNA sequencing (MSK-IMPACT). Clinical and tumor characteristics of LZTR1 carriers were collected from electronic medical records. Results: Among 50,537 patients who underwent germline genetic testing via MSK-IMPACT, 157 (0.31%) were found to harbor a heterozygous germline P/LP variant in LZTR1 . Eight patients presented with a schwannoma diagnosis at the time of genetic testing with an additional three reporting a prior history of schwannoma, for a total of 11 (7.01%) meeting criteria for LZTR1-associated schwannomatosis. In the remaining 146 (93%) of patients, the germline LZTR1 P/LP variant was an incidental finding. The most common cancer types in those identified incidentally included prostate (23), breast (22), colorectal (21), sarcoma (14), and uterine (9). Of the 6 schwannomas with tumor data available, all exhibited a second somatic mutation in the NF2 gene, and 5 displayed loss of heterozygosity of the LZTR1 locus in the tumor favoring the mutant allele. LOH data was available for 117 non-schwannoma tumors. Of these, 33 (28.2%) were found to have LOH favoring the mutant LZTR1 allele. Of patients diagnosed incidentally, 29 underwent MRI of the brain and total spine after detection of the LZTR1 P/LP variant for schwannoma screening. An additional 104 patients underwent whole body imaging (PET/CT or CT chest, abdomen, and pelvis) for cancer surveillance. All patients were asymptomatic and did not have clinical evidence of schwannomatosis on history or physical exam. Of these 133 asymptomatic LZTR1 carriers, no (0%) schwannomas were identified. Conclusions: The prevalence of LZTR1 P/LP variants was 0.3% in an unselected pan-cancer population with &lt; 10% meeting criteria for LZTR1 -associated schwannomatosis, suggesting low penetrance. Imaging performed after variant detection did not identify previously unrecognized disease, suggesting limited clinical utility of routine surveillance in asymptomatic carriers without supportive clinical features. These findings support a more selective, risk-informed approach to management of incidental LZTR1 variants.

The effect of adjuvant carboplatin-based chemotherapy in stage I triple-negative breast cancer: A systematic review and meta-analysis of randomized controlled trials.

e12523 Background: Carboplatin has been shown to improve pathologic complete response and disease-free survival (DFS) in patients with stage II-III triple-negative breast cancer (TNBC); however, the role of carboplatin in stage I TNBC is debated. For high-risk stage I TNBC, taxane plus cyclophosphamide (TC)-based regimens +/- anthracyclines are commonly used. We aimed to assess the impact of adjuvant carboplatin-based regimens on DFS in stage I TNBC. Methods: We performed a systematic search of PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published upto January 2026 comparing adjuvant carboplatin-based versus non-carboplatin-based chemotherapy in stage I-III TNBC. Trials which included DFS by pT1 or stage I subgrouping were eligible for inclusion. The primary outcome was DFS in the pT1 or stage I group; secondary outcomes were DFS in the pT2+ or stage II/III group and adverse events (AEs) in all patients. Meta-analysis was conducted using a random-effects model in R version 4.5.2. Heterogeneity was assessed with I² statistics. Results: Five RCTs with 2,692 patients were included, of which 1,261 (46.8%) had pT1 disease. Among these, 643 (51%) received adjuvant carboplatin-based regimens, compared to 618 (49%) who received non-carboplatin-based regimens. Carboplatin-based regimens improved DFS in pT1 (stage I) disease compared to non-carboplatin-based regimens (HR 0.62; 95% CI 0.44-0.85; P = 0.003). DFS was also improved with carboplatin-based regimens in patients with pT2+ disease (stage II/III) (HR 0.70; 95% CI 0.53-0.93; P = 0.014) and in the overall population (HR 0.63, 95% CI 0.51-0.78, P &lt; 0.001) compared to non-carboplatin-based regimens. No significant differences were observed between carboplatin-based and non-carboplatin based regimens for either all-grade (RR 1.04, 95% CI 0.98-1.10, P = 0.154) or grade 3/4 (RR 1.04, 95% CI 0.72-1.50, P = 0.834) hematologic and non-hematologic AEs. Conclusions: Adjuvant carboplatin-based chemotherapy improves DFS compared to non-carboplatin-based chemotherapy in early-stage TNBC, including in patients with pT1 disease, without a corresponding increase in toxicity. These findings support consideration of carboplatin in the adjuvant treatment regimen in patients with high-risk stage I TNBC.

A phase 1, first-in-human study of DS3610, a stimulator of interferon genes (STING) agonist antibody-drug conjugate (ADC), in patients with advanced/metastatic solid tumors.

TPS3159 Background: While immunotherapies have improved treatment for patients with advanced/metastatic solid tumors, there remains a need for novel therapies that can overcome resistance to existing therapies, enhance antitumor activity, and delay disease progression. Promoting the innate immune response through activation of the endoplasmic reticulum adaptor protein stimulator of interferon genes (STING) has been associated with antitumor activity. DS3610 is an antibody–drug conjugate (ADC) comprising an anti-epidermal growth factor receptor (EGFR) monoclonal antibody attached to an immunomodulatory payload that acts as an agonist of STING. EGFR is a transmembrane receptor tyrosine kinase that is overexpressed in a broad range of solid tumors. DS3610 is designed to deliver the STING agonist payload directly to the tumor microenvironment, activating immune cells such as antigen-presenting cells and T cells, and inducing immune targeting of cancer cells. The antibody component has novel Fc modifications designed to reduce the risk of class-specific adverse events, such as systemic cytokine release. Methods: DS3610-071 (NCT07159126) is a Phase 1, first-in-human, open-label, global, dose-escalation study of DS3610 (N≈70). Patients must be adults with advanced or metastatic solid tumors and be intolerant to standard-of-care therapies or have disease that has relapsed after or is refractory to such therapies. Eligible tumor types include non-small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial carcinoma, colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer, biliary tract cancer, and uterine cancer. Patients must have measurable disease per RECIST 1.1; an ECOG performance status of 0, 1, or 2; and be willing and able to provide a pretreatment or archival tumor tissue sample. Patients will receive DS3610 at escalating doses. The primary objectives are to assess the safety and tolerability of DS3610 and to determine the recommended dose(s) for expansion for further evaluation of DS3610. Safety endpoints include identifying dose-limiting toxicities and treatment-emergent adverse events. Secondary endpoints include the assessment of DS3610 immunogenicity, based on the prevalence and incidence of antidrug antibodies, and the evaluation of DS3610 pharmacokinetics. Exploratory endpoints include evaluating the efficacy of DS3610 and identifying biomarkers that may be associated with clinical benefit. Enrollment is ongoing. Clinical trial information: NCT07159126 .

A phase 2 study of plinabulin (Plin)/docetaxel (Doc) plus pembrolizumab (Pemb) in metastatic NSCLC (mNSCLC) after acquired resistance (AR) to anti–PD-1/L1 alone or in chemotherapy combination: Efficacy and immunophenotyping.

8567 Background: PD-1/L1 inhibitors have become a part of 1L treatment for EGFR/ALK wild-type NSCLC. However, &gt;60% patients (pts) develop AR associated with T cell exhaustion and defective antigen presentation. Doc remains a mainstay for pts who relapse after anti-PD-1/L1 therapy, while multiple late-stage clinical trials have failed in comparison. Plin is a first-in-class, brain-penetrating dendritic cell maturation agent with clinically validated potential to restore antigen presentation/T cell function after AR to PD-1/L1 inhibitors. Plin also reduces severe neutropenia and thereby increases Doc tolerability. In a global phase 3 study (Dublin-3, n=559), Plin/Doc outperformed Doc with significant OS/PFS/ORR benefits, doubling of 2-/3-year OS rates, and 80% reduction in G4 neutropenia (p&lt;0.0001). The aim of this study was to assess the efficacy/safety of Plin/Doc plus Pemb in mNSCLC after anti-PD-1/L1 based therapy. Methods: This single-arm phase 2 trial (NCT05599789; Study 303) enrolled 47 pts after immediate progression on anti-PD-1/L1 alone or combined with platinum doublets. Pts received Plin 30mg/m2, Doc 75mg/m2 and Pemb 200mg, on Day 1 in 21-day cycles. The primary/secondary endpoints at the median follow-up of 20.6 months (mo) are tabulated. For immunophenotyping, whole blood from baseline and post treatment were analyzed by flow cytometry. Results: At the data cutoff date of 31-Dec-2025, cORR was 18.2% with 79.5% DCR. mPFS was 7.0 mo, and mDoR at 9.3 mo. While mOS was 34 mo, the 24-mo OS rates were 64.3% (ITT), 71.1% (NSQ), and 52.0% (SQ). In all endpoints assessed, prior Pemb exposure did not reduce the efficacy of this regimen. Whole blood analysis indicated that activated CD4+/CD8+ T cells and proliferating Ki67+CD8 T cells were significantly increased post two cycles of treatment. Also observed were concurrent elevations of Ki67+B cells and CD38+NK cells. Conclusions: Plin/doc plus Pemb shows promising efficacy in mNSCLC with AR to anti-PD-1/L1 confirmed by immune activation post-treatment. TRAEs were manageable. These findings along with DUBLIN-3 support a global confirmatory study in EGFR/ALK wild-type NSQ NSCLC following progression on anti-PD1/L1 based therapy. Clinical trial information: NCT05599789 . Efficacy endpoints. Endpoint* ITT(N=47) NSQ(N=30) SQ(N=17) Primary endpoint cORR (RECIST 1.1) 18.2% 13.8% 26.7% Secondary endpoints mPFS (RECIST 1.1) 7.0 mo 7.7 mo 5.5 mo mOS 34 mo (not reached) 34 mo mDoR (RECIST 1.1) 9.3 mo (not reached) 9.1 mo DCR (PR+SD &gt; 4 mo) 79.5% 82.8% 73.3% 12-mo OS rate 78.2% 80.0% 74.8% 24-mo OS rate 64.3% 71.1% 52.0% *cORR/DoR/DCR: 44 evaluable pts; PFS/OS &amp; follow-up duration: ITT.

Effect of melatonin on the fatigue, sleep, and depression symptom cluster in breast cancer according to dosage and treatment phase: A systematic review and meta-analysis.

e24112 Background: Patients with breast cancer (BC) frequently experience a debilitating symptom cluster of sleep disturbances, depression, and fatigue, significantly impairing quality of life. While melatonin is a common supportive therapy, clinical trials yield conflicting results due to heterogeneous protocols. This meta-analysis clarifies melatonin’s efficacy by evaluating the pharmacological threshold (High-dose: ≥10mg vs. Low-dose: &lt; 10mg) and clinical treatment phase (Active Treatment vs. Post-Treatment). Methods: Following PRISMA guidelines, a systematic search of PubMed, Embase, and Cochrane identified eight RCTs comparing oral melatonin to placebo in BC patients. Outcomes were sleep quality, depression, and fatigue, measured via Standardized Mean Difference (SMD). Data were pooled using random-effects models. Pre-specified subgroup analyses investigated dosage (≥10mg vs. &lt; 10mg) and treatment phase (Active vs. Post-Treatment). Heterogeneity was assessed using the I 2 statistic and Cochrane Q test to ensure statistical rigor. Results: Eight RCTs involving 675 unique patients were included. For depression, a significant dose-dependent benefit was identified; high-dose melatonin (≥10mg) significantly reduced symptoms (SMD -1.07; 95% CI -1.43 to -0.71; P &lt; 0.00001; I 2 = 0%), whereas low-dose ( &lt; 10mg) had no significant effect (P = 0.83). For fatigue, a robust benefit was observed specifically during radiotherapy (SMD -1.33; 95% CI -1.82 to -0.84; P &lt; 0.00001), while non-radiotherapy fatigue showed no significant improvement (SMD 0.14; P = 0.20; I 2 = 0%). Sleep quality improved significantly during active treatment in high-dose groups (SMD -1.75; 95% CI -2.54 to -0.97; P &lt; 0.0001), though overall sleep results were confounded by extreme heterogeneity (I 2 = 98%) in post-treatment low-dose settings. Conclusions: Melatonin’s therapeutic benefit in BC is strictly dose-dependent and phase-specific. High-dose supplementation (≥10mg) is a robust co-adjuvant for managing depression and treatment-related distress during active chemotherapy and radiotherapy, offering a high-safety-profile intervention. Conversely, low-dose melatonin is ineffective for chronic survivorship symptoms. These findings advocate for implementing standardized high-dose protocols in supportive oncology during active adjuvant therapy to optimize patient-reported outcomes.

Baseline predictors of early mortality in patients with PD-L1–high advanced NSCLC treated with first-line immunotherapy.

e20691 Background: Single-agent immunotherapy (IT) is the standard first-line treatment for patients (pts) with advanced non–small cell lung cancer (aNSCLC) and PD-L1 ≥50%. Its favorable tolerability may increase use in frail pts or near the end of life. Identifying baseline features associated with lack of benefit is therefore crucial. Methods: We retrospectively analyzed pts with aNSCLC and PD-L1 ≥50% treated with first-line single-agent IT at Modena University Hospital (June 2020–February 2025). Data cut-off was June 30, 2025. Early mortality (EM) was defined as death within 3 months from treatment initiation. Group comparisons used logistic regression or Fisher’s exact test, as appropriate. Overall survival (OS) was estimated by Kaplan–Meier. Results: Fifty-four pts were included; 13 (24%) experienced EM, including 5 pts (9%) who died within the first month. 12 of 13 pts (92.3%) in the EM group received IT within the last 30 days of life. EM was significantly associated with poor performance status (PS) ≥2 (69% vs 34%; Odds Ratio (OR) 4.34, 95% CI 1.10–17.16; p = 0.032), and with ≥2 comorbidities (69% vs 37%; OR 3.90, 95% CI 0.99–15.35; p = 0.046). Never-smoking status was observed exclusively in the EM group (23% vs 0%; p = 0.022). Hospitalization at diagnosis (62% vs 49%) and baseline steroid use (62% vs 44%) were numerically higher in EM pts, without reaching statistical significance. EM was more frequent in pts with bone (85% vs 24%; OR 17.05, 95% CI 3.09–93.93; p = 0.001) and liver metastases (39% vs 12%; OR 4.50, 95% CI 1.01–20.01; p = 0.043), whereas the presence of ≥2 disease-related symptoms was not associated with EM. EM was also associated with poor Lung Immune Prognostic Index (LIPI) score (77% vs 32%; OR 7.31, 95% CI 1.32–40.59; p = 0.020) and higher Palliative Prognostic (PaP) score (mean 6.23 vs 3.71; p = 0.016). Age, sex, BMI, and PD-L1 expression level were not associated with EM. In the overall population, ECOG ≥2 and PaP score were significant predictors of OS. Median OS was 6.0 vs 23.2 months (ECOG ≥2 vs &lt; 2; p = 0.003) and 4.8 vs 20.8 months (PaP B+C vs A; p = 0.003). Conclusions: In pts with aNSCLC and PD-L1 ≥50%, EM following initiation of first-line single-agent IT is not uncommon and may be driven by identifiable baseline clinical and prognostic factors. Poor PS, multiple comorbidities, selected metastatic patterns, and validated prognostic scores such as LIPI and PaP were statistically associated, in this study, with a high risk of EM. Reassessment of these readily available prognostic tools may improve patient selection, help avoid futile treatment, limit unnecessary toxicity and resource utilization, and reduce financial toxicity at the end of life. Prospective studies with larger cohorts are warranted to further refine selection strategies and preserve quality of life.

Effect of transanal vs. laparoscopic total mesorectal excision on 5-year overall survival in patients with rectal cancer: The TaLaR trial.

3631 Background: Transanal total mesorectal excision (taTME) has emerged as a widely adopted surgical approach for rectal cancer. Prior studies have reported favorable short-term outcomes, histopathological quality, and complication profiles for taTME compared with laparoscopic total mesorectal excision (laTME). However, the long-term oncologic effectiveness of taTME remains debated. In our previous work, we demonstrated that 3-year disease-free survival after taTME was noninferior to that after laTME among patients with mid-to-low rectal cancer. Building on these findings, the present study aimed to report the 5-year overall survival (OS) between taTME and laTME. Methods: We conducted a phase 3, randomized, open-label, noninferiority trial to compare the survival outcomes of taTME versus laTME in patients with rectal cancer located below the peritoneal reflection. This trial encompassed 16 hospitals across 10 provinces in China, with a total enrollment of 1,115 patients. We set the 3-year disease-free survival (DFS) and 5-year overall survival (OS) as the primary endpoints for analysis. This analysis of the 5-year overall survival was conducted following a predefined modified intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT02966483. Results: As of June 2025, the overall 5-year overall survival (OS) rate was 83.60%, comprising 86.06% in the transanal TME (taTME) group and 81.24% in the laparoscopic TME (laTME) group. The overall 5-year disease-free survival (DFS) rate was 75.90%, with DFS rates of 77.65% in the taTME group and 74.18% in the laTME group. Conclusions: Based on preliminary results from a five-year follow-up, taTME is expected to achieve a five-year overall survival (OS) that is non-inferior to laTME. Our findings will support the routine use of taTME in mid-to-low rectal cancer, particularly in men, obese individuals, and those who have received neoadjuvant therapy. Clinical trial information: NCT02966483 . 5-year survival results between the laTME group and the taTME group. laTME taTME HR 5-year OS（97.5% CI） 81.24% (77.82%-84.82%) 86.06%(83.04%-89.20%) 0.73 (0.54-1.10) 5-year DFS（95% CI） 74.18%(70.45%-78.10%) 77.65%(74.15%-81.32%) 0.86(0.68-1.11)