ABSTRACT Background Effective treatment options remain limited for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), including patients who have progressed after platinum‐based chemotherapy and systemic‐therapy‐naïve patients. This Phase Ib trial evaluates the efficacy and safety of finotonlimab, a PD‐1 antibody, combined with SCT200, an EGFR antibody. Methods This prospective, multicenter, open‐label study enrolled patients into two cohorts: Cohort A (previously treated with platinum‐based chemotherapy and immune checkpoint inhibitors) and Cohort B (systemic therapy‐naïve). Patients received finotonlimab (200 mg every 3 weeks) and SCT200 (6 mg/kg weekly for 12 weeks, then 8 mg/kg every 2 weeks). The primary endpoint was objective response rate (ORR). Results Among 41 patients, Cohort A (n = 11) showed an ORR of 27.3%, median progression‐free survival (PFS) of 5.8 months, and median overall survival (OS) of 10.6 months. Cohort B (n = 30) had an ORR of 56.7%, median PFS of 9.6 months, and an estimated median OS of 13.6 months. Common treatment‐related adverse events included hypomagnesemia (63.4%), rash (41.5%), and acneiform dermatitis (36.6%), which were manageable. Conclusions The combination of finotonlimab and SCT200 demonstrates promising efficacy, particularly in systemic therapy‐naïve patients, warranting further investigation. Trial Registration ClinicalTrials.gov identifier: NCT05552807; Chinadrugtrials.org.cn identifier: CTR20220917

Lucitanib is a novel multi-target inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-3, and platelet-derived growth factor receptor α/β. This open-label, multicenter, single-arm Phase II study evaluated lucitanib plus the anti-programmed cell death 1 (PD-1) antibody toripalimab in patients with advanced solid tumors refractory to standard therapies. Patients received lucitanib (10 mg) once daily plus toripalimab (240 mg) every 3 weeks until progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) and secondary endpoints included disease control rate, duration of response, progression-free survival (PFS), overall survival, and safety. Among 131 patients across four cohorts (PD-1-treated recurrent/metastatic nasopharyngeal carcinoma [NPC], PD-1-naïve NPC, recurrent/metastatic endometrial cancer [EC], and other tumors), ORR was 34.1%, 45.8%, 38.5%, and 13.5%, respectively. Median PFS was 4.2 months (95% confidence interval [CI], 4.1-5.6), 6.5 months (95% CI, 4.0-not estimable [NE]), 5.6 months (95% CI, 2.78-11.21), and 9.7 months (95% CI, 5.4-NE). The most common Grade ≥ 3 treatment-related adverse events were hypertension (37.4%), proteinuria (10.7%), and thrombocytopenia (10.7%). Lucitanib plus toripalimab showed encouraging antitumor activity with manageable safety in heavily pretreated advanced solid tumors, supporting further randomized evaluation, particularly in NPC and EC. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2400087935.

Glioblastoma (GBM) is highly heterogeneous, complicating effective tumor elimination. Among GBM subtypes, the mesenchymal (MES) variant is associated with the poorest prognosis. Notably, macrophage infiltration is significantly higher in MES GBM. However, the regulatory networks underlying this distinct MES GBM microenvironment remain poorly understood. Here, we demonstrate that MES glioblastoma stem cells (GSCs) exhibit a preferential expression and secretion of the protein LY96. Mechanistically, MES GSCs engage an autocrine LY96-TNFRSF1B signaling axis that activates NF-κB, thereby promoting their proliferation, self-renewal, and maintenance of the MES state. Inhibition of LY96 in vivo suppresses GBM growth and prolongs survival in animal models. Additionally, LY96 acts in a paracrine manner on tumor-associated macrophages (TAMs), driving their polarization toward a MES-like state. Collectively, our findings identify LY96 as a key regulator of the MES state in GSCs and a driver of MES-like polarization in TAMs. Therapeutic strategies targeting LY96 and its downstream effectors may improve GBM treatment outcomes.

TPS7106 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Aberrant activation of the Bruton's tyrosine kinase (BTK)-related signaling pathway is present in the non-GCB subtype of DLBCL (Davis et al. Nature 2010). Multiple BTK inhibitors (BTKi) have demonstrated efficacy in relapsed or refractory (R/R) non-GCB DLBCL (Strati et al. Haematologica. 2021; Wilson et al. Nat Med. 2015; Yang et al. Blood Adv. 2022), however, there remains room for further improvement. Rocbrutinib is a novel, highly selective, the fourth generation covalent (irreversible) and non-covalent (reversible) BTKi. Phase 1 study showed that in 45 patients with R/R non-GCB DLBCL who had received ≥2 prior lines of systemic therapy, rocbrutinib monotherapy achieved an overall response rate (ORR) of 57.8% and a complete response (CR) rate of 31.3%( Song et al. CSCO. 2025). This article describes the design and progress of a phase 2 pivotal study aimed at comparing the efficacy and safety of rocbrutinib versus investigator's choice of therapy in patients with R/R non-GCB DLBCL. Methods: ROCK-2 (NCT07189065; CTR20253693) is an open-label, randomized, multicenter phase 2 study conducted in China. Eligible patients must have non-GCB DLBCL, not otherwise specified (NOS) per the 2017 WHO classification, received ≥2 prior lines of systemic therapy. Additionally, patients must have measurable disease, an ECOG performance status of 0-2, and adequate hematologic and organ function. Key exclusion criteria include central nervous system involvement, DLBCL transformed from indolent lymphoma, prior refractoriness to BTK-targeting agents, uncontrolled systemic diseases, active infection. Approximately 150 eligible subjects will be randomized 1:1 to receive either rocbrutinib or BR/R 2 , stratified by the number of prior lines of therapy (2 vs ≥3) and International Prognostic Index (IPI) score (0-2 vs 3-5). Subjects in the experimental group will receive rocbrutinib [200 mg once daily (QD)] until disease progression or unacceptable toxicity. Subjects in the control group will receive either BR or R 2 according to the investigator's choice. The BR regimen consists 6 cycles of rituximab (375 mg/m² on day 1) plus bendamustine (90 mg/m²/d on days 1-2). The R 2 regimen consists of rituximab (375 mg/m² on day 1 of cycles 1-6) plus lenalidomide (20 mg QD on days 1-21 of each 28d-cycle until disease progression or unacceptable toxicity). The primary endpoint is ORR assessed by Independent Review Committee (IRC) according to the 2014 Lugano criteria. Secondary endpoints include ORR assessed by investigator (INV), and CR rate, progression-free survival (PFS), duration of response (DOR), time to response (TTR), overall survival (OS) assessed by IRC or INV. The first subject was enrolled on Nov 27 th ,2025. Recruitment is ongoing. Clinical trial information: NCT07189065 .

Introduction: China bears the highest global burden of esophageal cancer (EC), with smoking, high alcohol use, a diet low in vegetables, and tobacco chewing as established risk factors. However, the specific impact on EC-related mortality and disability-adjusted life years (DALYs) in China remains unclear. This study aimed to use the Global Burden of Disease Study (GBD) 2023 to analyze trends in the attributable burden of EC from 1990 to 2023 and to project the burden of disease through 2040 to inform targeted prevention strategies. Methods: In this study, the effects of four risk factors (smoking, high alcohol use, diet low in vegetables, and chewing tobacco) on mortality and DALYs of EC in China were calculated based on the GBD 2023 data, stratified by sex and age. A Joinpoint regression model was used to assess trend changes from 1990 to 2023, and a Bayesian Age-Period-Cohort model was used to predict trend changes up to 2040. Results: Between 1990 and 2023, the age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years for the four major risk factors showed an overall decreasing trend, with diets low in vegetables showing the largest decrease. In 2023, smoking was the leading cause of EC deaths in China (65.21%), followed by high alcohol use (29.11%). The burden of EC was significantly higher in males than in females. The age distribution shows that men aged 50–70 years have the highest attributable burden, whereas the peak for females is relatively delayed. Projections indicate that by 2040, the ASMR for the four major modifiable risk factors of EC shows a declining trend. Conclusions: Although the burden of EC in China is decreasing, smoking and high alcohol use remain major risk factors, particularly among male individuals and those in the middle-aged and elderly demographic. To further reduce the disease burden, it is necessary to enhance tobacco and alcohol control, optimize endoscopic screening for high-risk populations, and integrate early detection programs into healthcare policies, while promoting dietary modifications.

ABSTRACT Background ALK‐positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare subtype of peripheral T‐cell lymphoma with traditionally favorable prognosis. The introduction of brentuximab vedotin (BV) has significantly impacted treatment outcomes, but the long‐term survival trends and predictive factors for this population remain underexplored. Methods A total of 1548 patients diagnosed with ALK+ ALCL between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into two eras: pre–BV (2004–2010, n = 795) and post–BV (2011–2017, n = 753). Overall survival (OS) was compared between eras. A random survival forest (RSF) model was constructed to identify prognostic factors and stratify survival risk in the post–BV cohort. Results OS significantly improved in the post–BV era (HR = 0.68, 95% CI: 0.58–0.81, p < 0.001), with the 5‐year OS increasing from 59.3% to 72.3%. The RSF model identified age, Ann Arbor stage, primary site, B symptoms, and radiotherapy as key prognostic factors, showing good discrimination with C‐indices of 0.775 (training cohort) and 0.728 (testing cohort). Notably, radiotherapy was found to be a protective factor. The model effectively stratified patients into high‐risk (5‐year OS: 49.3%) and low‐risk (86.0%) groups. Conclusion The introduction of BV has significantly improved real‐world survival in ALK+ ALCL. The RSF model enables individualized risk stratification and may support future precision treatment strategies.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with stage at diagnosis significantly influencing survival outcomes. This systematic review evaluates global variations in lung cancer stage distribution at diagnosis and examines the associations of socioeconomic factors and screening programs with these disparities. We conducted a systematic review following PRISMA guidelines, searching PubMed, Embase, and grey literature up to August 14, 2024, to identify population- or hospital-based cancer registry data on lung cancer staging. Data from 36 countries were analyzed, focusing on the proportion of distant metastatic cases. We assessed associations with Human Development Index (HDI) and Socio-Demographic Index (SDI) using case-number-weighted linear regression model and evaluated time trends in countries with and without screening programs. Subgroup analyses explored variations by sex, age, and tumor type. Among the 35 countries analyzed in the main study, the median proportion of lung cancer cases diagnosed with distant metastasis was 50.8

ObjectivesOur goal was to evaluate the influence of the interlude between neoadjuvant immunochemotherapy (NAIC) and surgery on both pathologic responses and surgical outcomes in head and neck squamous cell carcinoma (HNSCC).MethodsPatients undergoing surgery for HNSCC following NAIC were retrospectively enrolled and determined based on the time to surgery (TTS). Impact of TTS on major pathologic response (mPR), pathologic complete response (pCR), surgical complication and 3-year disease free survival (DFS) was evaluated.ResultsA total of 356 patients were enrolled. 225 patients (63.2%) achieved a mPR, among whom a pCR was achieved in 104 patients (29.2%). When compared to the TTS<1 week group, patients with a TTS of 1-2 weeks and those with a TTS of 2-3 weeks exhibited comparable rates of pCR and mPR achievement; however, patients who underwent surgery more than 3 weeks after the completion of NAIC had a significantly reduced likelihood of achieving total tumor regression by 16% (95% CI: 1%-23%) and lower probability of major tumor regression by 21% (95% CI: 5%-36%). The TTS >3 weeks group bore an additional 0.67-fold risk of experiencing surgical complications and 1.23-fold increased risk of adverse recurrence or death events compared to TTS <1 cohort.ConclusionA TTS exceeding 3 weeks was independently associated with a diminished likelihood of achieving both pCR and mPR, an increased rate of surgical complications, and a shorter duration of DFS. These findings suggest that the interval between surgery and the completion of NAIC may be optimal when kept within 3 weeks in HNSCC, though this warrants prospective validation.

Supplementary Methods, Supplementary Tables S1-6, Supplementary Figure S1

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive malignancies with poor prognosis and limited response to standard chemotherapy. Although recent advances in molecular and biological characterization have refined PTCL classification, profound molecular heterogeneity continues to result in highly variable treatment outcomes. Emerging targeted and immunotherapeutic agents show activity in specific subtypes, yet responses remain difficult to predict amid their biological complexity. This review synthesizes current molecular insights, evaluates the limitations of existing therapies, and explores the potential of multi-omics profiling integrated with artificial intelligence (AI) to decode complex signatures for improved subtype classification, treatment response prediction, and survival prognostication. By addressing the "black-box" issue through explainable AI, this approach offers a promising framework to advance PTCL management from empirical treatment toward biomarker-driven precision therapy.

PURPOSE:This multicenter, phase IIa trial (NCT04868162) investigated the efficacy and safety of becotatug vedotin, an anti-epidermal growth factor receptor (EGFR) antibody-drug conjugate, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who have limited therapeutic options. PATIENTS AND METHODS:Patients with R/M SCCHN who progressed after platinum-based chemotherapy and/or programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, including those with multiple lines of prior therapy, were administered intravenous becotatug vedotin at either 2 or 2.3 mg/kg every 3 weeks. The primary endpoint was the objective response rate (ORR). RESULTS:Sixty-seven patients were enrolled (35 received 2 mg/kg and 32 received 2.3 mg/kg). The ORR was 20.9% [14/67, 95% confidence interval (CI), 11.9-32.6], with a median duration of response (DoR) of 10.9 months (95% CI, 2.6-15.1). The median progression-free survival (PFS) was 2.9 months (95% CI, 1.8-3.9), and the median overall survival (OS) was 6.7 months (95% CI, 5-8.9). Treatment-related adverse events (TRAE) were reported in 91% (61/67) patients, most commonly being rash (26.9%), pruritus (25.4%), constipation (23.9%), and anemia (20.9%). CONCLUSIONS:Becotatug vedotin demonstrated promising antitumor activity with a manageable safety profile in previously heavily treated R/M SCCHN, particularly at the recommended dose of 2.3 mg/kg, among patients who had failed platinum-based chemotherapy and PD-1/PD-L1 inhibitors (≤2 prior lines of therapy).

Traditional American Joint Committee on Cancer (AJCC) staging exhibits critical limitations when assessing oral squamous cell carcinoma (OSCC) treated with neoadjuvant immunochemotherapy (NICT). This study proposed using the percentage of residual viable tumor (

Optimal management of the clinically node-negative (cN0) neck in early-stage (cT1-2) lip squamous cell carcinoma (SCC) remains controversial. Sentinel lymph node biopsy (SLNB) offers a minimally invasive staging alternative to observation or elective neck dissection, but its diagnostic accuracy, lymphatic mapping patterns, and survival impact in lip SCC are not well-established. We conducted a retrospective study of 101 patients with cT1-2N0 lip SCC treated at a tertiary cancer center (2005–2022), comparing SLNB-guided management (n = 46) to observation (n = 55). Diagnostic performance of SLNB was evaluated against final histopathology. Lymphatic mapping was performed using lymphoscintigraphy/SPECT and gamma probe. Survival outcomes were analyzed using Kaplan–Meier and Cox regression, with sensitivity analysis using inverse probability of treatment weighting (IPTW). SLNB achieved a 100

Abstract In the phase 3 STARGLO trial, glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) demonstrated superior overall survival (OS) vs rituximab plus GemOx (R-GemOx), in patients with autologous stem cell transplant (ASCT)–ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We present efficacy and safety from STARGLO, with 3 years of follow-up, including in clinically relevant subgroups. After a median OS follow-up of 35.1 months (data cutoff: 1 May 2025), Glofit-GemOx continued to demonstrate favorable outcomes vs R-GemOx, respectively: median OS, 25.5 vs 12.5 months (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.4-0.8); median progression-free survival, 14.4 vs 3.3 months (HR, 0.41; 95% CI, 0.3-0.6); complete response rate, 58.5% vs 25.3%. Glofit-GemOx was particularly efficacious in the second-line (2L) vs third-line or later setting (3-year OS rate, 54.6% [95% CI, 45.2-64.0] vs 33.2% [95% CI, 21.2-45.3]). In the 2L setting, among patients with primary refractory disease or early treatment failure, the 36-month OS rate was 46.1% (95% CI, 35.2-56.9) with Glofit-GemOx vs 16.5% (95% CI, 3.4-29.6) with R-GemOx. Glofit-GemOx was favorable over R-GemOx regardless of patient age, with consistent efficacy observed across age categories, including in older patients (aged ≥75 years). No new safety signals were identified. With extended follow-up, fixed-duration Glofit-GemOx continues to demonstrate superior survival vs R-GemOx in ASCT-ineligible patients with R/R DLBCL, with favorable outcomes pronounced in the 2L setting, and consistent across subgroups including older patients and those with early relapsing disease. These data support Glofit-GemOx as an effective off-the-shelf treatment with curative potential in R/R DLBCL. This trial was registered at www.clinicaltrials.gov as NCT04408638.

BackgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with lymph node metastasis (LNM) significantly influencing prognosis. PTC cases were categorized based on the presence or absence of coexisting thyroiditis: those with thyroiditis were designated as PTC-thyroiditis, and those without as PTC-blank. Although both subtypes exhibit distinct clinical and genomic profiles, the mechanisms underlying LNM—particularly the role of extracellular matrix (ECM) remodeling and cancer-associated fibroblasts (CAFs)—remain poorly understood. This study aimed to compare the molecular and cellular heterogeneity of PTC-blank and PTC-thyroiditis, identify key drivers of LNM, and develop a predictive model for clinical use.MethodsWe integrated bulk RNA-seq data from the TCGA database and single-cell RNA-seq (scRNA-seq) data from GSE184362 to analyze clinical, genomic, and tumor microenvironment (TME) differences between PTC-blank and PTC-thyroiditis. Differential expression analysis, Gene Set Enrichment Analysis (GSEA), and immune cell infiltration analysis were performed. Fibroblast subpopulations were characterized at single-cell resolution. Machine learning algorithms (LASSO, random forest, KNN) were applied to identify LNM-related genes and construct a predictive model. Mendelian randomization (MR) and molecular docking were used to validate causal genes and potential drug interactions.ResultsPTC-blank exhibited higher T, N, and M stages and increased mutations in BRAF and MUC16 compared to PTC-thyroiditis. LNM in PTC-blank was associated with ECM remodeling and collagen fiber accumulation, associated with a distinct PI16+ fibroblast subcluster with active ECM organization functions. In contrast, LNM in PTC-thyroiditis involved immune-related pathways without significant fibroblast infiltration or ECM changes. A 17-gene predictive model for LNM was developed, with the KNN classifier demonstrating high accuracy. MR analysis identified SHISA5 as a causal risk gene for thyroid cancer, and molecular docking revealed strong binding affinity with acetaminophen, suggesting therapeutic potential.ConclusionsPTC-blank and PTC-thyroiditis exhibit distinct LNM mechanisms: ECM remodeling and fibroblast infiltration are associated with metastasis in PTC-blank, while immune dysregulation appears to be more prominent in PTC-thyroiditis. The identified 17-gene model offers robust predictive value for LNM risk, and SHISA5 represents a novel causal gene and potential therapeutic target. These findings provide insights into subtype-specific management strategies for PTC patients.

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is a common form of esophageal cancer with a poor prognosis and limited treatment options. Epidermal growth factor receptor (EGFR), an overexpressed oncogenic gene in all ESCC patients, is an attractive target for developing therapies against ESCC. There is an extremely urgent need to develop immunotherapy tools targeting EGFR for the treatment of ESCC. Methods: In this study, we developed human Interleukin-21 (hIL-21)-armed, chimeric-antigen-receptor-modified T (CAR-T) cells targeting EGFR as a new therapeutic approach. The CAR contains a variable domain of the llama heavy chain of heavy-chain antibodies (VHHs), also known as nanobodies (Nbs), as a promising substitute for the commonly used single-chain variable fragment (ScFv) for CAR-T development. Results: We show that nanobody-derived, EGFR-targeting CAR-T cells specifically kill EGFR-positive esophageal cancer cells in vitro and in animal models. Human IL-21 expression in CAR-T cells further improved their expansion and antitumor ability and were observed to secrete more interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and Interleukin-2 (IL-2) when co-cultured with ESCC cell lines in vitro. More CD8+ CAR-T cells and CD3+CD8+CD45RO+CD62L+ central memory T cells were detected in CAR-T cells expressing hIL-21 cells. Notably, hIL-21-expressing CAR-T cells showed superior antitumor activity in vivo in a KYSE-150 xenograft mouse model. Conclusions: Our results show that hIL-21-armed, nanobody-derived, EGFR-specific CAR-T cell therapy is a highly promising option for treating ESCC patients.