This article reports a case of a patient with small primary foci (11 mm*8 mm), highly malignant ROS1 fusion-positive non-small cell lung cancer (NSCLC) with mediastinal and supraclavicular lymph node metastases. After neoadjuvant crizotinib targeted therapy, the patient underwent lobectomy and lymph node dissection. Postoperatively, continuous targeted therapy combined with Traditional Chinese Medicine (TCM) adjuvant intervention achieved an extremely prolonged 62-month progression-free survival (PFS) without drug resistance or obvious side effects, compared to the median real-world PFS (rwPFS) of approximately 20 months for guideline-recommended crizotinib treatment. The last follow-up in August 2025 showed the patient remained in good survival status. This case highlights a novel strategy of neoadjuvant targeted downstaging followed by surgical resection for small-lesion, highly invasive NSCLC, as well as the potential value of integrating postoperative Chinese-Western medicine management for long-term survival and treatment tolerance.

Antigen-escape and on-target off-tumor effects limit the application of chimeric antigen receptor (CAR)-T cells in solid tumors. Glypican-3 (GPC3) and hepatitis B virus (HBV) are two emerging therapeutic targets for CAR-T cell therapy in hepatocellular carcinoma (HCC). In this study, we generated single-antigen CARs against HBV surface antigen (HBsAg) and GPC3. HBsAg-CAR-T specifically targeted HBV-positive HCC cells, showing superior antitumor activity compared to GPC3-CAR-T. However, concerns arose about off-tumor liver cytolysis by HBsAg-CAR-T due to the membrane localization of HBsAg in non-malignant liver cells. Moreover, HBsAg and GPC3 were heterogeneously expressed in approximately 27 percent of tested patients with HCC. To address these challenges, we developed bicistronic HBsAg-GPC3-CAR-T cells that selectively recognized double-positive HCC cells, thereby reducing off-tumor toxicity. Co-administration of HBsAg-CAR-T and GPC3-CAR-T cells exhibited superior anticancer efficacy over single CAR-T use in heterogeneous HCC cells and patient-derived xenograft (PDX) HCC xenografts. Our study highlights the potential of HBsAg/GPC3 dual-CAR approaches to enhance therapeutic outcomes and safety in HCC treatment.

Background: Stomach adenocarcinoma (STAD) remains a leading cause of cancer-related mortality worldwide, with limited prognostic biomarkers and heterogeneous responses to immunotherapy. Endoplasmic reticulum stress (ERS) plays a critical role in tumor progression and immune modulation, yet its comprehensive prognostic value in STAD has not been systematically characterized. This study aims to identify ERS-related genes with prognostic significance and elucidate their role in the tumor microenvironment. Methods: RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects were integrated to identify differentially expressed ERS-related genes. Univariate Cox regression and consensus clustering were applied to define molecular subtypes. A prognostic risk model was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression and validated in independent Gene Expression Omnibus (GEO) cohorts (GSE66229, GSE14208). Immune infiltration, functional enrichment, and mutation landscapes were analyzed. Single-cell RNA sequencing (scRNA-seq) (GSE183904) and CellChat were used to explore FKBP10 expression and intercellular communication. Immunohistochemistry and in vitro assays [Cell Counting Kit-8 (CCK-8), flow cytometry] were performed to validate FKBP10 function. Results: We identified 33 prognostic ERS-related genes, which classified STAD patients into two subtypes (C1 and C2) with distinct survival outcomes and immune infiltration profiles. A 14-gene risk model was constructed and stratified patients into high-and low-risk groups with significant survival differences [area under the curve (AUC) =0.702]. Risk scores correlated with age, tumor (T), metastasis (M), and overall stage. Single-cell analysis revealed FKBP10 was predominantly upregulated in fibroblasts within the tumor microenvironment, and high FKBP10 expression enhanced intercellular communication, particularly between fibroblasts and epithelial cells. Immunohistochemistry confirmed FKBP10 overexpression in STAD tissues, and FKBP10 silencing suppressed proliferation and induced S-phase arrest in HGC27 and MKN1 cells. Conclusions: This study establishes a robust ERS-related prognostic signature for STAD and highlights FKBP10 as a key regulator in the tumor microenvironment. FKBP10 promotes gastric cancer (GC) cell proliferation and reshapes cellular communication, offering a potential biomarker and therapeutic target. These findings provide a foundation for personalized prognostic assessment and immunotherapy strategies in STAD.

Gastric cancer remains a paradigm of therapeutic recalcitrance, driven by a complex ecosystem where therapeutic efficacy is dictated by the dynamic interplay between genomic instability and the tumor immune microenvironment. While biomarkers such as programmed death-ligand 1 expression and microsatellite instability currently guide therapeutic decisions, they offer only a static glimpse into a spatially and temporally evolving landscape. In this mini-review, we systematically delineate the co-evolution of spatial architecture, metabolic rewiring, and microbial interactions that orchestrate immune evasion in gastric cancer. We dissect how specific “cellular neighborhoods” – governed by the interplay between myofibroblastic cancer-associated fibroblasts and intratumoral microbiota like Fusobacterium nucleatum – construct physical and biological barriers to T-cell infiltration. Furthermore, we explore “invisible“ drivers of resistance, highlighting the synergistic potential of ferroptosis and pyroptosis in reshaping immunogenicity and the emerging role of the neuro-immune axis. Finally, we evaluate the clinical utility of next-generation biomarkers, ranging from tertiary lymphoid structure maturity and circulating tumor DNA molecular kinetics to artificial intelligence-driven “digital twins”. By integrating these multi-dimensional insights, we propose a strategic framework for precision immuno-oncology, transitioning from static profiling to holistic ecosystem engineering.

LBA4 Background: In the prespecified interim analysis of progression-free survival (PFS) from the HARMONi-6 study, ivonescimab combined with chemotherapy significantly improved PFS compared with tislelizumab plus chemotherapy in patients with previously untreated advanced squamous NSCLC(sq-NSCLC). Here we report the results of the prespecified overall survival (OS) analysis. Methods: Patients with previously untreated stage III-IV sq-NSCLC were randomly assigned (1:1) to receive ivonescimab 20 mg/kg every 3 weeks (Q3W) or tislelizumab 200 mg Q3W, each in combination with paclitaxel (175 mg/m²) and carboplatin (AUC 5) for 4 cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. Randomization was stratified by disease stage (IIIB/IIIC versus IV) and PD-L1 tumor proportion score (TPS; ≥1% versus <1%). The primary endpoint was PFS assessed by independent radiographic review committee per RECIST v1.1. OS was a key secondary endpoint and was hierarchically tested using a closed sequential testing procedure. PFS was tested first at one-sided α level of 0.025, OS was tested at the same α only after statistical significance for PFS was established. This analysis represents the first planned OS analysis with an efficacy boundary of one-sided P=0.0049. Results: A total of 532 patients were randomly assigned (n=266 per arm). As of February 27, 2026, at a median follow-up of 21.4 months, ivonescimab plus chemotherapy significantly improved OS compared with tislelizumab plus chemotherapy. Median OS was 27.9 months (95% CI, 27.89 to NE) with ivonescimab plus chemotherapy versus 23.7 months (95% CI, 20.11 to NE) with tislelizumab plus chemotherapy (hazard ratio [HR], 0.66; 95% CI, 0.50 to 0.87; one-sided P =0.0017), meeting the prespecified boundary (P<0.0049) for statistical significance.The OS benefit was consistent across prespecified subgroups. Among patients with PD-L1 TPS <1%, median OS was NE versus 18.6 months (HR, 0.64; 95% CI, 0.43 to 0.96). Among patients with PD-L1 TPS≥1%, median OS was NE versus 27.3 months (HR, 0.68; 95% CI, 0.46 to 0.99). The safety profile of ivonescimab plus chemotherapy was manageable and consistent with prior reports, with no new safety signals observed. Conclusion: Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared with tislelizumab plus chemotherapy in previously untreated patients with advanced sq-NSCLC. Notably, ivonescimab plus chemotherapy is the first regimen to show clinical superiority over an active PD-1 inhibitor control arm in the first-line setting. The dual-targeted approach of ivonescimab delivers improved survival outcomes with a favorable risk-benefit profile, establishing a compelling new standard of care in the management of advanced sq-NSCLC. Clinical trial information: NCT05840016 .

Background Diarrhea is the most common adverse event of pyrotinib. This study analyzed the association between diarrhea and survival in patients with HER2-positive advanced breast cancer treated with pyrotinib-based therapy. Methods A secondary analysis was performed using the individual patient data from the nationwide, prospective real-world PRETTY study. Baseline and treatment characteristics were summarized in groups by severity of diarrhea. Multivariable Cox regression analysis was used to analyze the association of diarrhea with real-world progression-free survival (rwPFS) and overall survival (OS), respectively. Immortal-time bias was adjusted using the landmark analysis and time-dependent Cox model. Multiple imputation was performed for missing data, and pooling ln(hazard ratio [HR]) estimations on the association between diarrhea and survival were reported. Results Of 1129 patients, 826 (73.2%) had any-grade treatment-related diarrhea (including 174 [15.4%] with grade ≥3 diarrhea). After multiple imputation, the multivariable Cox regression analysis showed that diarrhea was independently associated with longer OS (grade 1-2 diarrhea vs. none: HR=0.57 [95% CI, 0.38-0.86], P=0.007; grade ≥3 diarrhea vs. none: HR=0.56 [95% CI, 0.31-0.99], P=0.047) but was not associated with rwPFS. Significant association between diarrhea and OS was also observed in the 1-month landmark analysis (grade 1-2 diarrhea vs. none: HR=0.59 [95% CI, 0.39-0.89], P=0.012; grade ≥3 diarrhea vs. none: HR=0.54 [95% CI, 0.30-0.98], P=0.043). Time-dependent Cox model indicated the trend on better OS when diarrhea occurred, but without statistical significance. Conclusion For patients with HER2-positive advanced breast cancer, diarrhea that occurs during pyrotinib-based therapy maybe a prognostic marker of longer OS.

Objective To evaluate the clinical efficacy and adverse events of immunotherapy in patients with resectable microsatellite instability-high/mismatch repair–deficient (MSI-H/dMMR) colorectal cancer (CRC). Methods A total of 106 patients with stage II–III MSI-H/dMMR CRC treated at The Affiliated Hospital of Xuzhou Medical University from May 2018 to August 2024 were enrolled and divided into a chemotherapy group (n = 52) and an immunotherapy group (n = 54). The chemotherapy group received capecitabine monotherapy, mFOLFOX, or CAPEOX according to treatment tolerance, whereas the immunotherapy group received envafolimab, serplulimab, or camrelizumab. Clinical efficacy and adverse events were compared between the two groups. Results MSI-H/dMMR CRC was more prevalent in the right colon, and its incidence declined with advancing tumor stage. The 3-year disease-free survival (DFS) rate in the immunotherapy group was 88.9%, which was higher than that in the chemotherapy group (71.2%, P < 0.05). Notably, immunotherapy conferred more pronounced benefits in right-sided colon cancer than in left-sided disease. The immunotherapy group showed improved safety relative to the chemotherapy group. Conclusions For patients with MSI-H/dMMR CRC after radical resection, adjuvant immunotherapy provides superior efficacy compared with conventional adjuvant chemotherapy and is associated with milder adverse events, supporting its further clinical application. Trial Registration MR3226035724, registered on 20260508. Retrospectively registered.

Gastric cancer remains one of the most prevalent malignancies globally. As early-stage gastric cancer is typically asymptomatic or presents with non-specific symptoms, most patients are diagnosed at advanced stages, leading to poor survival outcomes. Effective early detection strategies are important for reducing gastric cancer-related mortality. In this study, we developed a non-invasive assay utilizing cell-free DNA to distinguish patients with early-stage gastric cancer from healthy individuals. We performed low-depth whole genome sequencing to profile cell-free DNA and extracted three distinct features: fragment size patterns, coverage at transcription factor binding sites, and methylation-based profiles. These features were integrated via machine learning to construct a stacked ensemble model. The study included a training cohort (108 gastric cancer patients and 108 healthy controls), a temporally independent validation cohort (79 patients and 79 healthy controls), and an external validation cohort recruited from two independent centers (136 patients and 136 healthy controls). The ensemble model demonstrated robust performance, achieving area under the curve values of 0.986, 0.978, and 0.967 in the training, validation, and external cohorts, respectively. Specificity and sensitivity were 98.1

Gastric cancer (GC) has a generally unfavorable prognosis. Elderly patients often tolerate dual-drug chemotherapy poorly, experience limited benefits from monotherapy, and face high rates of postoperative recurrence and metastasis. To address this unmet clinical need, this study evaluates the efficacy and safety of Yiqi Huayu Jiedu Decoction (YHJD) combined with chemotherapy in preventing recurrence and metastasis in elderly patients with stage II/III GC after surgery. This is a multicenter, double-blind, randomized, placebo-controlled trial conducted across twelve hospitals in China. A total of 302 elderly GC patients (age ≥ 65 years) with pathological stage pII/pIII after D2 resection will be randomized in a 1:1 ratio into the experimental group (n = 151) and the control group (n = 151). Patients will receive a 6-month treatment. The primary outcome is disease-free survival (DFS), and secondary outcomes include overall chemotherapy completion rate, overall survival (OS), Traditional Chinese Medicine (TCM) syndrome scores, and quality of life (QoL) assessments. Safety indicators such as adverse events (AEs), as well as exploratory analyses including big data analytics and gut microbiota diversity, will also be evaluated. Subgroup analyses will be conducted to explore the heterogeneity of YHJD effects. The results of this randomized controlled trial will provide objective evidence for evaluating YHJD as an adjuvant therapy after GC surgery, contributing to an integrated treatment strategy combining TCM and chemotherapy to prevent postoperative recurrence and metastasis in elderly GC patients. International Traditional Medicine Clinical Trial Registry, available at: http://itmctr.ccebtcm.org.cn/. Trial Registration number: ITMCTR2025001062. Registered on 09 May 2025.

BACKGROUND:Bispecific antibodies targeting programmed death 1 (PD-1) and vascular endothelial growth factor (PD1-VEGF) have shown promising efficacy in non-small-cell lung cancer (NSCLC). In our previous report of the HARMONi-6 study, we aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC. Ivonescimab combined with chemotherapy significantly prolonged progression-free survival compared with tislelizumab plus chemotherapy. Here we report the prespecified interim overall survival analysis. METHODS:HARMONi-6 is a double-blind, randomised, phase 3 trial, which was conducted at 50 hospitals across China. Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Eligible patients were randomly assigned in a 1:1 ratio to receive ivonescimab or tislelizumab, in combination with paclitaxel and carboplatin for four cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Overall survival was a key secondary endpoint; an interim analysis was planned when approximately 225 overall survival events were observed, but it was triggered after 204 overall survival events to meet regulatory deadlines. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrials.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS:From Aug 17, 2023, to Jan 21, 2025, 761 patients were assessed for eligibility, and after 229 exclusions a total of 532 patients were randomly allocated (266 per group). 494 (93%) of patients were male and 38 (7%) of patients were female. The median age was 64 years (IQR 59-69). At data cutoff (Feb 27, 2026), 204 deaths had occurred: 84 (32%) patients in the ivonescimab plus chemotherapy group and 120 (45%) in the tislelizumab plus chemotherapy group. With a median follow-up of 21·4 months (95% CI 20·27-21·91), the median overall survival was 27·9 months (95% CI 27·89-not evaluable [NE]) with ivonescimab versus 23·7 months (20·11-NE) with tislelizumab (hazard ratio for death 0·66 [95% CI 0·50-0·87]; pone-sided=0·0017), meeting the prespecified boundary (p<0·0049). The overall survival benefit with ivonescimab plus chemotherapy was consistent across key subgroups. Treatment-related adverse events of grade 3 or higher occurred in 184 (69%) of 266 patients in the ivonescimab group and 156 (59%) of 265 patients in the tislelizumab group. The incidence of grade 3 or higher haemorrhage was seven (3%) of 266 and two (1%) of 265, respectively. INTERPRETATION:Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival compared with tislelizumab plus chemotherapy in previously untreated patients with advanced squamous NSCLC. This regimen could provide a novel treatment option as first-line treatment in this patient group. FUNDING:Akeso Biopharma.

BackgroundThe aim of this study was to evaluate whether the addition of thalidomide to camrelizumab plus pemetrexed disodium and carboplatin as first-line treatment would improve therapeutic efficacy in patients with non-squamous non-small cell lung cancer (NSCLC).MethodsThis prospective, single-arm, pilot study enrolled treatment-naïve patients with advanced non-squamous NSCLC. Patients received intravenous administration of camrelizumab (200 mg), carboplatin (area under curve, 5 mg/mL per min) and pemetrexed disodium (500 mg/m2) on day 1 of each three-week treatment cycle. Meanwhile, all the patients received the maintenance therapy with thalidomide (oral, 50 mg, twice a day). Primary endpoint was progression-free survival (PFS).ResultsAt data cutoff (February 2025), 20 patients (median age 64.0 [Interquartile range, IQR:59.5–68.0]; 80% male) were evaluable. With median follow-up of 28.9 months (95%CI:16.1–45.7), the regimen achieved median overall survival (OS) of 43.3 months (95%CI:16.9–69.7) and PFS of 15.2 months (95%CI:7.6–27.5). Objective responses occurred in 70% (14/20; 95%CI:44.0–81.2%), with disease control in 95% (19/20). Treatment-related adverse events (TRAEs) affected 90% (18/20), predominantly grade 1–2 hypothyroidism (75%) and reactive cutaneous capillary endothelial proliferation (50%). Grade ≥3 TRAEs occurred in 5% (only pneumonia, elevated alanine aminotransferase, and rash).ConclusionsThe addition of thalidomide to the regimen of camrelizumab plus pemetrexed disodium and carboplatin led to a lower-than-expected incidence of RCCEP (50%, all Grade 1-2) and improvements in mPFS, mOS in advanced non-squamous NSCLC patients.

Blood lead levels were associated with increased mortality in cancer patients, with mediation analyses suggesting a partial role of oxidative stress and inflammation, and heterogeneity across cancer types linked to Hallmark pathway activity. We analyzed 2,689 cancer patients from NHANES (1999–2016) using Cox regression, restricted cubic spline, and mediation analyses. Over 22,151.5 person-years, 983 deaths occurred. Compared with the lowest quartile, the highest blood lead quartile was associated with increased all-cause mortality (HR = 2.44; 95

Objective:The study was to explore the clinical effect of the Evidence-Based and Multidisciplinary pain management program for patients after hepatectomy. It examined the program's impacts on postoperative pain, active pain, quality of life, and satisfaction with pain control. Methods:A quasi-experimental study was conducted at the Affiliated Hospital of Xuzhou Medical University from May 2024 to April 2025. Fifty-seven patients were enrolled to the experimental (n = 29) and control (n = 28) group. The experimental group was provided evidence-based pain management program by the Acute Pain Service Team. The primary outcome was pain level measured using The Numerical Rating Scale scores. Data were harvested at at the time points of transferring to the ward after surgery, 4 h, 12 h, 24 h, 48 h and 72 h after operation. Secondary outcomes were the Four Grade Functional Activity Score, the Houston Pain Outcome Instrument (HPOI) and quality of life at discharge. Results:Lower NRS scores were observed in the experimental group compared to the control group at 4 h (t = -3.979, P < 0.001), 12 h (t = -2.426, P = 0.019), 24 h (t = -4.192, P < 0.001), 48 h (t = -2.924, P = 0.005) and 72 h (t = -2.797, P = 0.007) after operation. Significant between-group differences were found in the impact of pain on deep breathing at 12 h (z = -3.472, P = 0.001), 24 h (z = -2.217, P = 0.027), 48 h (z = -2.316, P = 0.021), and 72 h (z = -2.166, P = 0.030), coughing at 24 h (z = -2.446, P = 0.014), 48 h (z = -2.803, P = 0.005), and 72 h (z = -2.580, P = 0.010), turning over at 48 h (z = -2.639, P = 0.008) and 72 h (z = -2.493, P = 0.013), and getting out of bed for activities at 48 h (z = -2.205, P = 0.027) and 72 h (z = -3.151, P = 0.002) after operation. The experimental group showed significant differences from the control group in all dimensions of HPOI. There were no differences regarding psychological and social functions. Conclusion:The Evidence-Based and Multidisciplinary pain management program improved postoperative pain, reduced impact of pain on functional activities, and enhanced satisfaction with pain control, but failed to improve psychological and social functions.

Abstract Background: Tumor-infiltrating lymphocyte (TIL) therapy has demonstrated activity in solid tumors but remains constrained by T-cell exhaustion and an immunosuppressive tumor microenvironment. GT201 is an engineered, cytokine-armored TIL product expressing membrane-bound IL-15 (mbIL-15) designed to enhance TIL persistence and antitumor function. A multi-center, open-label, single-arm exploratory clinical study was initiated to evaluate the safety, tolerability, and preliminary efficacy of GT201 in patients with advanced solid tumor. Method: The primary endpoint was to evaluate the tolerance and safety profile according to CTCAE v5.0. Secondary endpoints included preliminary efficacy measures such as overall response rate (ORR), disease control rate (DCR), assessed per RECIST v1.1, as well as pharmacokinetics of GT201. Exploratory endpoint included longitudinal tumor biopsies and peripheral blood sampling, analyzed by single-cell RNA/TCR sequencing and bulk TCR sequencing to track clonal dynamics and identify tumor-specific TCRs. Result: As of November 4, 2025, twelve patients were enrolled (median age 52.5 years; median of two prior lines of therapy). GT201 demonstrated a favorable safety profile: most AEs were Grade 1-2, while Grade ≥3 events were attributable to lymphodepleting chemotherapy or IL-2 support and resolved within 14 days. Preliminary efficacy signals were encouraging, with an ORR of 58.3% (7/12) and a DCR of 83.3% (10/12), including two complete responses (16.7%) and five partial responses (41.7%). Correlative multi-omics profiling revealed that mbIL-15-expressing cells were enriched in post-infusion tumor samples, and their corresponding TCRs underwent marked clonal expansion. A putative tumor-specific T-cell subset (4-1BB+CD8+ with high effector/exhaustion and low stemness signatures in tumor samples pre- and post-infusion) was preferentially expanded during manufacturing and showed a pronounced expansion peak in peripheral blood between Days 7-28 in responders. This subset was scarce at baseline and exhibited minimal expansion in non-responders. In contrast, “TIL-only” TCRs, which were clonotypes present in the infused product but absent pre-infusion, did not expand in peripheral blood in any patient. Conclusion: GT201 exhibited a manageable safety profile and encouraging early efficacy in patients with advanced solid tumor, with ongoing enrollment to further inform clinical outcomes. Integrated multi-omics analyses indicate that expansion of tumor-specific TCRs, during both manufacturing and post-infusion in responding patients, correlates more strongly with clinical benefit than expansion of TIL-only TCRs. Continued longitudinal sampling and functional validation of putative tumor-specific clonotypes will be essential to establish their utility as biomarkers of response in GT201 therapy. Citation Format: Pin Wang, Rong Zhou, Yong Han, Zhengxiang Han, Weijia Fang, Kai Chen, Youguo Chen, Liqing Ma, Lili Lu, Derun Shen, Jiahui Jin, Yiyang Tan, Ke Liu, Zhenjiang Liu, Jingman Wang, Zhao Xu, Jingwei Sun, Jun Cui, Jing Yu, Yue He, Yarong Liu. Armored TIL GT201 induces potent tumor-specific TCR expansion and durable antitumor responses in advanced solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5257.

BACKGROUND Postoperative complications are common in patients with gastric cancer (GC) and are closely associated with poor prognosis; however, effective tools for preoperative risk stratification remain limited. AIM To investigate the predictive value of the immune-nutritional score (INS) for postoperative complications and survival outcomes in patients with GC. METHODS We retrospectively reviewed the medical records of 247 patients with GC who underwent curative surgery between January 2019 and December 2022. Postoperative adverse events were categorized using the Clavien-Dindo grading system. Receiver operating characteristics (ROC) curve analyses were performed to evaluate the predictive value of the neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), serum albumin (Alb), and lymphocyte count for postoperative complications. Based on cutoff values, 155 patients were assigned to the low-INS group and 92 to the high-INS group. Overall survival between groups was assessed using Kaplan-Meier survival analysis. RESULTS Significant differences were found in body mass index, lymphocyte count, neutrophil count, NLR, Alb, and CRP. Lymphocyte count and Alb were protective factors, whereas neutrophil count, NLR, and CRP were independent risk factors for complications. CRP and Alb showed relatively high predictive performance (area under the receiver operating characteristic curve = 0.9047 and 0.7854, respectively), while INS demonstrated the highest predictive value (area under the receiver operating characteristic curve = 0.9710, 95% confidence interval: 0.9515-0.9904). The incidence of postoperative complications was higher in the high-INS group, and overall survival was lower in the high-INS group (P < 0.001). CONCLUSION INS is an effective predictor of postoperative complications and survival outcomes in patients with GC, with strong clinical applicability.

BACKGROUND:Squamous non-small-cell lung cancer (NSCLC) is associated with worse clinical outcomes than non-squamous NSCLC, but treatment options are scarce. We aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC. METHODS:We conducted a randomised, double-blind, phase 3 trial at 50 sites across China (HARMONi-6). Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Patients were randomly assigned (1:1) to receive intravenous ivonescimab (20 mg/kg) or tislelizumab (200 mg), plus intravenous paclitaxel (175 mg/m2) and carboplatin (area under the curve 5 mg/mL per min) once every 3 weeks for four cycles, followed by ivonescimab (20 mg/kg) or tislelizumab (200 mg) monotherapy as maintenance treatment for up to 24 months. Randomisation was stratified by disease stage (IIIB or IIIC vs IV) and PD-L1 tumour proportion score (≥1% vs <1%). The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrial.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS:From Aug 17, 2023, to Jan 21, 2025, 761 patients were screened for eligibility, among whom 532 (70%) patients were enrolled and randomly assigned to receive ivonescimab plus chemotherapy (266 [50%] patients) or tislelizumab plus chemotherapy (266 [50%] patients). As of Feb 28, 2025, median follow-up time was 10·3 months (95% CI 9·5-11·0). Median progression-free survival was 11·1 months (95% CI 9·9-not evaluable) in the ivonescimab group and 6·9 months (5·8-8·6) in the tislelizumab group (hazard ratio 0·60 [95% CI 0·46-0·78]; one-sided p<0·0001). The progression-free survival benefit with ivonescimab plus chemotherapy was consistent regardless of PD-L1 status. 170 (64%) patients in the ivonescimab group and 144 (54%) patients in the tislelizumab group had grade 3 or higher treatment-related adverse events, with grade 3 or higher immune-related adverse events occurring in 24 (9%) patients in the ivonescimab group and in 27 (10%) patients in the tislelizumab group. Grade 3 or higher treatment-related haemorrhage occurred in five (2%) patients in the ivonescimab group and in two (1%) patients in the tislelizumab group. INTERPRETATION:In patients with untreated advanced squamous NSCLC, ivonescimab plus chemotherapy showed significantly improved progression-free survival compared with tislelizumab plus chemotherapy, regardless of PD-L1 status, as well as a manageable safety profile. This regimen could be used as a novel first-line treatment in this patient group. FUNDING:Akeso Biopharma.

ObjectiveTo investigate the efficacy of anlotinib, an antiangiogenic multikinase inhibitor, as an add-on therapy to first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) for patients with EGFR-mutant non-small cell lung cancer (NSCLC) who were previously untreated before first-line EGFR TKI but subsequently developed oligoprogression.MethodsThis multicenter, retrospective cohort study (ALTER-L058) analyzed data from the electronic health records-derived de-identified systems at 16 cancer centers in China. Adult patients between 18 and 75 years of age with histologically or cytologically confirmed locally advanced or metastatic NSCLC who received first-line third-generation EGFR TKI monotherapy and had an oligoprogressive disease were included. Eligible patients received anlotinib (8, 10 or 12 mg) on days 1–14 of each 3-week cycle for ≥6 cycles. Tumor response was assessed radiologically by investigators per RECIST, version 1.1. The primary outcome was investigators-assessed progression-free survival, calculated from the date of medication initiation for the oligoprogressive disease to the first documented progressive disease or death.ResultsBetween January 2020 and December 2023, 100 patients received EGFR TKI plus anlotinib and 50 received EGFR TKI. At the data cutoff (20 November 2024), the median progression-free survival was 9.23 months (95% CI, 8.94–10.87) with EGFR TKI plus anlotinib versus 5.42 months (95% CI, 4.83–6.80) with EGFR TKI (hazard ratio [HR] = 0.38, 95% CI, 0.26–0.56; log rank test, P < 0.0001), meeting the primary endpoint. Anlotinib was generally well tolerated, with manageable adverse events.ConclusionAnlotinib, when added onto EGFR TKI therapy following gradual progression or oligo-progression, conferred significant PFS benefits upon EGFR mutant NSCLC patients, supporting adding anlotinib to ongoing first-line EGFR TKI therapy for oligoprogressive disease.