IntroductionHER2-low breast cancer has emerged as a distinct molecular subtype with unique biological features and therapeutic significance. Trastuzumab deruxtecan, an antibody-drug conjugate, has shown promising efficacy in both HER2-high and HER2-low disease.Case descriptionWe report the case of a 69-year-old woman with a 17-year history of breast cancer, initially diagnosed in 2007 with invasive ductal carcinoma and lymph node metastasis. After multiple lines of systemic therapy, the disease progressed with dynamic reduction of HER2 expression from 3+ to 1+, ultimately confirming HER2-low advanced breast cancer. Recurrent malignant pleural effusion became the predominant manifestation, severely impairing quality of life.Intervention and outcomesDS-8201 monotherapy was initiated but failed to control pleural effusion. Sequential combinations of DS-8201 with intrapleural cisplatin and then intrapleural bevacizumab were attempted, with only the latter yielding significant benefit. The regimen was subsequently optimized to intravenous DS-8201 plus bevacizumab, resulting in rapid symptom relief, substantial reduction of pleural effusion, and sustained disease control. At the latest follow-up, the patient achieved 18 months of stable disease with improved quality of life and no severe adverse events.ConclusionTo our knowledge, this is the first reported case of DS-8201 plus bevacizumab for HER2-low metastatic breast cancer with malignant pleural effusion. This case highlights the potential of this regimen as a promising therapeutic option for patients with limited alternatives.

Postacute sequelae of COVID-19 (PASC), a multisystem disorder with prevalent respiratory manifestations, affecting millions of individuals worldwide, yet the organ-/system-specific PASC pathogenesis and targeted interventions remain largely undefined. In this longitudinal cohort study of individuals followed up at 4 (n = 57) and 7 months (n = 54) after the Omicron BA.5 outbreak in China, we comprehensively analyzed physician-administered PASC symptom assessments, clinical respiratory evaluations (pulmonary function and chest computed tomography), immunological response profiles, and inflammatory markers. Our findings demonstrated that patients with respiratory system-specific PASC (R-PASC) endure long-term pulmonary function impairment (restrictive ventilation and diffusion dysfunction), sustained severe residual lung lesions (predominant fibrosis), and chronic systemic inflammatory responses. Patients with R-PASC exhibited enhanced SARS-CoV-2-specific T-cell responses, whereas in the control group, moderate-magnitude and polyfunctional virus-specific T-cell response correlated with improved lung function and alleviated inflammation. Sustained neutralizing antibody titers were also observed in patients with R-PASC, whereas humoral responses showed minimal association with disease pathophysiology. Moreover, prolonged activation of complement classical and alternative pathway in patients with R-PASC is associated with worsening respiratory parameters, whereas mannose-binding lectin within the lectin pathway exhibits protective correlations with pulmonary tissue function preservation. Overall, our study delineates the extensively perturbed immune-inflammation-organ dysfunction in patients with R-PASC, thereby providing valuable insights into the pathogenesis of this condition and highlighting potential targets for therapeutic intervention.

Importance The ASTRUM-005 phase 3 randomized clinical trial showed substantial survival benefit from adding serplulimab to chemotherapy for previously untreated extensive-stage small cell lung cancer (ES-SCLC). However, the long-term outcomes are unclear. Objective To investigate the efficacy, safety, patient-reported outcomes (PROs), and exploratory biomarker findings from ASTRUM-005 at an extended follow-up. Design, Setting, and Participants This international, double-blind, phase 3 randomized clinical trial enrolled patients from September 12, 2019, to April 27, 2021 in China, Russia, Ukraine, Poland, Turkey, and Georgia. Eligible patients had histologically or cytologically confirmed ES-SCLC with no prior systemic therapy. Patients were followed up through May 7, 2024, and the data analysis of this prespecified, secondary analysis lasted from August to September 2024. The median follow-up duration was 42.4 months (range, 0.2-55.2). Exposures Patients were randomized in a 2:1 ratio to receive intravenous serplulimab (4.5 mg/kg; serplulimab group) or placebo (placebo group), which was combined with up to 4 cycles of carboplatin and etoposide every 3 weeks. Main outcomes and measures The primary end point was overall survival (OS). Secondary end points included other efficacy end points, safety, and PROs. Results A total of 585 patients (median [range] age was 63 [28-76] years in the serplulimab group and 62 [31-83] years in the placebo group) with previously untreated ES-SCLC, and 389 (66.5%) were randomly assigned to the serplulimab group and 196 (33.5%) to the placebo group. Baseline characteristics were balanced across treatment groups. At data cutoff, 280 OS events (72.0%) in the serplulimab group and 166 (84.7%) in the placebo group were observed. Compared with the placebo group, the serplulimab group showed more favorable efficacy (median OS, 15.8 [95% CI, 13.9-17.4] vs 11.1 [95% CI, 10.0-12.4] months; hazard ratio, 0.60; 95% CI, 0.49-0.73; P < .001). The serplulimab group showed improved OS rates at 4 years compared with the placebo group (21.9% vs 7.2%). Grade 3 or higher serplulimab-related or placebo-related treatment-emergent adverse events occurred for 136 (35.0%) and 57 patients (29.1%) in the respective groups. A PRO analysis revealed consistent trends of improved overall health, dyspnea, and pain in both groups and faster recovery from alopecia in the serplulimab group. Conclusions and Relevance This secondary analysis of a randomized clinical trial demonstrated long-term benefit from adding serplulimab to chemotherapy for previously untreated patients with ES-SCLC, supporting this therapy as a first-line standard of care for this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT04063163

e15508 Background: Postoperative management of colon cancer relies on the accurate interpretation of complex pathology reports and adherence to evolving clinical guidelines. However, manual assessment is time-consuming and prone to numerical errors, resulting in staging misclassification and guideline-discordant therapy. Utilizing Large Language Models (LLMs) to bridge the gap between raw clinical data and standardized decision-making, while enhancing patient communication, remains an unmet clinical need. Methods: We developed and verified an LLM-based Clinical Decision Support System (CDSS) utilizing a dataset of 4,608 pathology reports from two tertiary hospitals and 409 cases from TCGA. The system implements a standardized "pathology-to-decision" workflow comprising five key modules: (1) Automated Staging: Extraction of unstructured data to automate TNM staging (AJCC 8 th edition) with explicit reasoning and field tracing; (2) Risk Stratification: Classification of MMR status and assessment of high-risk factors (e.g., lymph nodes < 12, perineural invasion) to distinguish high-risk from low-risk patients; (3) Decision Support: Generation of guideline-concordant treatment recommendations and follow-up schedules calculated from the surgery date (NCCN Guidelines 2025 v4); (4) Prognostic RAG: A PubMed-based Retrieval-Augmented Generation module that synthesizes patient demographics and pathology features to answer queries regarding 5-year survival, recurrence windows, and genetic screening necessity; and (5) Patient Education: Simplification of complex reports into patient-friendly summaries. Results: Comparative analysis with manual expert review demonstrated that the CDSS significantly reduced the average time required for case processing by 98.3% (approx. 9.8s vs. 578.9s per case). In performance validation, the system achieved an accuracy of 96.8% for TNM staging and 97.9% for risk stratification, and reduced guideline-discordant treatment decisions. The PubMed-RAG module provided evidence-based prognostic information, and the patient summaries showed improved readability scores compared to original reports (Table 1). Conclusions: The CDSS improves postoperative staging accuracy, supports guideline-concordant treatment and surveillance, and facilitates patient-centered risk counseling. It provides a scalable approach to standardizing management of colon cancer across diverse clinical settings. Comparison of postoperative decision support approaches. Feature CDSS Manual Practice Staging Logic Deterministic (Rule-based) Experience-dependent Guideline adherence Real-time (AJCC/NCCN) Manual updates Traceability Fully traceable (Linked to source) Manual cross-checking Multilingual pathology support Yes Limited Patient support Integrated, guideline-based Time-consuming Time per Case < 10 seconds 5-10 minutes

e15725 Background: Deficient mismatch repair (dMMR) colorectal cancer is a biologically heterogeneous disease. Tumors from different anatomical sites arise from distinct embryonic layers and show variable clinical behavior, including differing responses to immunotherapy. However, large-scale studies systematically examining how tumor location influences dMMR patterns and associated clinicopathologic features remain limited. Methods: We retrospectively analyzed 1,021 patients with dMMR colorectal cancer confirmed by immunohistochemistry. Tumors were classified by location (right-sided colon, left-sided colon, rectum) and by dMMR pattern (MLH1/PMS2 loss, MSH2/MSH6 loss, isolated PMS2 loss, isolated MSH6 loss, and others. Clinicopathologic features were compared across locations and patterns using univariate and multivariable analyses. Results: Significant differences in dMMR patterns were observed across anatomical sites (P < 0.001). Right clon were predominantly MLH1/PMS2 loss (67.9%), while rectal showed higher prevalence of isolated PMS2 loss (30.9%). Left colon were more frequently associated with MSH2/MSH6 and isolated MSH6 loss. Clinically, right colon was characterized by larger diameters (P = 0.006), whereas rectal was significantly associated with younger age (P = 0.001), male sex (P = 0.034), and higher Ki-67 expression (P = 0.05). Multivariable analysis confirmed that dMMR subtype is an independent predictor of tumor location, specifically with MLH1/PMS2 loss strongly associated with right colon cancer. Conclusions: Our findings highlight the significant anatomical and clinicopathologic heterogeneity within dMMR colorectal cancer. These site-specific differences in dMMR subtypes and tumor aggressiveness may stem from distinct embryological origins. Consequently, dMMR alone is insufficient for clinical stratification; anatomical location and specific deficiency subtypes must be integrated to enable precise risk assessment and individualized therapeutic decision-making. Multivariable analysis of clinicopathologic factors associated with tumor location in dmmr colorectal cancer. Variable Right Colon VS Left Colon OR (95% Cl) P-value Rectum VS Left Colon OR (95% Cl) P-value Age (＜65 VS ≥65) 0.719 (0.444,1.163) 0.179 0.413 (0.247,0.691) 0.001 Sex (Male VS Female) 0.788 (0.489,1.268) 0.325 1.752 (1.043,2.942) 0.034 Maximum tumor diameter 1.164 (1.045,1.296) 0.006 0.794 (0.702,0.898) 0.000 Perineural Invasion (No VS Yes) 1.144 (0.446,2.932) 0.779 0.269 (0.112,0.651) 0.004 Ki-67 (Low VS High) 0.803 (0.260,2.481) 0.704 2.910 (0.998,8.485) 0.050 dMMR: MLH1/PMS2 loss (ref Other)dMMR: MSH2/MSH6 loss (ref Other)dMMR: MSH6 loss (ref Other)dMMR: PMS2 loss (ref Other) 3.765 (1.842,7.697)1.803 (0.761,4.274)0.805 (0.331,1.961)1.084 (0.443,2.654) 0.0000.1810.6330.859 0.810 (0.387,1.696)0.928 (0.382,2.253)0.628 (0.260,1.522)1.777 (0.772,4.087) 0.5760.8690.3030.176

BACKGROUND:First-line amivantamab plus carboplatin-pemetrexed demonstrated efficacy and an acceptable safety profile in the PAPILLON trial (NCT04538664) in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertions; we report the efficacy and safety results of the Chinese mainland subgroup population from the PAPILLON study. METHODS:PAPILLON was a randomized, open-label, multicenter, phase 3 study comparing amivantamab plus carboplatin-pemetrexed therapy with standard of care carboplatin-pemetrexed, in patients with treatment-naïve, locally advanced, or metastatic non-small-cell lung cancer characterized by EGFR exon 20 insertion mutations. Between March 2021 and October 2022, 87 treatment-naïve patients were randomized in China (amivantamab plus carboplatin-pemetrexed, 39; carboplatin-pemetrexed, 48). The primary endpoint was progression-free survival as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors v1.1. Comparison between treatment groups was conducted using a stratified log-rank test, with hazard ratios estimated from a stratified Cox proportional hazards model. RESULTS:Progression-free survival was longer in the amivantamab plus carboplatin-pemetrexed group than in the carboplatin-pemetrexed group (median, 12.3 months, 95% confidence interval [CI], 7.0 months to not evaluable vs. 6.7 months, 95% CI, 4.2-8.6 months; hazard ratio, 0.47; 95% CI, 0.26-0.85; nominal P = 0.0109). The 18-month progression-free survival rate was 33% with amivantamab plus carboplatin-pemetrexed and 12% with carboplatin-pemetrexed. The objective response rate was 71.8% (95% CI, 55.1-85.0%) with amivantamab plus carboplatin-pemetrexed and 48.9% (34.1-63.9%) with carboplatin-pemetrexed (odds ratio, 2.46; 95% CI, 1.01-5.98; nominal P = 0.0478). Median progression-free survival after first subsequent therapy was not evaluable for amivantamab plus carboplatin-pemetrexed and 18.8 months for carboplatin-pemetrexed (hazard ratio, 0.32; 95% CI, 0.11-0.88; nominal P = 0.0212). Interim overall survival analysis suggests about 42% improved chance of survival with amivantamab plus carboplatin-pemetrexed vs. carboplatin-pemetrexed. The most common adverse events with amivantamab plus carboplatin-pemetrexed were neutropenia, anemia, leukopenia, and rash. No new safety signals were observed. No patients discontinued amivantamab due to related adverse events. CONCLUSION:Results from the PAPILLON Chinese mainland population were consistent with the overall population and support the use of amivantamab plus carboplatin-pemetrexed in first-line treatment of Chinese patients with EGFR exon 20 insertion-mutated non-small cell lung cancer. TRIAL REGISTRATION:https://clinicaltrials.gov/; registration number, NCT04538664.

Background:Immunotherapy is now a cornerstone of first-line treatment for advanced gastric or gastroesophageal junction cancer (G/GEJC). However, optimal second-line options after progression on first-line immunotherapy are undefined. Given the established efficacy of cadonilimab in the first-line setting, this real-world study evaluated its combination with chemotherapy as a second-line treatment. Methods:We conducted a single-center retrospective study of patients with advanced G/GEJC progressing after first-line immunotherapy. Patients received either cadonilimab plus chemotherapy (Cohort A, n=50) or chemotherapy alone (Cohort B, n=62) as second-line therapy between October 2022 and April 2025. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results:Cohort A showed significantly improved outcomes. Median PFS was 4.9 months (95% CI: 3.9-6.0) in Cohort A vs 3.8 months (95% CI: 2.8-4.8) in Cohort B (p=0.024). Median OS was 10.3 months (95% CI: 8.8-11.8) vs 7.4 months (95% CI: 6.9-7.9), respectively (p=0.046). ORR was 34.0% vs 17.7% (p=0.048), and DCR was 74.0% vs 54.8% (p=0.036). Safety was comparable between cohorts, with no treatment-related deaths. Conclusion:Cadonilimab plus chemotherapy significantly improved efficacy outcomes versus chemotherapy alone in patients with advanced G/GEJC after first-line immunotherapy progression, with a manageable safety profile. This suggests cadonilimab based therapy is a promising second-line strategy. Further prospective randomized studies are needed to confirm these findings.

Background:Phospholipase C η1 (PLCH1), a member of the phospholipase C superfamily, has been implicated in the development of multiple cancers. However, its specific role in breast cancer progression, its association with clinicopathological features, and its prognostic significance remain unclear. Methods:PLCH1 expression was analyzed across multiple tumor types using the TNMplot database, which integrates RNA-seq, microarray, and normalized data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO), encompassing 40,442 tumor and 15,648 normal samples. Differential expression analysis was performed using boxplots and statistical tests to assess significance. DNA methylation and survival analyses were conducted using TCGA data, with Kaplan-Meier curves and Cox regression to evaluate prognostic value. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed on differentially expressed genes using the clusterProfiler package. Mutation analyses were conducted using mutation annotation format (MAF) files, and pathway activities were correlated with PLCH1 expression via single-sample GSEA (ssGSEA). Experimental validation included immunohistochemistry (IHC) on 100 breast invasive ductal carcinoma samples, real-time quantitative PCR (RT-qPCR), and Western blotting. PLCH1 knockdown functional studies assessed cell proliferation and signaling pathways. Results:PLCH1 was significantly overexpressed in various cancers, including breast cancer, compared to normal tissues. PLCH1 expression was strongly correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer tissues, further linking PLCH1 to poor prognosis and adverse patient outcomes. Functional studies revealed that PLCH1 was highly expressed in breast cancer cell lines, and PLCH1 knockdown significantly inhibited cell proliferation, induced cell cycle arrest, and reduced cyclin-dependent kinase 1 (CDK1) expression in BT-474 cells. Mechanistically, PLCH1 silencing downregulated early growth response 1 (EGR1) expression by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway, impairing tumor cell proliferation. Conclusions:PLCH1 was overexpressed in breast cancer and was associated with worse patient outcomes. Its role in promoting cell proliferation via the ERK1/2-EGR1 axis highlighted PLCH1 as a potential therapeutic target for breast cancer. These findings offer new insights into the molecular mechanisms underlying breast cancer progression and suggest promising avenues for targeted therapy development.

Background:Anlotinib and bevacizumab have demonstrated efficacy in treating HER-2 (human epidermal growth factor receptor 2)-negative metastatic breast cancer (MBC), yet no comparative studies have been conducted to access their effectiveness in MBC patients. Accordingly, this study aimed to evaluate the safety and effectiveness of anlotinib versus bevacizumab when combined with taxane/capecitabine for second-line or subsequent treatment of HER-2-negative MBC. Methods:Patients with pathologically confirmed HER-2-negative MBC that underwent second-line or subsequent treatment of anlotinib or bevacizumab plus taxane/capecitabine between April 2020 and October 2021 were retrospectively reviewed. Outcomes including the objective response rates (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Results:A total of 130 patients were included for this study, with 67 in the anlotinib + chemotherapy group and 63 in the bevacizumab + chemotherapy group. The ORRs were 40.30% for the anlotinib + chemotherapy group and 30.16% for the bevacizumab + chemotherapy group (P = 0.27), while the DCRs were 86.57% and 69.84%, respectively (P = 0.03). Patients in the anlotinib + chemotherapy group showed significantly longer median PFS and OS compared to the bevacizumab + chemotherapy group (mPFS: 8.57 vs 5.90 months, HR 0.55 [95% CI 0.36-0.85], P = 0.04; mOS: 22.76 vs 16.50 months, HR 0.63[95% CI 0.43-0.93], P = 0.02). The most common treatment-related adverse events (TRAE) were grade 1/2 alopecia, peripheral neuropathy, hypertension, and granulocytopenia, with both groups exhibiting tolerable TRAE profiles. Conclusion:In this retrospective analysis, anlotinib combined with taxane/capecitabine demonstrated a manageable safety profile. This regimen was associated with improved DCR, PFS, and OS compared to bevacizumab plus chemotherapy in patients with HER2-negative MBC. These findings suggest that anlotinib may represent a promising therapeutic option for patients for whom ADC drugs are inaccessible or unsuitable; however, further prospective, randomized studies are warranted to confirm.

BACKGROUND:GEMSTONE-302 was a phase 3 trial in patients with treatment-naive metastatic squamous or non-squamous non-small-cell lung cancer (NSCLC), showed significant improvement in progression-free survival and overall survival with sugemalimab, a PD-L1 inhibitor, plus chemotherapy versus placebo plus chemotherapy. We report the 4-year outcomes from this study. METHODS:This randomised, double-blind, phase 3 trial was conducted across 35 hospitals and academic research centres in China. Eligible patients were aged 18-75 years; had treatment-naive, histologically or cytologically confirmed stage IV NSCLC, irrespective of PD-L1 expression levels; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomised (2:1) by investigators using an interactive web response or voice response system via permuted blocks (block sizes of three or six, randomised within each stratum). Patients received histology-specific platinum-based chemotherapy combined with either sugemalimab (1200 mg; sugemalimab group) or placebo (placebo group) for up to four cycles, followed by for up to 35 cycles of maintenance therapy with sugemalimab alone for patients with squamous NSCLC and sugemalimab plus pemetrexed for patients with non-squamous NSCLC in the sugemalimab group, or placebo for patients with squamous NSCLC and placebo plus pemetrexed for patients with non-squamous NSCLC in the placebo group, administered intravenously. Treatment beyond 35 cycles was permitted at the investigator's discretion. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Here, we report post-hoc 4-year efficacy and safety outcomes from GEMSTONE-302. This study is registered with ClinicalTrials.gov (NCT03789604) and concluded on May 15, 2023, with all patients discontinued. FINDINGS:Between December 13, 2018, and May 15, 2020, 846 patients were assessed for eligibility. 479 patients were randomly assigned into the sugemalimab group (n=320) and placebo group (n=159). 254 (79%) patients were men and 66 (21%) were women in the sugemalimab group and 129 (81%) were men and 30 (19%) were women in the placebo group. All patients were Asian. As of the data cutoff on May 15, 2023, median follow-up durations were 43·5 months (IQR 41·2-46·9) in the sugemalimab group and 43·0 months (40·7-44·8) in the placebo group; median treatment durations were 7·2 months (4·2-18·8) with sugemalimab and 4·6 months (2·8-6·9) with placebo. Median progression-free survival was 9·0 months (95% CI 7·4-10·9) in the sugemalimab group versus 4·9 months (4·8-5·2) in the placebo group (hazard ratio [HR] 0·49 [95% CI 0·39-0·60]). Median overall survival was 25·2 months (20·1-30·2) in the sugemalimab group versus 16·9 months (12·8-20·7) in the placebo group (HR 0·68 [0·54-0·85]). The 4-year overall survival rates were 32·1% (95% CI 26·7-37·6) in the sugemalimab group versus 17·3% (11·1-24·7) in the placebo group. The most common grade 3-4 treatment related adverse events were decreased neutrophil count (105 [33%] with sugemalimab vs 52 [33%] with placebo), decreased white blood cell count (48 [15%] vs 27 [17%]), anaemia (44 [14%] vs 18 [11%]), and decreased platelet count (35 [11%] vs 15 [9%]). Treatment-related serious adverse events occurred in 82 (26%) patients with sugemalimab and 31 (20%) with placebo. No additional treatment-related deaths occurred since the previous overall survival interim analysis. No new safety signals were identified. INTERPRETATION:Sugemalimab with chemotherapy showed a superior long-term overall survival benefit compared with placebo with chemotherapy, as a first-line treatment for patients with NSCLC with no known sensitising EGFR, ALK, ROS1, or RET genomic alterations. These results underscore the efficacy of sugemalimab plus platinum-based chemotherapy as a standard first-line treatment option for both squamous and non-squamous metastatic NSCLC while maintaining a manageable safety profile. FUNDING:CStone Pharmaceuticals. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

3152 Background: This study aimed to evaluate the efficacy and safety of drug-loaded vesicle (DLV) intrapleural perfusion combined with systemic therapy in patients with lung or breast cancer and malignant pleural effusion (MPE). Methods: This multicenter, randomized, controlled, open-label clinical trial included patients with pathologically confirmed lung or breast cancer and MPE requiring thoracentesis. In total, 96 patients were randomised 1:1 to arm 1 receiving DLV intrapleural perfusion (50 mL daily for four consecutive days) plus systemic therapy (ST) or arm 2 receiving interleukin-2 (IL-2) intrapleural perfusion (50 mL every three days for three sessions) with ST.The primary endpoint was the objective response rate (ORR) of pleural effusion at 4 weeks post-perfusion, while secondary endpoints included overall survival (OS) and treatment-related toxicity.The difference in ORR between the two cohorts was analyzed using the Chi-square test. Kaplan-Meier survival analysis was performed for OS comparison between the two cohorts. Results: A total of 91 patients were evaluated for efficacy (50 in arm 1 and 41 in arm 2). The DLV+ST arm 1 showed a significantly higher ORR for pleural effusion than the IL-2+ST arm 2 (74.0% vs. 53.7%, P = 0.043). In the survival analysis of 83 evaluable patients, median OS was 15.0 months (95% CI: 9.2–26.9) in arm 1 and 6.9 months (95% CI: 5.3–15.8) in arm 2, without a statistically significant difference (HR = 0.75; 95% CI: 0.46–1.24; P = 0.266). The 1-, 2-, and 3-year OS rates for arm 1 were 83.0% (95% CI: 72.9–94.4%), 59.6% (95% CI: 47.1–75.4%), and 51.1% (95% CI: 38.6–67.6%), compared to arm 2's 69.4% (95% CI: 55.9–86.2%), 41.7% (95% CI: 28.3–61.3%), and 33.3% (95% CI: 21.0–52.9%). Both arms had similar safety profiles, with chemotherapy-induced toxicities, including leukopenia, gastrointestinal reactions, and liver dysfunction, being the most common treatment-related adverse events. Conclusions: Drug-loaded vesicle intrapleural perfusion combined with systemic therapy is a safe and effective treatment option for malignant pleural effusion in patients with lung or breast cancer. This approach represents a promising treatment strategy for MPE and warrants further clinical investigation and consideration in clinical practice. Clinical trial information: ChiCTR1800017104 .

In this article, folic acid (FA) modified biodegradable poly (ethylene glycol) (PEG2K) was chosen as the polymeric skeleton to conjugate with curcumin (CUR) via a disulfide bond to construct a reduction-responsive drug delivery system (FA-PEG2K-SS-CUR), aiming at improving the solubility of CUR and providing a targeted, efficient, and low side-effect anti-cancer nano-preparation. The polymers were synthesized through three steps to develop FAPEG2K-SS-CUR micelles, with a drug loading capacity of up to 10.9 % and good stability. The particle of FAPEG2K-SS-CUR micelles determined by Malvern Mastersizer was 79.14 +/- 2.2 nm, and a hemolysis assay confirmed their good biocompatibility. The reduction sensitivity of FA-PEG2K-SS-CUR micelles was verified by adding dithiothreitol (DTT) to the release medium, showing a programmed drug release mode with 60.41 % released within 72 h, indicating a certain sustained-release capability. In vitro cytotoxicity assays showed that the FA-PEG2K-SS-CUR micelles were more cytotoxic than free CUR. Additionally, FA-PEG2K-SS-CUR micelles exhibited a higher cellular uptake rate than micelles without FA. Hence, the prepared multifunctional FA-PEG2KSS-CUR micelles is a promising anti-tumor nano-preparation.

Background:HER2-positive advanced breast cancer poses significant treatment challenges. In China, T-DM1 and pyrotinib are key second-line therapies. A comprehensive evaluation of the comparative efficacy and safety profiles of these therapies is imperative for optimizing therapeutic strategies and enhancing patient outcomes. This study aims to compare the clinical efficacy and safety of T-DM1 against pyrotinib plus capecitabine. Methods:Patients are females with HER2-positive, locally advanced, or metastatic breast cancer who at least 18 years old and have received anti-HER2 therapy in the past. This study included 148 patients who satisfied the inclusion criteria. Of these, 74 patients received intravenous T-DM1 (3.6 mg/kg) every 21 days, while the other 74 patients got oral pyrotinib (400 mg, once daily) plus capecitabine (1000 mg/m2, twice daily on days 1-14 of each 21-day cycle). Progression-free survival (PFS) was the main outcome, while overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were the secondary outcomes. Results:The median PFS was 12.2 months for the pyrotinib group vs 9.1 months for the T-DM1 group. The median follow-up was 12.7 months for pyrotinib and 9.3 months for T-DM1. The pyrotinib group had better DCR (56.8% vs 54.1%) and ORR (40.5% vs 29.7%). While adverse events were manageable, the most common severe AE in the pyrotinib group was diarrhea (24.3%), and in the T-DM1 group, it was thrombocytopenia (16.2%). However, by reducing the drug dosage or providing symptomatic treatment, most adverse events could be controlled at grades 1 to 2, indicating that the adverse events were manageable. Neither group recorded any adverse event-related deaths. Conclusion:Pyrotinib plus capecitabine significantly improves median PFS compared to T-DM1 in patients with HER2-positive advanced breast cancer, demonstrating a favorable efficacy profile alongside manageable safety concerns.

We collected 96 patients who received dual immunotherapy between January 2019 and June 2024, in a 1:1:1 ratio based on PD-L1 expression levels of negative (<1%), medium (1% ≤ PD-L1 ≤ 49%), and high (PD-L1 ≥ 50%). This study evaluates the efficacy and safety of dual immunotherapy in patients with advanced NSCLC, stratified by PD-L1 expression levels. Among the 96 patients, the objective response rate (ORR) was 37.5%, disease control rate (DCR) was 67.8%. In the multivariate analysis of PFS, PD-L1 ≥ 50% (HR = 0.40, 95% CI: 0.22-0.74) was identified as a protective factor for PFS, while PS Score ≥ 2 (HR = 2.74, 95% CI: 1.11-6.77) and stage IV tumors (HR = 2.05, 95% CI: 1.02-4.12) were risk factors. In the multivariate analysis of OS, PD-L1 between 1% and 49% (HR = 0.51, 95% CI: 0.28-0.90) and PD-L1 ≥ 50% (HR = 0.31, 95% CI: 0.17-0.57) were protective factors, with no risk factors detected. The incidence of adverse events was 77.1%, with a 34.3% incidence of grade 3-4 immune-related adverse events. And PD-L1 ≥ 50% group adverse events incidence more common, with an overall incidence of 87.5% and a grade 3-4 incidence of 40.6%. Patients with high PD-L1 expression (≥50%) demonstrated improved progression-free survival (PFS, HR = 0.40) and overall survival (OS, HR = 0.31) but experienced a higher incidence of severe adverse events (40.6%).

BackgroundTo evaluate the efficacy and safety of sintilimab in combination with trastuzumab and chemotherapy for HER2-positive advanced gastric/gastroesophageal junction cancer (GC/GEJC).MethodsHER2-positive advanced GC/GEJC patients admitted to our department between January 2018 and October 2024 were included in this study. Patients who received sintilimab in combination with trastuzumab and chemotherapy were assigned to cohort A, while patients who received trastuzumab and chemotherapy alone were assigned to cohort B. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while the secondary endpoints included disease control rate (DCR), objective response rate (ORR), and safety.ResultsA total of 103 patients were analyzed, with 46 in cohort A and 57 in cohort B. The ORR was 65.2% in cohort A compared to 40.4% in cohort B, while the DCR was 87.0% in cohort A and 70.2% in cohort B. The median follow-up duration was 14.0 months. Median PFS (mPFS) was 9.4 months (95% CI: 5.6–13.2) for cohort A and 7.4 months (95% CI: 6.1–8.7) for cohort B (p = 0.089). Median OS (mOS) was 16.4 months (95% CI: 11.5–21.3) in cohort A versus 14.2 months (95% CI: 11.2–17.2) in cohort B (p = 0.069). Adverse events were predominantly mild, and no treatment-related deaths occurred.ConclusionSintilimab combined with trastuzumab and chemotherapy showed promising efficacy and acceptable safety in HER2-positive advanced GC/GEJC. However, no statistically significant improvement in survival outcomes was observed compared to trastuzumab and chemotherapy alone.

Objective:To evaluate the efficacy and safety of QL1206 (a denosumab biosimilar to Xgeva®) in breast cancer patients with bone metastasis (BM) through subgroup analysis of a randomized, double-blind phase III trial (No. NCT04550949). Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phase III trial. Patients were randomized (1:1) to receive either three cycles of QL1206 or denosumab (120 mg subcutaneously every 4 weeks). Subsequently, they received 10 cycles of QL1206 (120 mg) over 40 weeks, followed by a 20-week safety follow-up. The primary endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide corrected for creatinine (uNTx/Cr). Results:The breast cancer cohort consisted of 311 patients. Vertebral involvement (66.4%) was the most prevalent BM site at enrollment, while 27.7% of patients presented with ≥3 metastatic bone lesions. At week 13, QL1206 demonstrated a median uNTx/Cr reduction of -69.9% (range: -98.1%-568.0%) vs. -74.3% (range: -97.7%-386.3%) for denosumab. The analysis of covariance revealed comparable least-square means for log-transformed changes: -1.416 [95% confidence interval (95% CI): -1.736 to -1.096] vs. -1.501 (95% CI: -1.824 to -1.178), yielding an between-group difference of 0.085 (90% CI: -0.062-0.232; P=0.343). After a 53-week treatment period, 83.6% achieved bone density improvement/disease stabilization. Safety profiles were comparable between groups. Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer, supporting QL1206 as a new option for management of BM from breast cancer.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported. The MEDLINE, EMBASE, and the Cochrane Library databases were searched. The primary outcome was the incidence of TEs, and the secondary outcome was the relationship between TEs and overall survival (OS) following ICI therapy. A subgroup analysis of TE incidents was performed according to the TE type and combination regimens. The I2 statistic was used to determine the heterogeneity, and funnel plots and Egger's test were used to assess publication bias. A total of 16,602 patients with NSCLC in 63 experimental arms were included in the analysis. The rate of TEs ranged from 0.1% to 13.8%, and the pooled overall incidence of all-grade TEs was 3% (95% confidence interval [CI], 2%-4%). The pooled rate of high-grade TEs was 1% (95% CI, 1%-2%). The venous and arterial TE rates were 3% (95% CI, 2%-4%) and 1% (95% CI, 1%-2%), respectively. Patients who received immunotherapy + chemoradiotherapy had the highest incidence of TEs (7%). The TE pooled rate was higher in patients treated with combined ICIs than in those treated with mono ICIs (4% vs. 2%). The OS was lower in patients with TEs than in those without TEs (hazard ratio, 1.4; 95% CI, 1.02%-1.92%). The incidence of TEs in NSCLC patients treated with ICIs was reasonable. Nonetheless, clinicians must be aware of potential thrombotic complications and treat them promptly.