ABSTRACT Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR‐mutant non–small‐cell lung cancer (NSCLC) is heterogeneous, and serial re‐biopsy may uncover actionable mechanisms. We report a 55‐year‐old man with stage IVB lung adenocarcinoma harboring EGFR L858R and TP53 R282W. First‐line icotinib produced a partial response (PR) with progression‐free survival (PFS) of 7 months. Rebiopsy at progression identified acquired EGFR T790M together with a MET c.3010C>G exon 14‐related alteration. Almonertinib induced a second PR lasting 7 months. After renewed progression, almonertinib plus savolitinib achieved another PR for 8 months, supporting MET‐dependent bypass resistance. Biopsy of a newly progressive iliac metastasis then showed emergence of RET‐CCDC6 fusion, whereas T790M and the MET alteration were no longer detected. Because selective RET inhibition was initially unaffordable, the patient received pemetrexed‐carboplatin plus continued almonertinib, followed by selpercatinib plus almonertinib. Local radiotherapy to oligoprogressive bone and lung lesions prolonged benefit from systemic therapy. At the latest follow‐up in January 2026, the patient remained alive nearly 50 months after diagnosis. This case illustrates clonal evolution under treatment pressure and highlights three practical lessons: repeat molecular testing at each clinically meaningful progression, matched combination targeted therapy for actionable bypass alterations, and local ablative radiotherapy for oligoprogression.

Abstract Purpose Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognosis. This phase 2 study evaluated the efficacy and safety of surufatinib plus programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors as maintenance therapy in patients with ES-SCLC without disease progression after first-line chemoimmunotherapy. Methods Patients with ES-SCLC and with non-progressive disease after 4–6 cycles of platinum-based chemotherapy plus PD-1/PD-L1 inhibitors received oral surufatinib 250 mg once daily plus PD-1/PD-L1 therapy. The primary endpoint was progression-free survival (PFS) assessed by investigators. Results A total of 21 patients (71.4% aged under 65 years; 61.9% with 5–6 induction cycles) were enrolled between 19 September 2022 and 30 June 2023 and received ≥ 1 study treatment. The median PFS was 4.0 months (95% CI: 1.9–6.4) from maintenance therapy initiation and 8.8 months (95% CI: 6.5–13.4) from induction therapy initiation. From initiation of maintenance treatment, median overall survival (OS) was not reached after 17.1 months of follow-up and the 18-month OS was 57.1% (95% CI: 33.8–74.9). Among 13 patients with measurable lesions at baseline, the objective response rate was 23.1% (95% CI: 5.0–53.8), and disease control rate was 53.8% (95% CI: 25.1–80.8). Treatment-related adverse events (TRAEs) occurred in 19 patients (90.5%), with grade ≥ 3 TRAEs reported in six patients (28.6%). Two patients (9.5%) discontinued due to TRAEs; no treatment-related deaths occurred. Conclusions Surufatinib combined with PD-1/PD-L1 inhibitors as first-line maintenance therapy showed encouraging PFS and a tolerable safety profile in patients with ES-SCLC who received chemotherapy combined with PD-1/PD-L1 inhibitors as first-line induction therapy. Trial registration ClinicalTrials.gov, NCT05509699. Registered 16 August 2022, https//clinicaltrials.gov/study/NCT05509699.

e16399 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited therapeutic options in advanced stages. Building upon the foundational evidence from the PAN-HEROIC-1 trial which demonstrated the clinical benefits of irinotecan liposome (II) and supported its approval for unresectable locally advanced or metastatic PDAC in China, this study aimed to evaluate the real-world safety and effectiveness of irinotecan liposome (II)-based combination regimens in patients with PDAC. Methods: This multicenter, prospective, real-world study included patients with pathologically or radiologically confirmed PDAC who were considered eligible by investigators for irinotecan liposome (II)-based combination regimens incorporating chemotherapy, chemoradiation, radiotherapy, immunotherapy, or targeted therapy. Patients were assigned to three cohorts according to treatment stage at enrollment: perioperative, first-line, and later-line treatment. Observational data were collected including adverse events, baseline characteristics, therapeutic regimens, and tumor response. The primary endpoint was treatment-emergent adverse events (TEAEs); secondary endpoints included overall survival (OS) and real-world progression-free survival (rwPFS), real-world time to progression (rwTTP), real-world objective response rate (rwORR), real-world disease control rate (rwDCR), real-world disease-free survival (rwDFS) and real-world duration of treatment (rwDOT). Results: As of August 30, 2025, a total of 236 patients were enrolled (perioperative, n = 23; first-line, n = 98; later-line, n = 115). The median age was 62.0 years (range, 33.0–83.0), with males and females accounting for 57.2% and 42.8%, respectively. Tumors were located in pancreatic head (25.4%), pancreatic body (11.4%), pancreatic tail (11.4%) and other pancreatic sites (51.7%). The most frequent metastasis site was the liver (39.0%). Baseline CA19-9 ≥37 U/mL was observed in 81.8% of patients. Any-grade TEAEs occurred in 36.9% of patients, with the most common being anemia (7.2%), nausea (6.8%), diarrhea (6.8%) and leukopenia (5.1%); grade ≥3 TEAEs occurred in 7.2% of patients. Median rwPFS was not reached in any cohort; the 6-month rwPFS rates were 83.3%, 66.4%, and 41.1% for the perioperative, first-line, and later-line cohorts, respectively. The median OS was not reached in any of the three cohorts. Conclusions: This real-world study revealed that the combination regimen based on irinotecan liposome (II) showed a manageable safety profile and encouraging effectiveness signals. Follow-up and patient enrollment are ongoing.

Digestive system cancers represent a group of malignancies with high global incidence and a particularly heavy disease burden in China. Among these, gastric cancer, colorectal cancer, and biliary tract cancer represent critical human epidermal growth factor receptor 2 (HER2)-positive subtypes that require focused clinical attention. Antibody–drug conjugates (ADCs), which utilize HER2-targeted monoclonal antibodies to deliver cytotoxic agents directly to tumor cells, have revolutionized precision therapy in HER2-positive cancers, marking a significant milestone in oncologic treatment. Currently, trastuzumab deruxtecan and disitamab vedotin have been approved for the treatment of advanced gastric cancer. This expert consensus emphasizes the safety management of HER2 ADCs in digestive system cancers, considering the unique anatomical complexity and the vulnerability of the mucosal barrier in this system. It underscores the essential role of multidisciplinary team collaboration in standardizing the management of adverse events and offers evidence-based recommendations to guide clinical practice across primary and secondary care settings. Furthermore, it underscores the value of a “physician-led, patient-engaged” model in patient education. The safety management experience accumulated in this context also offers important insights for the clinical application of ADCs targeting other oncogenic pathways.

Purpose:The outcomes of different antidiarrheal strategies in HER2-positive breast cancer patients treated with pyrotinib plus trastuzumab and docetaxel are unknown. Materials and Methods:97 eligible patients received pyrotinib once daily from Cycle 1 Day 7 onwards, combined with intravenous trastuzumab and docetaxel on Day 1 of each 21-day cycle. In the 400PYR cohort, patients were treated with 400 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the 320PYR+Pro-L and 400PYR+Pro-L cohorts, patients were given 320 or 400 mg pyrotinib and loperamide prophylaxis. In the 320PYR cohort, patients were treated with 320 mg pyrotinib, without mandatory antidiarrheal prophylaxis. In the PYR-DE+Pro-L cohort, patients were treated with escalating pyrotinib doses and loperamide prophylaxis. Results:The incidence of grade 3 diarrhea in cohorts with loperamide prophylaxis was lower than in the 400PYR cohort. In the 3 cohorts with loperamide prophylaxis, the dose escalation cohort had the lowest incidence of grade 3 diarrhea. The incidence of grade 3 diarrhea in 320PYR cohort was similar to the 3 cohorts with prophylactic antidiarrheal loperamide. No event of grade 4 or 5 diarrhea was reported. Conclusion:Loperamide prophylaxis and pyrotinib dose escalation were associated with lower observed rates of grade 3 diarrhea in patients receiving pyrotinib plus trastuzumab and docetaxel. The lower rate observed in the 320PYR cohort should be interpreted cautiously and may reflect improved clinical management rather than a reproducible protocolized intervention.

In this phase 2 study (NCT05047991), patients with unresectable metastatic pancreatic adenocarcinoma were randomized to receive NALIRIFOX (liposomal irinotecan, 5-FU, leucovorin, and oxaliplatin) or gemcitabine plus nab-paclitaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included other efficacy outcomes (overall survival, objective response rate, disease control rate, and duration of response), as well as safety, pharmacokinetic parameters, and evaluation of the relationship between UGT1A1*6 and UGT1A1*28 polymorphisms and safety. A total of 117 patients were enrolled and randomly assigned to NALIRIFOX (n = 78) or gemcitabine plus nab-paclitaxel (n = 39). At a median follow-up of 18.7 months (interquartile range [IQR], 7.5–22.1) for NALIRIFOX and 12.1 months (IQR: 6.4–14.8) for the gemcitabine plus nab-paclitaxel, median PFS was 7.6 months (95

Background:Programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors improve survival in driver-negative advanced non-small cell lung cancer (NSCLC); however, their efficacy in oncogene-driven NSCLC has not yet been established. This study evaluated the clinical and molecular predictors of immunotherapy outcomes in this population. Methods:We conducted a retrospective, two-center cohort study of 129 patients with advanced NSCLC harboring driver mutations who received PD-1/PD-L1 inhibitors (either as monotherapy or in combination with other antineoplastic drugs). Treatment efficacy and predictors were analyzed in the overall cohort and key mutational subgroups, including epidermal growth factor receptor (EGFR)- and Kirsten rat sarcoma (KRAS)-mutant NSCLC. We examined the efficacy of immunotherapy and assessed the correlation between treatment responses in 77 patients who received both immunotherapy and targeted therapy. Results:The efficacy of immunotherapy varied significantly by genotype. Patients with KRAS mutations, a subgroup characterized by a higher prevalence of smoking history and elevated PD-L1 expression, demonstrated superior outcomes compared to those with EGFR, human epidermal growth factor receptor 2 (HER2), or other rare mutations. Multivariate analysis identified smoking history, high PD-L1 expression, and receipt of first-line immunotherapy as independent predictors of progression-free survival (PFS) in the overall cohort. Among the patients with EGFR mutations, receipt of first- or second-generation (1G/2G) tyrosine kinase inhibitors (TKIs) alone prior to immunotherapy, Threonine 790 Methionine (T790M) mutation-negative status, and the Leucine 858 Arginine (L858R) subtype were associated with improved outcomes. However, multivariate analysis showed that a history of treatment with 1G/2G TKIs only was the sole independent predictor of PFS. In KRAS-mutant patients, smoking history and high PD-L1 expression were positive predictors of PFS in the multivariate analysis. Smokers with a tumor proportion score (TPS) ≥1% achieved a median PFS of 19.0 months, compared with 8.5 months for non-smokers with a TPS ≥1% and 1.5 months for non-smokers with a TPS <1% (P<0.001). Targeted therapy was associated with a significantly longer median PFS than immunotherapy in both the overall cohort and the EGFR- and rare-mutation subgroups. No correlation was observed between responses to targeted therapy and subsequent immunotherapy. Conclusions:KRAS-mutant NSCLC is characterized by a high proportion of patients with a smoking history and elevated PD-L1 expression, which may contribute to its superior response to immunotherapy compared with other mutation subtypes. In the overall driver-positive population, smoking history, high PD-L1 expression, and receipt of first-line treatment were associated with immunotherapy benefits. Among the patients with EGFR-mutant NSCLC, prior treatment limited to 1G/2G TKIs was associated with better subsequent immunotherapy efficacy. Among the patients with KRAS-mutant NSCLC, smoking history and high PD-L1 expression were associated with improved immunotherapy outcomes. Overall, targeted therapy demonstrated superior efficacy than immunotherapy in this cohort. The efficacy of prior targeted therapy did not predict subsequent response to immunotherapy.

BackgroundBladder cancer (BLCA) is a prevalent malignancy worldwide, with advanced stages linked to poor prognosis. Although immune checkpoint inhibitors (ICIs) show clinical promise in treating both operable and advanced BLCA, predicting patient responses remains a major challenge. Glutamine metabolism, a key aspect of metabolic reprogramming, has been implicated in tumor progression and immune modulation. However, the exact role of glutamine metabolism in BLCA remains poorly understood. This study aims to explore its association with clinical outcomes and immunotherapy response while functionally validating key regulatory genes.MethodsAn integrated approach combining targeted metabolomics, single-cell RNA sequencing, and bulk transcriptomic data was used to profile glutamine metabolism in BLCA comprehensively and identify potential metabolic biomarkers. A prognostic model, termed GMscore, based on glutamine metabolism, was constructed using principal component analysis (PCA). Key regulatory genes were identified through random forest analysis. Functional assays, including in vitro proliferation, migration, and metabolic assays, as well as in vivo xenograft models, were employed to validate the findings.ResultsTargeted metabolomics revealed increased glutamine metabolism in BLCA cell lines. The GMscore model, developed and validated across multiple cohorts, accurately predicted patient survival. In two immunotherapy cohorts (IMvigor210 and GSE91061), a lower GMscore correlated with improved therapeutic response, suggesting its potential as a predictive biomarker for immunotherapy efficacy. PYCR1 was identified as a key regulatory gene, exhibiting high expression in epithelial cells and cancer-associated fibroblasts (CAFs). Functional assays demonstrated that PYCR1 knockdown inhibited cell proliferation and migration and suppressed tumor growth in vivo. Mechanistically, PYCR1 facilitated proline synthesis through P5CS and activated the PI3K/AKT/mTOR signaling pathway, which modulated glutamine utilization and metabolic reprogramming in BLCA.ConclusionsThis study provides a comprehensive analysis of glutamine metabolism in BLCA and introduces a clinically relevant prognostic model. PYCR1 was identified as a central metabolic regulator, underscoring its critical role in tumor development and progression.

This study is a first-in-human, three-stage, phase 1 trial (NCT05154604) designed to evaluate the trophoblast cell-surface antigen 2 (TROP-2)-targeted antibody-drug conjugate SHR-A1921 (1.5-6.0 mg/kg every 3 weeks) in 391 patients with pretreated advanced/metastatic solid tumors. Grade ≥3 treatment-related adverse events occurred in 132 patients (33.8%), with the most common being stomatitis, affecting 57 patients (14.6%). SHR-A1921 showed a low incidence of hematologic toxicities, with only 3.1% of patients experiencing grade ≥3 decreases in neutrophil count. The overall objective response rate was 24.8% (95% confidence interval [CI], 20.6-29.4), ranging from 18.2% to 43.1% across cohorts with platinum-resistant ovarian cancer, triple-negative breast cancer, small-cell lung cancer, non-small cell lung cancer, hormone receptor-positive breast cancer, cervical cancer, and biliary tract cancer. No significant correlation was found between TROP-2 expression and treatment efficacy. In summary, SHR-A1921 exhibited promising antitumor activity and a manageable safety profile, with 3.0 mg/kg every 3 weeks selected for further clinical development.

Patients diagnosed with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) typically have an immunosuppressive tumor microenvironment, which leads to a low response rate when treated with immunotherapy. Some studies indicate that chemotherapy and anti-angiogenic therapy could potentially improve the responsiveness of these patients to immunotherapy. Therefore, this study is designed to assess the effectiveness and safety of combining chemotherapy with bevacizumab and anti-PD-1 immunotherapy as a second-line treatment option for MSS mCRC. A retrospective analysis was conducted on patients diagnosed with MSS mCRC at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024. Patients received second-line chemotherapy in combination with bevacizumab and anti-PD-1 immunotherapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and treatment-related adverse reactions were collected. Biomarker analysis was performed to identify potential predictors of a favorable treatment response. Between January 2021 and December 2024, 29 patients were enrolled. Five patients (17.2%) achieved a partial response (PR), and 18 patients (62.1%) had stable disease. The median follow-up period was 13.3 months. The ORR was 17.2%, and the DCR was 79.3%. The median PFS was 7.8 months, and the median OS was 28.8 months. The most common treatment-related adverse events (TRAEs) of all grades were anemia (18/29, 62.1%), leukopenia (12/29, 41.4%), and hand-foot syndrome (10/29, 34.5%). The most frequent grade 3 or 4 TRAEs were anemia (2/29, 6.9%) and elevated triglycerides (1/29, 3.4%). No grade 5 adverse events occurred. Dynamic changes in the Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), and Platelet-to-Inflammatory Index (PIV) before and after treatment could predict the efficacy of immune combination therapy. In the biomarker exploration, multiple immunohistochemical analyses indicated better tumor immune microenvironment cell infiltration in the PFS-long (≥ 16 weeks) group compared to the PFS-short group. Chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC, with manageable adverse reactions. Exploratory biomarker assessment analysis showed that hematological dynamic changes and tumor immune microenvironment cell infiltration may predict the efficacy of immune combination therapy.

e14670 Background: IMM27M is a humanized Fc-engineered IgG1 CTLA-4 monoclonal antibody with enhanced ADCC. In pre-clinical models, IMM27M could enhance immune responses and promote Treg depletion. The pre-clinical results showed IMM27M induced a significantly stronger anti-tumor activity than ipilimumab and resulted in complete tumor remission even at a low dose. Methods: This study is an open-label, multi-center, phase I dose-escalation study conducted to evaluate the safety, tolerability, maximum tolerated dose/recommended dose for expansion, PK and anti-tumor activity in patients with advanced solid tumors. The study was designed with an accelerated titration followed by a standard 3+3 design. IMM27M (0.1,0.3,1,2,3 mg/kg) was administered as monotherapy on Day 1 of every 3 weeks. Results: As of 30 Dec 2022, the dose has been escalated to 2mg/kg. 11 pts (8 female, 3 male) were enrolled and treated (1 at 0.1 mg/kg, 3 at 0.3 mg/kg, 3 at 1.0 mg/kg, 4 at 2.0 mg/kg), including 3 pts with melanoma, 3 pts with breast carcinoma, 2 pts with RCC, 1 pt with HCC, 1pt with NSCLC and 1 pt with ovarian carcinoma. Median age was 52 years (range 36-72). 9 pts (81.8%) received ≥ 2 lines of previous systemic therapies and 7 pts (63.6%) received previous anti PD-1/PD-L1 treatment. Treatment-related adverse events (TRAEs) occurred in 10 pts (90.9%) to date. Most TRAEs were grade 1 or 2. The most common TRAEs (≥ 10%) of all grades were anaemia (n = 3 [27.3%]), white blood cell count decreased (n = 2 [18.2%]), lymphocyte count decreased (n = 2 [18.2%]), constipation (n = 2 [18.2%]) and rash (n = 2 [18.2%]). Grade ≥3 TRAEs occurred in 2 pts (18.2%): lymphocyte count decreased (G3, n = 1 [9.1%]) and immune-related lung disease (G3, n = 1 [9.1%]). Treatment related SAE patients only occurred in 1 pt (immune-related lung disease, possibly related to treatment), and this patient recovered after clinical treatment. No DLT was observed. No TRAE leading to treatment discontinuation was reported. In 10 response evaluable pts, 3 pts had SD as best response. One pt in 2.0 mg/kg dose cohort had tumor shrinkage of 17% at Week 6, who had metastatic melanoma and received 2 lines of previous treatments including anti PD-1. The treatment of this patient is ongoing. Preliminary PK analysis of IMM27 showed an approximate proportional dose curve and the mean t 1/2 was around 11 days. Conclusions: IMM27M monotherapy in general was well-tolerated at the dose level evaluated and preliminarily anti-tumor activity in patients with advanced solid tumors. The dose escalation study of IMM27M in advanced solid tumors is ongoing. Clinical trial information: NCT05235438 .

BACKGROUND:Clinical trial evidence points to chemotherapy's potential in augmenting the effects of immunotherapy. AIM:To assess the effectiveness of first-line chemoimmunotherapy (CIT) for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) verses standard-of-care (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab). METHODS:This was a multicenter retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received first-line treatment were eligible. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate progression-free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). PFS was set as the primary endpoint. Propensity score (PS) was calculated to balance the baseline characteristics of the two cohorts. With PS, we performed three statistical methods, namely inverse probability weighting, PS matching, and additional adjustment for PS with multivariate cox regression. RESULTS:Between July 2019 and November 2024, 148 eligible patients were enrolled, with 40 and 108 patients assigned to the CIT and SOC cohorts, respectively. At a global median follow-up of 21.4 months, the crude median PFS was 13.5 months (95%CI: 9.77-21.6) in the CIT cohort vs 9.1 months (95%CI: 7.8-10.6) in the SOC cohort, yielding a nonsignificant hazard ratio (HR) of 0.5645 (95%CI: 0.3637-0.8763, P = 0.01; SOC as reference). Multivariate Cox regression analysis, adjusted for sex, age > 60 years, Eastern Cooperative Oncology Group performance status, rat sarcoma mutation, primary tumor location (left vs right) and number of metastatic organs (liver/lung), demonstrated an adjusted HR of 0.55 (95%CI: 0.35-0.87, P = 0.011). PS-based analyses using PS matching (post-matching n = 40 vs 40), PS-adjusted multivariate Cox regression, and inverse probability weighting revealed consistent significant trends favoring CIT, with HRs for CIT of 0.5641 (95%CI: 0.3303-0.9635, P = 0.0361), 0.60 (95%CI: 0.38-0.96, P = 0.034), and 0.57 (95%CI: 0.337-0.973, P = 0.039), respectively. CONCLUSION:Efficacy of CIT in MSS mCRC could surpass that of standard first-line chemotherapy. Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from CIT.

Background: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare neoplastic entity classified in the 2021 World Health Organization Classification of Thoracic Tumors. Due to its rarity, challenges remain in achieving accurate diagnosis, determining optimal therapeutic strategies, and assessing prognosis. Patient Presentation: An elderly heavy smoker was admitted due to the rapid growth of a solid tumor in the right lower lobe. Histopathological examination revealed undifferentiated, epithelioid morphology. Immunohistochemistry demonstrated diffuse positivity for SOX2, alongside loss of expression of brahma-related gene 1 (BRG1) and brahma (BRM). Next-generation sequencing identified a nonsense mutation in SMARCA4 (c.2196T > G, p.Y732Ter), with wild-type status for SMARCA2. The tumor was staged as T1N2M0 (stage IIIA), exhibiting a programmed death-ligand 1 tumor proportion score of 2%, a tumor mutational burden of 16.3 mutations per megabase (Mb), and microsatellite stability. The patient received neoadjuvant chemo-immunotherapy followed by right lower lobectomy, resulting in a complete pathological response with ypT0N0Mx status. Subsequently, 5 cycles of adjuvant chemo-immunotherapy were administered. Throughout a 38-month follow-up period, neither computed tomography imaging nor minimal residual disease assessments indicated evidence of recurrence or metastasis. Conclusion: The diagnosis of SMARCA4-UT requires the co-loss of BRG1 and BRM expression, characteristic histological features, and the exclusion of other SMARCA4-deficient thoracic malignancies. This tumor exhibits aggressive clinical behavior, limited availability of targeted therapeutic options, and only modest responses to conventional chemotherapy. The present report underscores the potential efficacy of immune checkpoint inhibitors as a viable treatment modality for SMARCA4-UT.

BACKGROUND:Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) is characterized by an immunosuppressive tumor microenvironment, leading to limited efficacy of immunotherapy in these patients. Clinical trial data suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients. However, whether these research findings can be "replicated" in clinical practice still requires further validation through real-world studies. This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-programmed death 1 (PD-1) immunotherapy as the first-line regimen for MSS mCRC in the real world. AIM:To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the first-line regimen for MSS mCRC in the real world. METHODS:We conducted a retrospective analysis of patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital between January 2020 and December 2024. Patients were stratified into two treatment groups: (1) An experimental group receiving first-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy; and (2) A control group receiving chemotherapy plus bevacizumab alone. Propensity score matching was employed to balance baseline characteristics, including age, gender, Eastern Cooperative Oncology Group performance status, number of metastatic sites, and primary tumor location. The primary endpoints were progression-free survival and overall survival, while secondary endpoints included disease control rate, objective response rate, and treatment-related adverse events. Survival outcomes were assessed using Kaplan-Meier analysis with log-rank testing. Additionally, inverse probability of treatment weighting was applied for sensitivity analysis to validate the robustness of our findings. RESULTS:The propensity score matching analysis identified 103 well-balanced patient pairs with a median follow-up of 25.5 months. The experimental group demonstrated numerically higher objective response (36.00% vs 23.08%, P = 0.309) and disease control rates (96.00% vs 91.03%, P = 0.6759) compared to the control group, though these differences were not statistically significant. Similarly, no significant survival benefit was observed for either progression-free survival [hazard ratio (HR) = 0.7076, 95% confidence interval (CI): 0.4069-1.23, P = 0.22] or overall survival (HR = 1.154, 95%CI: 0.4712-2.827, P = 0.75). Multivariate analysis identified liver metastases as an independent poor prognostic factor (HR = 3.36, 95%CI: 1.71-6.60, P < 0.001), while subgroup analyses revealed potential benefits of the experimental regimen in male patients (HR = 0.33, 95%CI: 0.14-0.81, P = 0.025) and those with right-sided primary tumors (HR = 0.40, 95%CI: 0.17-0.95, P = 0.022). Safety profiles were comparable between groups, though elevated lactate dehydrogenase emerged as an independent risk factor for poorer outcomes in the experimental group (HR = 4.11, 95%CI: 1.02-16.55, P = 0.046). CONCLUSION:Chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy could not demonstrate promising efficacy in treating MSS mCRC compared to the standard first-line chemotherapy regimen with bevacizumab. Male patients or those with right-sided mCRC may derive benefits from immune-based combination therapy. Further research is needed to investigate specific clinical characteristics or biomarkers to identify patients who may derive benefit from combined immunotherapy approaches.

Muscle-invasive bladder cancer (MIBC) continues to pose a significant health challenge, as conventional neoadjuvant chemotherapy (NAC) has shown limited improvements in efficacy outcomes. Recent clinical trials suggest that combining NAC with immune checkpoint blockade (NAC.NICB) may enhance therapeutic efficacy. This study aimed to explore the short-term therapeutic efficacy and outcomes of NAC.NICB compared to NAC in real-world settings for the treatment of MIBC. A total of 100 patients with MIBC who received either NAC or NAC.NICB were included in the study. The treatment efficacy of the NAC and NAC.NICB groups was evaluated based on pathological complete response (pCR) and the rate of pathological downstaging through post treatment pathological assessment. In the NAC.NICB group, clinical characteristics were compared between patients who achieved pCR and those who did not, using the independent samples t-test or the Mann-Whitney U test. Overall, 71 patients received NAC and 29 patients received NAC.NICB. At baseline, the NAC.NICB group exhibited higher T and N stages compared to the NAC group. However, 48.3% (14/29) of the patients in the NAC.NICB group achieved pCR, which was significantly higher than that observed in the NAC group (18/71, 25.4%; p = 0.034). In addition, the pathological downstaging rate in the NAC.NICB group was higher than that of the NAC group (75.9% vs. 47.9%; p = 0.014). The disease control rate (DCR) in the NAC.NICB group was higher than that observed in the NAC group (96.6% vs. 77.5%; p = 0.020). Higher pretreatment hemoglobin levels (p = 0.018) or lower platelet levels (p = 0.026) in patients undergoing NAC.NICB therapy may serve as a potential predictor for achieving a higher pCR rate. Neoadjuvant chemotherapy combined with immune checkpoint blockade improves pCR and pathological downstaging rates in MIBC, highlighting the benefits of neoadjuvant chemoimmunotherapy for MIBC.

Noninvasive odor sensing is important in environmental monitoring and medical diagnosis. The two-dimensional material MXene is widely used due to its unique sensing properties but has limitations in specifically recognizing a certain gas. This study developed a bioinspired biosensor array (BBA) whose core mechanism involved programming MXene sensing interfaces through DNA base sequences to mimic molecular recognition principles of biological olfactory receptors. Integrated with machine learning algorithms, the BBA achieved preliminary identification of cancer patients by detecting exhaled gas samples from different populations. Starting from DNA molecular length, base type, and chemical modification, different DNAs were prepared and screened by orthogonal experiments to obtain five DNA/MXene composite biosensing materials with excellent sensing properties. Combined with pure MXene, a Six-channel bioinspired biosensor Array(6C-BBA) was established, and a neural network algorithm was utilized for the preliminary validation of the real odor molecules of fruits. Finally, the high-performance 6C-BBA was used to detect breath samples from stomach cancer patients, lung cancer patients, intestinal cancer patients, and healthy people, and the array showed 86.3, 94.1, 89.5, and 86.3% accuracy. This study could offer a specific method for advanced biosensor development and reveal important applications in early noninvasive recognition of diseases.

Introduction:The majority of head and neck squamous cell carcinomas (HNSCC) are diagnosed at an advanced stage, often necessitating standard treatments such as surgery or concurrent chemoradiotherapy. Methods:This was a real-world study conducted between January 2021 and October 2024. The study enrolled 42 previously untreated patients diagnosed with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Patients received induction chemotherapy (IC) with or without immunotherapy followed by radiotherapy at our hospital. Results:The group receiving immunotherapy with IC (I+IC, N=26) demonstrated an 82.6% objective response rate (ORR) and a 92.3% disease control rate (DCR). In contrast, patients treated with IC (N=16) alone exhibited an ORR of 37.5% and a DCR of 93.8%. With a median follow-up of 28.9 months, the I+IC group showed a 100% 6-month progression-free survival (PFS) and an 88.5% 12-month PFS, with a 92.3% overall survival (OS) rate at 12 months. Discussion:This real-world study suggests that the addition of immunotherapy to IC holds promise for improving treatment outcomes in locally advanced HNSCC. The findings underscore the need for further research involving a larger patient population to validate these preliminary results.

BACKGROUND:Targeted therapy combined with anti-programmed cell death 1 immunotherapy (TP) and trifluridine/tipiracil (TAS-102) combined with bevacizumab (TB) are two common therapies for patients with late-line therapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). However, it is still unclear which therapy can bring better prognosis. AIM:To evaluate the effectiveness and safety of TP vs TB as the late-line regimen for MSS mCRC in the real world. METHODS:This is a dual-center retrospective cohort study conducted in Peking University First Hospital and Jilin Cancer Hospital. Patients with MSS mCRC who had received at least the second line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-free survival (PFS) was set as the primary endpoint. The Kaplan-Meier method and Cox proportional hazard model were used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Landmark analysis was performed to create segmented survival curves, studying the impact of treatment regimen on prognosis during different follow-up periods. RESULTS:Between July 2019 and March 2025 (data cutoff), 127 eligible patients were enrolled, with 88 and 39 patients assigned to the TP and TB cohorts, respectively, based on treatment allocation. At a global median follow-up of 9.73 months, the crude median PFS was 3.9 months (95%CI: 3.03-5.53) in the TP cohort vs 4.17 months (95%CI: 2.87-5.6) in the TB cohort, yielding a nonsignificant HR of 1.43 (95%CI: 0.94-2.18, P = 0.092; TB as reference). Multivariate Cox regression analysis, adjusted for sex, age > 60 years, Eastern Cooperative Oncology Group performance status, RAS mutation, primary tumor location (left vs right), number of metastatic organs (liver/lung), and treatment line (≥ 3rd line), demonstrated an adjusted HR of 1.23 (95%CI: 0.80-1.88, P = 0.348). PS-based analyses using three methodologies: Inverse probability weighting, PS matching (post-matching n = 55 vs 30), and PS-adjusted multivariate Cox regression. These analyses revealed consistent nonsignificant trends favoring TB, with HRs for TP of 1.26 (95%CI: 0.76-2.10, P = 0.077), 1.42 (95%CI: 0.87-2.34, P = 0.164), and 1.26 (95%CI: 0.76-2.10, P = 0.367), respectively. Notably, landmark PFS analyses at 90, 120, and 150 days demonstrated a significantly higher proportion of TP patients maintaining disease control beyond these timepoints (P = 0.048, 0.031, and 0.035, respectively), suggesting sustained clinical benefits in TP responders. CONCLUSION:TP and TB demonstrated similar PFS in both crude and PS-adjusted analyses. However, patients who derived benefits from TP therapy exceeding 90 days showed more sustained clinical advantages compared to TB. Our study suggests that for patients with MSS mCRC who respond to TP therapy in later-line treatments, this regimen could provide additional prolonged clinical benefits, which warrants further validation through large-scale cohort investigations.