Izalontamab brengitecan (iza-bren) is the first approved bispecific antibody-drug conjugate (BsADC), comprising an EGFR/HER3-targeting bispecific antibody conjugated to a novel topoisomerase I inhibitor (Ed-04) via a stable tetrapeptide cleavable linker. Iza-bren demonstrated positive results by meeting the primary endpoints in registrational Phase III trials conducted in nasopharyngeal carcinoma, esophageal squamous cell carcinoma, and triple-negative breast cancer. In June 2026, iza-bren was approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with recurrent/metastatic nasopharyngeal carcinoma who have failed at least two prior lines of systemic chemotherapy and PD-1/PD-L1 inhibitor therapy; in July 2026, iza-bren was approved for the treatment of adult patients with recurrent or metastatic esophageal squamous cell carcinoma who have experienced disease progression after prior therapy with a PD-1/PD-L1 inhibitor in combination with platinum-containing chemotherapy. As a first-in-class antineoplastic agent, iza-bren is poised for widespread clinical application following its approval. To optimize patient outcomes, this consensus, developed by 182 clinical experts across multiple tumor types through iterative discussions, provides guidance on the safe and effective use of iza-bren and the clinical management of its associated adverse events.
Objective: This study aimed to investigate the prevalence and epidemiological characteristics of cervical human papilloma virus (HPV) infection among ethnic minority and Han Chinese women in Honghe Hani and Yi Autonomous Prefecture of Yunnan Province to provide a theoretical basis for the strategy of cervical cancer prevention and treatment in this region. Methods: A consecutive cohort of 12,605 female residents who underwent cervical HPV genotyping across four medical centers in the Honghe Hani and Yi Autonomous Prefecture between January 2018 and June 2024 was enrolled. The overall HPV prevalence and genotype distribution was analyzed and the disparities in infection patterns among different ethnic groups were compared. Results: The overall HPV prevalence among women in this region was 17.88% (2,254/12,605). Infections solely with high-risk HPV (HR-HPV) predominated, with a prevalence of 14.75%, accounting for 82.48% (1,859/2,254) of all HPV-positive cases. The three most prevalent HR-HPV genotypes were HPV-52 (4.53%), HPV-16 (2.41%), and HPV-58 (2.01%). HPV infections exhibited a striking age-specific clustering among younger demographics; the prevalence in both the <20 and 20-29 years age groups reached 100%. The prevalence declined significantly with advancing age, dropping to 5.20% in the ≥60 years age group. Single-genotype infections constituted the primary pattern (74.00%, 1,668/2,254). However, multiple infections-particularly mixed infections of HR-HPV and low-risk HPV (LR-HPV)-were exceptionally prominent in the <20 years age group, peaking at 24.14%. Demographically, the overall HPV prevalence among ethnic minority women was significantly higher than that of Han women (23.14% vs. 15.62%, P＜0.001), with the highest rates observed in the Dai (27.10%), Hani (26.30%), and Miao (25.17%) ethnicities. Although the general infection patterns (single vs. multiple) were similar between ethnicminority and Han women, ethnicminority women bore a significantly higher burden of specific HR-HPV types compared with Han women, including HPV-16 (3.56% vs. 1.92%), HPV-58 (3.03% vs. 1.58%), HPV-51 (2.45% vs. 1.24%), and HPV-59 (0.92% vs. 0.30%) (all P＜0.05). Furthermore, inter-ethnic variations in genotype distribution were observed among the minority groups; notably, the distribution of HR-HPV-56 showed the most significant difference (P=0.018), with the highest prevalence found in women from the Dai ethnicity (3.74%). Conclusions: Cervical HPV infections among women in this region are predominantly driven by HR-HPV types 52, 16, and 58, exhibiting significant age and ethnic heterogeneity. Young women aged <30 years are highly susceptible not only to overall HPV infection, but also to mixed exposure involving multiple genotypes. Compared to Han women, ethnic minority women face a substantially more severe burden of HR-HPV infections. These findings suggest that future cervical cancer prevention and control strategies in this region should shift interventions to earlier stages, prioritizing early screening and health education for young women. Simultaneously, it is imperative to account for ethnic disparities, promote multivalent HPV vaccines that cover the predominant endemic strains, and develop targeted, precision-based prevention strategies tailored to specific ethnic regions.
Objective: To investigate the anti-colorectal cancer effect of tremella fuciformis polysaccharides (TFP) via the gut microbiota-metabolite axis. Methods: Colorectal cancer was induced in C57BL/6J mice using azoxymethane/dextran sulfate sodium. TFP or distilled water was administered by gavage for 3 weeks. Disease activity index (DAI), colon length, tumor burden, histopathology, gut microbiota (metagenomics), fecal metabolites (untargeted metabolomics), and colonic protein expression (Western blot) were assessed. Pyridoxic acid's effect on HT-29 cells was tested in vitro. Results: TFP significantly reduced DAI [2.0(1.8, 3.3) vs. 3.5(2.8, 4.5), P＜0.01], increased colon length [(7.2±1.1) vs. (5.5±0.5) cm, P＜0.05], lowered pathological score [6(3, 8) vs. 9(8, 10), P＜0.05], and decreased tumor number [2(1, 3) vs. 4(3, 4), P＜0.05] and volume [(11.02±7.88) vs. (24.99±3.38), P＜0.01]. Metagenomics revealed that TFP significantly reshaped gut microbiota (R²=0.173, P=0.027), enriching Candidatus Amulumruptor, Helicobacter, and Akkermansia. Metabolomics showed distinct profiles (R²=0.159, P=0.004), with pyridoxic acid elevated 1.20 fold (P＜0.001). Pyridoxic acid suppressed HT-29 cell viability and migration, and correlated positively with several upregulated bacteria, suggesting a microbiota-metabolite axis underlying its anti-tumor effect. TFP downregulated nuclear factor-κB (NF-κB) (P＜0.01) and upregulated phosphorylated AMP-activated protein kinase alpha (p-AMPKα) (P＜0.001), BAX (P＜0.001), and cleaved caspase-3 (P＜0.05). Conclusion: TFP inhibits colorectal cancer progression by modulating gut microbiota, elevating pyridoxic acid, suppressing NF-κB, and activating AMPK-mediated apoptosis.
Objective: To evaluate the prostate cancer (PCa) detection rates of targeted biopsy (TB) alone versus TB combined with systematic biopsy (SB) in patients with prostate imaging reporting and data systemv2.1 (PI-RADS v2.1) 4-5 lesions on biparametric magnetic resonance imaging. Methods: Clinical data were retrospectively collected from 1 060 patients who underwent combined prostate TB and SB at the First Affiliated Hospital of Nanjing Medical University between March 2018 and December 2023. All patients had pre-biopsy biparametric magnetic resonance imaging with PI-RADS v2.1 category 4 or 5 lesions. A comparative analysis was performed to evaluate the PCa detection rate and clinically significant prostate cancer (csPCa) detection rate between the two biopsy strategies. Using the postoperative pathological findings from 730 patients who underwent radical prostatectomy as the reference standard, a comparison of the pathological upgrading rates between TB alone and the combined biopsy approach was performed. Results: TB alone yielded detection rates of 79.6% (844/1 060) for PCa and 67.9% (720/1 060) for csPCa. The combined biopsy approach yielded detection rates of 82.2% (871/1 060) for PCa and 69.7% (739/1 060) for csPCa. The two strategies demonstrated no significant difference in detection rates of PCa and csPCa (P=0.136 and P=0.373) and showed substantial agreement (Kappa=0.918 for PCa and 0.958 for csPCa, both P＜0.001). This diagnostic alignment persisted across subgroups: among patients with PI-RADS category 4 lesions, the csPCa detection rates for TB alone and combined biopsy were 59.2% (395/667) and 61.5% (410/667), respectively, demonstrating high concordance (Kappa=0.953, P＜0.001). Among patients with PI-RADS category 5 lesions, the csPCa detection rates for TB alone and combined biopsy were 82.7% (325/393) and 83.7% (329/393), respectively, also demonstrating a high level of agreement (Kappa=0.964, P＜0.001). When compared with postoperative pathology, the overall pathological upgrading rates were 30.5% (223/730) for TB alone and 25.9% (189/730) for combined biopsy. The rates of upgrading specifically from biopsy-negative or ciPCa to csPCa were 12.3% (90/730) and 9.9% (72/730), respectively. Conclusion: For patients with PI-RADS 4-5 lesions, TB may serve as a clinically equivalent alternative to combined biopsy, achieving comparable diagnostic efficacy while reducing procedural burden on both patients and healthcare systems.
Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic significance, and assess its involvement in immune regulation. Methods: The expression, prognostic value, and correlation with tumor immunogenicity of CENPN in BRCA tissues were analyzed based on The Cancer Genome Atlas (TCGA) database. Verification was conducted using cancerous and adjacent normal tissues from BRCA patients who underwent surgical treatment at Yantai Mountain Hospital between January 2022 and April 2023. CENPN expression in various immune cells in the blood was examined using the Human Protein Atlas (HPA) database. Genetic alterations of CENPN in breast cancer tissues were analyzed via the cBioPortal database. CENPN-related genes were screened using the GEPIA 2.0 database, and the interaction network between CENPN and similar genes was visualized with the STRING database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the potential biological functions of CENPN. The correlation between CENPN expression and immune cell infiltration, as well as immune cell markers in BRCA tissues, was assessed using the TIMER 2.0 database. The effect of CENPN on the proliferation ability of breast cancer MCF-7 cells was detected by the CCK-8 assay, and its impact on the migration ability of MCF-7 cells was evaluated by a wound healing assay. Results: Analysis of TCGA database data revealed that CENPN expression was significantly higher in BRCA tissues compared to adjacent normal tissues (P＜0.05). Validation in our institutional cohort demonstrated a significantly higher positivity rate for CENPN in the 17 breast cancer tissues (82.4%) than in the paired paracancerous tissues (5.9%, P＜0.001). According to the HPA database, elevated CENPN expression was observed in T-reg cells, naïve B cells, and myeloid dendritic cells. Kaplan-Meier survival analysis indicated that patients with high CENPN expression had poorer overall survival (HR=1.39, P＜0.001), recurrence-free survival (HR=1.31, P＜0.001), post-progression survival (HR=1.28, P=0.036), and distant metastasis-free survival (HR=1.6, P＜0.001). Correlation analysis revealed a negative association between CENPN expression and tumor mutational burden in BRCA patients (r=-0.196, P＜0.001). Furthermore, CENPN expression was positively correlated with 5 out of 20 common immune checkpoint genes and negatively correlated with the remaining 15, suggesting its potential for predicting immunotherapy response. Analysis via the cBioPortal database showed that invasive lobular breast carcinoma had the highest CENPN alteration frequency, with amplification being the most common alteration in BRCA. Invasive mixed mucinous breast carcinoma exhibited the highest mutation frequency, and a key missense mutation (K329N) was identified as a potential driver in BRCA.GO enrichment analysis demonstrated that CENPN-related genes were primarily involved in cell cycle, DNA metabolic processes, cell division, nuclear lumen, chromosomes, nucleoplasm, and functions related to ATP, nucleotide, and small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in BRCA. Positive correlations were also found with markers for CD8+ T cells, B cells, T cells, and T-cell exhaustion.CCK-8 assay and wound healing experiments confirmed that CENPN knockdown significantly suppressed malignant phenotypes, including proliferation and migration, in MCF-7 cells. Additionally, CENPN knockdown was found to enhance the chemosensitivity of MCF-7 cells to the anti-tumor agents 5-fluorouracil and gemcitabine. Conclusion: CENPN serves as a potential prognostic biomarker and a novel target for immunotherapy in BRCA.
Objective: To evaluate the efficacy of different chemotherapy regimens in children with high-risk hepatoblastoma (HB). Methods: A retrospective cohort study was conducted on 99 patients under 18 years old with high-risk HB treated at Sun Yat-sen University Cancer Center between December 2004 and July 2024. The patients were divided into three groups: the PLADO regimen (cisplatin in combination with doxorubicin, n=27), the C5VD/IIV regimen (alternating cycles of cisplatin/5-flourouracil/vincristine/doxorubicin with irinotecan/ifosfamide/vincristine, n=29), and the modified SIOPEL-4 regimen (the original SIOPEL-4 regimen with omitted high-dose cisplatin on day15, n=43). Short-term efficacy, adverse effects, and long-term survival were compared among the three groups. Results: The objective response rates for the PLADO, C5VD/IIV, and modified SIOPEL-4 groups were 73.9% (17/23), 70.8% (17/24), and 88.6% (31/35), respectively, with no statistically significant difference among the three groups (P=0.190). The disease control rates were 82.6% (19/23), 83.3% (20/24), and 100.0% (35/35), the 3-year progression-free survival (PFS) rates were 19.2%, 37.0%, and 56.7%, and the 3-year overall survival (OS) rates were 69.2%, 55.6%, and 79.0%, respectively. The modified SIOPEL-4 group showed significantly better disease control rate and PFS rate compared withthe other two groups (both P＜0.05). After merging the PLADO and C5VD/IIV groups, the modified SIOPEL-4 group demonstrated significantly superior PFS and OS rates (both P＜0.05). Conclusions: The efficacy of modified SIOPEL-4 regimen in treating high-risk HB is superior compared with those of PLADO and C5VD/IIV regimens, but there remains room for further improvement in efficacy. Intensifying supportive care and pursuing aggressive local therapies, especially upfront liver transplantation for locally inoperable tumors, may further improve outcomes.
Objectives: To investigate the relationship between CD8+ tissue-resident memory T cells (TRM) and CD8+ bystander T cells (Tbys) in the tumor center (TC) and invasive margin (IM) regions of primary non-small cell lung cancer (NSCLC) and recurrence, and to perform stratified analysis based on lymph node status to guide individualized treatment. Methods: A retrospective review was conducted of patients with stage IA-IIIB non-small cell lung cancer (NSCLC) who underwent radical surgery at Shandong Provincial Cancer Hospital between January 1, 2014 and December 31, 2018. Tissue microarrays containing TC and IM regions were prepared, and multicolor immunofluorescence staining was applied to quantify the density of CD8+ T cells (CK- CD8+), tissue-resident memory T cells (CK- CD103+ CD8+), and bystander T cells (CK- CD103- CD8+). Kaplan-Meier and Cox proportional hazards models were used to identify factors associated with recurrence. Results: In the TC region, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys accounted for 34.3%, 67.9%, and 50.5% of CD8+ T cells, respectively. In the IM region, TRM/CD8+ T cells accounted for 29.6%, Tbys/CD8+ T cells for 70.7%, and TRM/Tbys for 41.9%. At a median follow-up of 37.9 months, recurrence occurred in 87 patients (34.0%). In all 256 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in both IM and TC regions were unrelated to RFS (all P＞0.05). Among the 172 N0 patients, the high Tbys/CD8+ T cell group in the IM region showed higher RFS rates than the low group (P=0.050), while the high-level groups for TRM/CD8+ T cells and TRM/Tbys in the TC region showed lower RFS rates than their low-level counterparts (all P＜0.05). Conversely, the high-level group for Tbys/CD8+ T cells in the TC region demonstrated a higher RFS rate than the low-level group (P=0.005). Multivariate Cox analysis revealed that high TC TRM/CD8+ T cells and high TC TRM/Tbys were independent risk factors for postoperative recurrence in N0 NSCLC patients (HR=2.772, 95% CI: 1.260-6.098; HR=2.656, 95% CI: 1.205-5.855), while high TC Tbys/CD8+ T cells was an independent protective factor for postoperative recurrence in N0 NSCLC patients (HR=0.324, 95% CI: 0.147-0.711). Among the 84 N1-2 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in the IM and TC regions were not associated with RFS (all P＞0.05). Conclusions: Specific CD8+ T cell subsets in the TC region of the primary tumor in NSCLC patients are associated only with recurrence after curative surgery in N0 patients. Elevated TRM/CD8+ T and TRM/Tbys ratios, coupled with reduced Tbys/CD8+ T ratios, correlate with heightened recurrence risk. This may aid in stratifying the risk of recurrence in N0 patients after surgery and guide treatment strategies.
Objective: To investigate the clinical value of dynamic monitoring of plasma circulating tumor DNA (ctDNA) in evaluating the efficacy of immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods: Plasma samples were collected at baseline and after every 2-3 treatment cycles from 94 patients with advanced ESCC receiving second-line sintilimab monotherapy in the ORIENT-2 study. Targeted sequencing was performed to analyze somatic variants in ctDNA, and the molecular tumor burden index (mTBI) was calculated to assess dynamic changes in ctDNA. Imaging examinations were conducted synchronously with plasma sample collection, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: A total of 614 somatic mutations were detected in 93 eligible baseline plasma samples, with a median of 6 mutations per sample. Missense mutations were the most frequent mutation type. The baseline mutational profile revealed frequently mutated genes including TP53 (82%), CDKN2B (23%), and NOTCH1 (22%). In the 68 patients with both baseline and post-2-cycle plasma samples, no significant changes were observed in the variant allele frequencies (VAFs) of core driver genes before and after treatment (all P＞0.05), and no newly emerged core driver gene mutations were identified. CCND1 copy number variation was associated with shorter progression-free survival (PFS) (HR=1.88, 95% CI: 1.08-3.27), while mutations in other genes, including TP53 and NOTCH1, showed no association with PFS (all P＞0.05). None of the frequently mutated genes were associated with overall survival (OS) (all P＞0.05). Among the 68 patients, 11 (15.9%) achieved ctDNA clearance, none of whom showed tumor progression on concurrent imaging evaluation. The remaining 57 patients had ctDNA that became positive or remained persistently positive, of whom 30 (52.6%) showed tumor progression on imaging, with a statistically significant difference between groups (P=0.002). Compared with patients whose ctDNA became or remained positive, those with ctDNA clearance exhibited significantly delayed tumor progression (HR=2.05, 95% CI: 1.06-3.96), but ctDNA status after 2 cycles did not significantly affect OS (HR=1.38, 95% CI: 0.62-3.09). After 2 cycles of treatment, patients in the low mTBI group had a higher disease control rate (DCR) than those in the high mTBI group [73.5% (25/34) vs. 38.2% (13/34), P=0.007], as well as superior PFS (HR=2.80, 95% CI: 1.65-4.75) and OS (HR=3.54, 95% CI: 1.95-6.42). Dynamic changes in mTBI were highly consistent with concurrent imaging response assessments. The molecular response group had a significantly higher DCR than the non-response group [87.5% (21/24) vs. 42.2% (19/45), P＜0.001], as well as superior PFS (HR=2.39, 95% CI: 1.41-4.06) and OS (HR=2.77, 95% CI: 1.46-5.22). Among 32 patients with stable disease (SD) at the first imaging evaluation after 2 cycles, those in the molecular response group had comparable PFS with the non-response group (HR=1.03, 95% CI: 0.51-2.08, P=0.942), but significantly longer OS (HR=3.12, 95% CI: 1.20-8.06). Conclusion: Dynamic monitoring of the ctDNA-based molecular tumor burden index (mTBI) provides real-time and sensitive molecular information for evaluating the efficacy of immunotherapy in advanced ESCC, demonstrating definite clinical value for personalized treatment management.
Objective: This study aims to investigate the expression characteristics of GLUT10 in breast cancer and its role in mediating cisplatin resistance, with the goal of providing a new molecular target for personalized breast cancer treatment. Methods: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were analyzed using the GEPIA2 platform to assess pan-cancer expression, while the UALCAN platform was used to analyze expression differences between breast cancer and normal breast tissues. In vitro, SK-BR-3 cells were divided into three groups: shScr (transfected with non-targeting scrambled shRNA), shSLC2A10#1, and shSLC2A10#2. MDA-MB-231 cells were divided into a vector control group and an SLC2A10 overexpression group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect SLC2A10 mRNA expression. Western blotting was used to detect GLUT10 and cleaved caspase-3 protein expression. The CM-H2DCFDA probe was used to measure intracellular reactive oxygen species (ROS) levels. Drug sensitivity and colony formation assays were performed to evaluate cisplatin sensitivity, and flow cytometry was used to detect apoptosis rates. Results: GEPIA2 analysis showed that GLUT10 expression was downregulated in adrenocortical carcinoma, cervical squamous cell carcinoma and adenocarcinoma, and kidney chromophobe tumor tissues compared to normal tissues, whereas it was upregulated in invasive breast cancer, glioma, skin melanoma, and thymoma. UALCAN analysis revealed that SLC2A10 mRNA levels in breast cancer tissues were 1.85-fold higher than in normal breast tissues (P＜0.001). RT-qPCR results showed that SLC2A10 mRNA expression levels in breast cancer cell lines, ranked from high to low, were Hs 578T (160.5±12.3), SK-BR-3 (115.2±10.5), MDA-MB-468 (50.1±5.2), T-47D (35.4±4.1), and MCF7 (25.6±3.8), all significantly higher than in normal breast epithelial cells (P＜0.001). In SK-BR-3 cells, compared with the shScr group, the shSLC2A10#1 and shSLC2A10#2 groups exhibited increased intracellular ROS levels (relative fluorescence intensity: 1.78±0.12 and 2.05±0.15, respectively; P＜0.05), increased cisplatin sensitivity, reduced colony numbers, and promoted cisplatin-induced ROS accumulation and apoptosis. In MDA-MB-231 cells, compared with the vector control group, the SLC2A10 overexpression group showed decreased intracellular ROS levels (relative fluorescence intensity: 0.58±0.09, P＜0.05), decreased cisplatin sensitivity, and inhibited cisplatin-induced ROS accumulation and apoptosis. Conclusion: GLUT10 is highly expressed in breast cancer and mediates cisplatin resistance by regulating ROS levels, suggesting it may serve as a novel therapeutic target for reversing drug resistance in breast cancer.
Objective: To compare the efficacy and safety of different-sized drug eluting beads preloaded with irinotrcan (DEBIRI) used in transarterial chemoembolization (TACE) as second-line therapy for colorectal cancer liver metastases (CRC-LM). Methods: A retrospective analysis was conducted on 65 patients with CRC-LM who received TACE at Yantai Yuhuangding Hospital from November 2020 to November 2022. All patients had progressed after first-line therapy. After excluding 5 lost-to-follow-up cases, 30 patients treated with 100-300 μm DEBIRI (small-size group) and 30 patients treated with 300-500 μm microspheres (large-size group) were included. Short- and long-term efficacy and adverse reactions were compared between the two groups. Univariate and multivariate Cox regression analyses were performed to identify factors influencing progression-free survival (PFS) and overall survival (OS). Results: In the small-size group, the objective response rates (ORR) at 1, 3, 6, and 12 months after treatment were 56.7%, 50.0%, 40.0%, and 30.0%, respectively, and the disease control rates (DCR) were 93.3%, 90.0%, 80.0%, and 66.7%, respectively. In the large-size group, the ORR at the same time points were 36.7%, 26.7%, 23.3%, and 16.7%, respectively, and the DCR were 86.7%, 76.7%, 76.7%, and 60.0%, respectively. None of the differences between the two groups were statistically significant (all P＞0.05). The median PFS and OS in the small-size group were 15.0 and 26.0 months, respectively, while in the large-size group they were 13.8 and 21.5 months, respectively, with no statistically significant differences between groups (all P＞0.05). The overall incidence of adverse reactions was 76.6% in the small-size group and 70.0% in the large-size group (P=0.559). The incidence of grade ≥3 adverse reactions was 23.3% and 16.7%, respectively (P=0.519). No treatment-related deaths occurred in either group. Multivariate Cox regression analysis showed that Child-Pugh grade, Eastern Cooperative Oncology Group (ECOG) score, and number of liver metastases were independent influencing factors for both PFS and OS. Conclusion: There was no significant difference in efficacy between 100-300 μm and 300-500 μm drug eluting beads preloaded with irinotrcanused in TACE for the treatment of CRC-LM, and both demonstrated good safety profiles.
Anaplastic lymphoma kinase (ALK) fusion gene is one of the most common driver genes in non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (TKIs) have become the standard treatment option for patients with advanced ALK gene fusion positive NSCLC. Currently, the China National Medical Products Administration (NMPA) has approved ten ALK-TKIs, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, envonalkib, dirozalkib and conteltinib. Iruplinalkib is a novel ALK-TKI independently developed in China. On June 27, 2023, the NMPA approved iruplinalkib for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who had progressed on or were intolerant to crizotinib. On January 16, 2024, the NMPA approved iruplinalkib for first-line treatment of patients with locally advanced or metastatic ALK-positive NSCLC patients. To help clinicians better understand the efficacy and safety of iruplinalkib and to facilitate its more rational clinical application, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists organized experts to develop the "Expert consensus on iruplinalkib for the treatment of ALK-positive non-small cell lung cancer (2026 edition)". This consensus provides systematic and comprehensive update of clinical research data on iruplinalkib published before June 25, 2026, based on the 2024 edition. It covers common clinical issues and provides corresponding recommendations for the use of iruplinalkib in the treatment of ALK-positive NSCLC.
Objective: To analyze the clinical characteristics of breast cancer susceptibility gene (BRCA) germline mutation carriers with ovarian cancer, collect family history information, screen for potential BRCA mutation carriers among family members, and provide preventive guidance for high-risk populations of ovarian cancer. Methods: A total of 77 patients with ovarian cancer (including fallopian tube cancer and primary peritoneal cancer, hereinafter collectively referred to as ovarian cancer) who were treated at the Department of Obstetrics and Gynecology, Chinese PLA General Hospital between 2015 and 2024 and confirmed to carry germline mutations in the BRCA1/2 genes through genetic testing were selected. According to the test results, they were divided into the BRCA1 mutation group (48 cases) and the BRCA2 mutation group (29 cases). The clinical baseline data, pathological characteristics, treatment efficacy, and survival outcomes were compared between the two groups. Family history information was collected, and BRCA genetic testing was performed on 81 relatives from 37 families. Family characteristics were analyzed in combination with family history and genetic testing results, and preventive guidance was provided to high-risk populations. Results: The age at onset of the 77 patients ranged from 19 to 78 years, with a median age of 55 years. The age at onset in the BRCA1 mutation group ranged from 19 to 74 years, with a median age of 52 years, which was earlier than the median age of 56 years in the BRCA2 mutation group. 43.8% (21/48) of BRCA1 carriers had a family history of hereditary breast and ovarian cancer syndrome (HBOC), which was 1.5 times higher than that in the BRCA2 group (17.2%, 5/29, P＜0.05). There were no statistically significant differences in fertility status, body mass index (BMI), personal history of breast cancer, and pre-treatment carbohydrate antigen 125 (CA125) levels between the two groups (P＞0.05). The median progression-free survival (PFS) for initial treatment was 21.8 months in BRCA1 mutation patients and 20.7 months in BRCA2 mutation patients. Among the 81 relatives, 47 BRCA gene mutation carriers were detected, of whom 63.8% (30/47) were from families without a family history of HBOC. Among 31 female mutation carriers, only 2 underwent risk-reducing salpingo-oophorectomy (RRSO). A survey of the general population showed that 78.5% of non-carrier women would accept prophylactic surgery, while the average surgical intention score among carriers was only 2.6 (on a 5-point scale), with 75.0% preferring to delay RRSO until after natural menopause. Conclusions: Chinese BRCA1/2 mutation carriers have significant concerns regarding iatrogenic menopause caused by RRSO, creating a decision-making dilemma for surgical prevention of ovarian cancer in high-risk populations. The age at onset of ovarian cancer in Chinese BRCA1/2 mutation carriers is relatively late compared with international data, and the optimal timing of surgery for Chinese women still requires further investigation. Developing a localized surgical timing prediction model may help advance ovarian cancer prevention and treatment efforts.
Objective: To investigate the quality of life (QoL) and its influencing factors in patients with early-stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. Methods: A total of 134 patients with EC or AEH who received fertility-sparing treatment at Peking Union Medical College Hospital between August 2023 and December 2024 were enrolled. Patients were divided into two treatment groups: those receiving gonadotropin-releasing hormone agonist (GnRHa) combined with aromatase inhibitors, and those receiving high-dose oral progestins. During treatment, diagnostic curettage or hysteroscopy was performed every 3 months, and treatment was discontinued upon assessment of complete response (CR). According to treatment duration (time to achieve CR), patients were categorized into the 3-month group (n=79), 6-month group (n=40), and ≥9-month group (n=15). The Functional Assessment of Cancer Therapy-General (FACT-G) version 4 was used to quantitatively assess QoL during treatment; questionnaires were administered every 3 months, and all 134 patients completed the survey at baseline and at 3, 6, and 9 months of treatment. Multivariate linear regression analysis was used to analyzed the influencing factors of QoL. Results: Among the 134 patients, 61 (45.5%) had AEH and 73 (54.5%) had EC; 71 patients (53.0%) received GnRHa combined with aromatase inhibitors, and 63 (47.0%) received high-dose oral progestins. QoL assessment showed that FACT-G scores gradually increased from baseline in the 3-month and 6-month groups, indicating improvement in QoL as treatment progressed; whereas the median FACT-G scores in the ≥9-month group remained below 80 throughout treatment, indicating relatively lower QoL. However, there was no statistically significant difference in FACT-G scores at CR among the 3-month, 6-month, and ≥9-month groups (median scores: 82.0, 83.0, and 76.5, respectively; H=1.575, P=0.455). Univariate analysis showed no significant differences in FACT-G scores at CR among patients with different treatment regimens, body mass index (BMI), treatment duration, pathological type, marital status, treatment history, or reproductive history (all P＞0.05). Multivariate analysis showed that FACT-G scores at CR were positively correlated with baseline FACT-G scores (B=0.634, P＜0.001) and negatively correlated with BMI (B=-4.021, P=0.035). No correlation was observed between treatment regimen and QoL. Conclusions: In fertility-sparing treatment, BMI may be a key factor affecting QoL, while long-term treatment may lead to a decline in QoL. Clinical attention should be paid to weight management and psychosocial support.
Objective: To investigate the short-term efficacy and safety of neoadjuvant immunotherapy in patients with locally advanced colon cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H). Methods: A retrospective analysis was conducted on the clinicopathological data of 21 patients with dMMR/MSI-H locally advanced colon cancer who received neoadjuvant immunotherapy followed by radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences between February 2023 and December 2025. The short-term efficacy and safety of neoadjuvant immunotherapy and subsequent radical surgery were evaluated. Results: Among the 21 patients, there were 15 male and 6 female, with a median age of 54 years (range, 33 to 79 years). Ten patients had ascending colon cancer, six had sigmoid colon cancer, four had transverse colon cancer, and one had descending colon cancer. No grade 4 or higher immune-related adverse events (irAEs) occurred in any patient after neoadjuvant immunotherapy. Grade 1 to 2 irAEs were occurred in 8 patients (38.1%, 8/21), and only 1 patient (4.8%, 1/21) developed grade 3 irAE. All patients underwent radical surgery after neoadjuvant immunotherapy, with R0 resection rate of 100.0% (21/21). No patient developed grade Ⅲ or higher postoperative complications. Only four patients (19.0%, 4/21) develpoed grade Ⅰ to Ⅱ postoperative complications, including anastomotic leakage in one patient (4.8%, 1/21), paralytic intestinal obstruction in 1 patient (4.8%, 1/21), intra-abdominal infection in 1 patient (4.8%, 1/21), and fever in 1 patient (4.8%, 1/21). Postoperative pathological results showed that all patients achieved tumor downstaging compared with the clinical stage before neoadjuvant therapy. Sixteen patients (76.2%, 16/21) achieved pathological complete response (pCR), and 18 patients (85.7%, 18/21) achieved major pathological response (MPR). With a median follow-up of 12 months (range, 3 to 37 months), no patient developed local recurrence or distant metastasis. Conclusion: For patients with dMMR/MSI-H locally advanced colon cancer, preoperative neoadjuvant immunotherapy can achieve remarkable efficacy without increasing the risk of postoperative complications, representing a safe and effective therapeutic strategy.
Objective: To investigate the density, distribution and clinicopathological significance of S100+ dendritic cells, FoxP3+ regulatory T cells and mature tertiary lymphoid structures (TLS) in micronodular thymic tumors with lymphoid stromal hyperplasia (MNN). Methods: The clinicopathological data of 28 patients with MNN admitted to Nanjing Chest Hospital, Jiangsu Province Hospital and Jiangsu Cancer Hospital from August 2016 to August 2024 were retrospectively collected. The clinical and imaging features, pathological characteristics, immunophenotype, immune microenvironment and molecular characteristics of the patients were analyzed. Result: Among the 28 cases of MNN, 18 were micronodular thymoma with lymphoid stromal hyperplasia (MNT), and 10 were micronodular thymic carcinoma with lymphoid stromal hyperplasia (MNC). Both exhibited characteristic lymphoid stromal surrounding the tumor with a nodular growth pattern. Immunohistochemistry showed that MNT was characterized by CD5-/CD117-/Glut1-/TdT+/low Ki-67 expression while MNC was characterized by CD5+/CD117+/Glut1+/TdT- (or occasional TdT+), and high Ki-67 expression. The expression level of S100+ dendritic cells in MNT [(1 765±733) cells/mm2] was higher than that in MNC [(693±129) cells/mm2, P＜0.05], whereas the number of FoxP3+ regulatory T cells in MNT [(285±100) cells/mm2] was lower than that in MNC [(711±177) cells/mm2, P＜0.05]. The density of mature TLS in MNC [(28±17)/10 low-power field (LPF)] was significantly higher than that in MNT [(3.4±2.6)/10 LFP, P＜0.001)]. First-generation sequencing results revealed GTF2I mutations in two MNT cases, whereas no such mutations were detected in seven MNC cases. All 28 cases of MNN underwent resection of mediastinal tumors, and four received postoperative radiotherapy. The follow-up period ranged from 6 to 96 months (one patient was lost to follow-up), with a median follow-up of 48 months. None of the 27 patients experienced recurrence or metastasis. Conclusions: Both MNT and MNC share similar morphological characteristics. The immunophenotype CD5+/CD117+/Glut1+/TdT- and high Ki-67 index can effectively distinguish MNC. The overall prognosis of MNN is favorable. S100+ dendritic cells, FoxP3+ regulatory T cells, mature TLS, and GTF2I genes alterations are associated with the prognosis of this disease and hold significant value in its diagnosis and differential diagnosis.
Objective: To investigate the feasibility and safety of interventional embolization combined with robotic surgery for adrenal pheochromocytoma. Methods: A retrospective analysis was conducted on clinical data from three patients with adrenal pheochromocytoma who underwent interventional embolization combined with robotic surgery at Tianjin First Central Hospital from June 2022 to March 2024. All patients underwent preoperative adrenal artery embolization followed by robot-assisted laparoscopic adrenalectomy. Clinical data including operative time, intraoperative blood loss, postoperative drainage tube duration, postoperative hospital stay, pathological findings, and follow-up results were collected. Focusing on its impact on maintaining perioperative (particularly intraoperative) hemodynamic stability, and to evaluate its effect on reducing intraoperative blood loss. Results: Among the three patients, one was male and two were female, with ages of 50, 76, and 46 years, respectively. Pheochromocytomas were located on the left side in two cases and on the right side in one case. The maximum tumor diameters were 6.0 cm, 6.2 cm, and 5.8 cm, respectively. All three procedures were successful without conversion to open surgery. The operative times were 117, 181, and 127 minutes, respectively. Intraoperative blood loss was 100 ml, 50 ml, and 30 ml, respectively, with no intraoperative blood transfusion required. Postoperative drainage tube durations were 4, 4, and 3 days, respectively. Postoperative hospital stays were 7, 6, and 6 days, respectively. One patient experienced a hypertensive episode after embolization, while the other two experienced hypertensive episodes during embolization, all of which were controlled with medication. During robotic surgery, all three patients maintained stable blood pressure, and no other surgery-related complications were observed. Complete resection of the adrenal tumors was achieved in all cases. During robotic surgery, a significant reduction in adrenal blood supply was noted. Postoperatively, two patients developed hypotension, which stabilized after norepinephrine infusion. Follow-up ranged from 10 to 30 months, with a median follow-up of 22 months. All patients maintained stable blood pressure levels, with no tumor recurrence or complications observed. Conclusions: Preoperative interventional embolization combined with robot-assisted surgery for pheochromocytoma is safe and feasible. It contributes to maintaining intraoperative hemodynamic stability while reducing tumor blood supply, thereby decreasing perioperative blood loss and potentially lowering surgical difficulty.
Objective: To explore the clinical characteristics and prognosis of patients with thyroid cancer complicated by connective tissue disease. Methods: A retrospective analysis was conducted on the clinical data of 70 patients with thyroid cancer complicated by connective tissue disease who were admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from May 30, 2006, to April 30, 2024 and telephone follow-up was performed. Results: Among the 70 patients with thyroid cancer complicated by connective tissue disease, 68 cases (97.1%, 68/70) had papillary thyroid carcinoma, and 2 (2.9%, 2/70) had medullary thyroid carcinoma; 67 cases (95.7%, 67/70) were female. The age at diagnosis of thyroid cancer was (48.73±11.74) years, and the median interval from connective tissue disease diagnosis to thyroid cancer diagnosis was 7 years (range, 3 to 12 years). Among them, there were 29 cases (41.4%, 29/70) of rheumatoid arthritis, 24 cases (34.3%, 24/70) of Sjögren's syndrome, 12 cases (17.1%, 12/70) of systemic lupus erythematosus, 3 cases (4.3%, 3/70) of systemic sclerosis, and 2 cases (2.9%, 2/70) of dermatomyositis. The stages of thyroid cancer were stage Ⅰ in 55 cases (78.6%, 55/70), stage Ⅱ in 11 cases (15.7%, 11/70), stage Ⅲ in 1 case (1.4%, 1/70), and unknown in 3 cases (4.3%, 3/70). Multifocality was observed in 37 cases (52.9%,37/70), capsular invasion in 46 (65.7%,46/70) cases, perineural invasion in 1 (1.4%,1/70) case, and lymphovascular invasion in 3 (4.3%,3/70) cases. The median follow-up time was 73.50 months (range, 20.9 to 235.0 months). Six patients were lost to follow-up, one patient died of COVID-19 and the remaining 63 patients (98.4%, 63/64) did not experience recurrence or metastasis. Conclusions: Patients with thyroid cancer complicated by connective tissue disease are mostly female, and the predominant pathological type is papillary thyroid carcinoma. Most patients are diagnosed at an early stage. No recurrence or metastasis was observed during follow-up,and further confirmation by large-sample studies is needed.
Objective: To investigate the effects of early postoperative enteral nutrition on nutritional status, immune function, and postoperative recovery in breast cancer patients receiving neoadjuvant therapy. Methods: A total of 90 breast cancer patients who underwent neoadjuvant therapy at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2024 to May 2025 were enrolled. A randomized controlled study design was adopted, and the patients were divided into a control group (n=45) and a study group (n=45) using a random number table method. The perioperative diet for both groups followed the nutritional principles of adequate energy, high protein, high vitamins, and low fat, ensuring a daily caloric intake of approximately 2 000 kcal per person. Patients in the study group additionally received an oral special medical purpose formula food for tumor nutrition. Nutritional intervention in both groups started on the first day after surgery and continued until the seventh day after surgery. Nutritional indicators, immune function parameters, and surgery-related complications were compared between the two groups before and after intervention. Results: Baseline characteristics were balanced between the study group and the control group. There were no statistically significant differences between the two groups in age, body mass index, Nutritional Risk Screening 2002 score, pathological type, or disease stage (all P＞0.05). Before the intervention, there were also no statistically significant differences in nutritional indicators (serum total protein, serum albumin) or immune function parameters (T lymphocyte subsets CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺ratio, immunoglobulins IgA, IgG, IgM) between the two groups (all P＞0.05). After the intervention, the nutritional indicator levels in the study group were significantly higher than those in the control group: serum total protein was (72.42±3.61) g/L vs (70.74±3.76) g/L (t=2.040, P=0.045); serum albumin was (42.96±2.20) g/L vs (42.02±1.97) g/L (t=2.027, P=0.046). Additionally, some immune function parameters in the study group were also better than those in the control group: CD3⁺ was 75.41%±7.72% vs 69.26%±8.55% (t=2.814, P=0.007); CD8⁺ was 31.39%±9.43% vs 26.30%±6.89% (t=2.230, P=0.030); the levels of IgA, IgG, and IgM in the study group were also significantly higher than those in the control group (all P＜0.05). In terms of postoperative recovery, the drainage tube removal time in the study group was significantly shorter than that in the control group [(17.05±5.65) days vs (19.59±5.54) days; t=-2.029, P=0.046]. The suture removal time and incidence of poor wound healing were also lower in the study group than in the control group, but the differences were not statistically significant (both P＞0.05). Conclusion: Early postoperative enteral nutrition support can effectively improve the nutritional status of breast cancer patients after neoadjuvant chemotherapy, enhance immune function to a certain extent, and promote postoperative recovery.
Objective: To comprehensively evaluate homologous recombination deficiency (HRD) status via next-generation sequencing (NGS) in ovarian cancer patients and analyze its correlations with clinicopathological features, microsatellite instability (MSI), and tumor mutational burden (TMB), thereby providing evidence for genetic risk assessment, PARP inhibitor (PARPi)-targeted therapy, and prognostic management. Methods: A total of 182 ovarian cancer patients who underwent HRD testing in our department between January 2021 and August 2025 were enrolled. NGS was employed to detect germline and somatic mutations in BRCA1/2 and other genes, HRD scores, MSI, and TMB. HRD positivity was defined as the presence of a BRCA1/2 pathogenic/likely pathogenic mutation and/or a positive HRD score. Immunohistochemistry (IHC) was used to assess the expression of mismatch repair (MMR) protein and p53. Results: The overall HRD-positive rate was 65.38% (119/182), with an HRD score-positive rate of 53.30%. High-grade serous carcinoma (HGSC) constituted 84.62% (154/182) of cases and exhibited a significantly higher HRD-positive rate than those of other rare pathological subtypes [75.97% (117/154) vs. 7.14% (2/28), P＜0.001]. The BRCA mutation rate was 36.81% (67/182), with germline BRCA mutations accounting for 21.98% (40/182). Within the 119 HRD-positive patients, 56.30% harbored a BRCA mutation, 81.51% were HRD score-positive, and 43.70% were BRCA wild-type but HRD score-positive. Among other homologous recombination repair (HRR) genes, RAD51D had the highest mutation rate (12.64%, 23/182). A high concordance rate of 95.60% (174/182) was observed between p53 IHC results and TP53 mutational status, which reached 96.10% (148/154) in HGSC patients. In 167 patients, only one patient (0.60%) exhibited both MSI-high (H) and TMB-H, carrying a BRCA2 mutation and was HRD score-positive. TMB-H status was significantly associated with HRD positivity (P＜0.05), whereas no significant correlation was found between MSI status and HRD (P＞0.05). Conclusions: NGS enables a comprehensive and integrated assessment of HRD status in ovarian cancer. Our cohort revealed a high HRD-positive rate, particularly in HGSC. A substantial proportion of patients without BRCA mutations exhibited genomic instability, suggesting potential benefit from PARPi therapy. The correlation between HRD status and TMB features provides a rationale for exploring combination immunotherapy strategies.
Compared with postmenopausal patients, premenopausal patients with hormone receptor-positive (HR+) breast cancer generally exhibit higher tumor heterogeneity, greater invasiveness and a poorer prognosis, with a 5-year postoperative recurrence rate of 20%-30%. Endocrine therapy based on ovarian function suppression (OFS) is a key strategy to reduce the risk of recurrence, and gonadotropin-releasing hormone agonists (GnRHa) are commonly used agents for OFS in clinical practice. GnRHa combined with endocrine therapy has become the standard treatment regimen for intermediate- and high-risk premenopausal patients with HR+ breast cancer. The recommended treatment duration is 5 years, and extended treatment may be considered in selected high-risk patients. However, long-term GnRHa use (2-5 years or >5 years) may lead to decreased treatment adherence or increased adverse events, thereby potentially affecting patient prognosis. Furthermore, there is still a lack of standardization regarding the appropriate patient population for GnRHa use beyond 5 years, long-term management strategies, and drug switching approaches. To address these issues, the Committee of Breast Cancer Society of Chinese Anti-Cancer Association and other organizations convened a panel of experts to develop this consensus based on domestic and international evidence-based medical evidence and clinical practice in China, following the Delphi method. This consensus aims to standardize the long-term application and management of GnRHa, provide a reference for clinicians, help patients complete the planned treatment courses, and ultimately improve patients' quality of life and long-term prognosis.
