Third-line treatment for metastatic colorectal cancer(mCRC)refers to subsequent therapeutic interventions following the failure or intolerance of first-and second-line treatments.This represents a critical challenge in clinical practice and a core focus of translational medicine research in recent years.With advancements in molecular typing technologies and the emergence of novel therapies,the third-line treatment strategy has evolved from traditional chemotherapy toward precision targeting and immunotherapy.A comprehensive literature search was conducted across PubMed,ClinicalTrials.gov database and American Society of Clinical Oncology(ASCO),European Society for Medical Oncology(ESMO)conference abstracts.Phase Ⅲ randomized controlled trials,phase Ⅰ/Ⅱ frontier clinical studies,and authoritative reviews were included,with an emphasis on data related to survival benefits,drug resistance mechanisms,and biomarkers.This review provided an in-depth analysis of significant progress in third-line treatment strategies for mCRC,encompassing standard therapies[regorafenib,fruquintinib,trifluridine/tipiracil,anti-epidermal growth factor receptor(EGFR)rechallenge therapy],targeted therapies(e.g.,BRAF V600E inhibitors,ERBB2 amplification inhibitors,KRAS G12C inhibitors)and immunotherapies[microsatellite instability-high(MSI-H)/deficient mismatch repair(dMMR),microsatellite stable(MSS)/proficient mismatch repair(pMMR)and target-immune combination therapies].Notable breakthroughs have been achieved in targeted therapies.Anti-EGFR rechallenge therapy extended the median overall survival(OS)to 17.3 months in RAS/BRAF wild-type patients identified through dynamic circulating tumor DNA(ctDNA)monitoring.However,drug resistance remains complex,with high secondary mutation rates necessitating further optimization of dynamic monitoring systems.For BRAF V600E mutations,triple therapy(encorafenib+binimetinib+cetuximab)demonstrated a median OS of 9.3 months[hazard ratio(HR)=0.52],surpassing conventional treatments.The combination of KRAS G12C inhibitor adagrasib with cetuximab achieved an objective response rate(ORR)of 34%and a median OS of 15.9 months,though tumor resistance continued to pose challenges.In the realm of immunotherapy,dual immunotherapy(nivolumab+ipilimumab)yielded a 4-year OS rate of 71%in MSI-H/dMMR patients.For MSS patients,immune-targeted combination strategies(e.g.,cabozantinib+atezolizumab)increased the ORR to 27.6%.Emerging therapies include artificial intelligence platforms for precision medicine,gut microbiota-based biomarkers and fecal microbiota transplantation,as well as advancements in chimeric antigen receptor-T(CAR-T)cell therapy.By summarizing the current status and progress of third-line treatment for mCRC,this review aims to inform clinical decision-making and guide future research directions.

Approximately two-thirds of patients with head and neck squamous cell carcinoma present with locally advanced disease at the time of consultation.Even with the multidisciplinary team(MDT)diagnosis and treatment model,their treatment outcomes still need improvement.Immunotherapy has become the standard treatment for recurrent and metastatic head and neck squamous cell carcinoma.In recent years,it has achieved initial success in clinical studies on locally advanced diseases,especially in the perioperative period,but its application in other treatment fields still faces many problems.The Head and Neck Cancer Committee of Chinese Society of Clinical Oncology organized experts to form 14 consensus opinions through multiple rounds of discussions informed by evidence-based medical evidence and clinical practice.Thess consensus statements were finally formulated,comprehensively covering the entire management of immunotherapy for locally advanced head and neck squamous cell carcinoma,summarized as follows:① Regarding the whole-course treatment strategy,for patients with locally advanced head and neck squamous cell carcinoma undergoing radical surgery followed by adjuvant chemoradiotherapy,a comprehensive treatment approach combining neoadjuvant immunotherapy,immunotherapy combined with chemoradiotherapy,and adjuvant immunotherapy is recommended.② In the neoadjuvant treatment phase,for patients requiring neoadjuvant immunotherapy,the combination of immunotherapy with chemotherapy is recommended,with a course of 2-3 cycles.For non-oral cancer patients who achieve radiological tumor response after neoadjuvant treatment and require organ preservation,definitive radiotherapy should be administered.③ The immunotherapy combined with radiotherapy phase remains controversial,and the optimal treatment regimen and patient selection criteria require further clinical investigation.④ In the adjuvant immunotherapy phase,for locally advanced head and neck squamous cell carcinoma patients with high-risk factors,the combination of adjuvant radiotherapy with immunotherapy is recommended postoperatively,with a course of adjuvant immunotherapy ranging from 6 to 12 months.Corresponding recommendation levels for different treatment scenarios are obtained through voting.This consensus will help guide the standardized application of immunotherapy for locally advanced head and neck squamous cell carcinoma,lay the foundation for further clinical research,and strive to promote the research level of immunotherapy for locally advanced head and neck squamous cell carcinoma in China.This consensus has been registered on the Practice guideline REgistration for transPAREncy(PREPARE)platform,with the registration number PREPARE-2025CN1241.

Background and purpose:Patients with prostate cancer(PCa)have consistently shown suboptimal responses to immunotherapy,which may be closely related to the immunosuppressive state of the PCa tumor microenvironment.MYC,a key transcription factor in cancer cells,is involved in cell proliferation,differentiation,apoptosis and immune surveillance by regulating the expression of intracellular genes.This study aimed to elucidate the mechanisms through which MYC fosters an immunosuppressive state within the PCa tumor microenvironment and to delineate its functional impact on PCa cells.Methods:We performed clustering and annotation of single-cell RNA sequencing(scRNA-seq)data from PCa,and conducted subcluster analyses for tumor cells,T cells,and macrophages respectively.The expression changes of MYC and CD47 across tumor subtype were analyzed,and the expression variations of signal regulatory protein alpha(SIRPα)among macrophage subtype were assessed.Furthermore,we divided the PCa transcriptomic dataset samples into high-and low-MYC expression groups based on MYC expression levels,and performed differential expression analysis and enrichment analysis for each group.The functional role of MYC in PCa cells was validated using chromatin immunoprecipitation-quantitative polymerase chain reaction(ChIP-qPCR)and experimental analyses.Furthermore,animal experiments(reviewed and approved by the ethics committee of the First Affiliated Hospital of Henan University of Science and Technology,approval number:D-2025-B015)were conducted to further validate the relationship between MYC and CD47.Finally,we analyzed and validated the whey acidic protein four-disulfide core domain 2(WFDC2)+tumor subtype using transcriptomic data from PCa.Results:Through the analysis of scRNA-seq data from PCa,a total of 32,977 cells were identified,and 7 distinct cell types were annotated.The tumor cells were further divided into 10 tumor cell subtypes,among which the WFDC2+tumor cell subtype exhibited more intensive cellular communication with CD8+T cells and macrophages within the PCa tumor microenvironment.MYC and CD47 exhibited high expression levels during the middle-to-late stages of differentiation in PCa cells,whereas SIRPα maintained high expression throughout the macrophage differentiation trajectory.Enrichment analysis revealed that the WFDC2+tumor cell subtype was primarily enriched in signaling pathways such as transforming growth factor-β(TGF-β)and Wnt/β-catenin.ChIP-qPCR confirmed the regulatory relationship between MYC and CD47 expression.Additionally,it was found that MYC knockdown significantly inhibited the proliferation and invasion abilities of PCa cells,while overexpression of CD47 could reverse this effect.Animal experiment results confirmed an positive correlation between MYC and CD47 protein expression.Furthermore,Tumor Immune Dysfunction and Exclusion(TIDE)and Estimate analyses indicated that patients in the low-expression group of the WFDC2+tumor cell subtype exhibited a potentially better response to immunotherapy compared to those in the high-expression group.Conclusion:The findings of this study elucidate the role of MYC in the PCa tumor immune microenvironment.Specifically,MYC promotes the proliferation and migration of PCa cells by regulating the expression of CD47.These insights provide novel perspectives for the treatment of PCa patients.

Background and purpose:Breast cancer stem cells play an important role in the occurrence and development of cancer.The high mortality of breast cancer patients is closely related to the recurrence and metastasis of cancer.However,the self-renewal and differentiation ability of breast cancer stem cells can lead to chemotherapy resistance,thus affecting the recurrence and metastasis of cancer.This study aimed to explore the impact of miR-193a-3p on the migration and invasion of breast cancer stem cells by targeting the tripartite motif-containing protein 14(TRIM14).Methods:Human breast cancer cell T47D was randomly assigned into control group,NC mimics group(transfected with NC mimics),miR-193a-3p mimics group(transfected with miR-193a-3p mimics),miR-193a-3p mimics+pcDNA-NC group(transfected with miR-193a-3p mimics+pcDNA-NC)and miR-193a-3p mimics+pcDNA-TRIM14 group(transfected with miR-193a-3p mimics+pcDNA-TRIM14).Separation of stem cells using flow cytometry and detection of cell spheroidization ability were carried out.Cell counting kit-8(CCK-8)experiment was used to detect cell proliferation.Transwell experiment was used to measure cell migration and invasion.Flow cytometry was used to detect cell apoptotic rate.Western blot was used to detect the expressions of cyclin D1,matrix metalloproteinase-2(MMP-2),Bcl-2-associated X protein(Bax),and TRIM14 protein in cells.Dual luciferase assay was used to detect the interaction between miR-193a-3p and TRIM14.Results:T47D stem cells had the ability to form spheroids,and with increasing time,the spheroid volume of T47D stem cells gradually increased.Compared with the Control group and NC mimics group,the miR-193a-3p mimics group showed increased miR-193a-3p expression,apoptotic rate,and Bax protein expression(P＜0.05),and decreased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).Compared with the miR-193a-3p mimics group and the miR-193a-3p mimics+pcDNA NC group,the miR-193a-3p mimics+pcDNA-TRIM14 group showed decreased cell apoptosis rate and Bax protein(P＜0.05),and increased TRIM14 mRNA and protein expression,survival rate,clone number,migration number,invasion number,cyclin D1 and MMP-2(P＜0.05).There were multiple binding sites between miR-193a-3p and TRIM14.Compared with the miR-NC+TRIM14-WT group,the miR-193a-3p mimics+TRIM14-WT group showed a prominent decrease in dual luciferase activity(P＜0.05).Conclusion:MiR-193a-3p may inhibit the migration and invasion of breast cancer stem cells through inhibiting TRIM14.

Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.

Background and purpose:Colorectal cancer(CRC),ranking as the third most common malignant tumor globally,continues to pose a significant public health challenge due to its high incidence and mortality rates.Chemotherapy remains a cornerstone treatment for advanced CRC.However,its efficacy is often severely limited by the emergence of multidrug resistance(MDR).The drug efflux mediated by ABCB1 is a key mechanism underlying chemotherapeutic failure.Although the non-steroidal anti-inflammatory drug tepoxalin exhibits potential antitumor activity,it remains unclear whether it influences CRC progression and chemoresistance by targeting ABCB1.This study aimed to elucidate the mechanism by which tepoxalin suppresses CRC cell growth and reverses chemoresistance through the regulation of ABCB1.Methods:This study employed a multifaceted research strategy:Bioinformatics analysis was conducted using the DepMap,The Cancer Genome Atlas(TCGA),Genotype-Tissue Expression(GTEx)and Human Protein Atlas(HPA)databases to analyze ABCB1 expression profiles and drug sensitivity.In vitro,the cell counting kit-8(CCK-8)assay was used to assess cell proliferation and chemosensitivity,and IC50 values were calculated.A subcutaneous xenograft model in nude mice was established to evaluate the antitumor efficacy in vivo.The drug affinity responsive target stability(DARTS)assay was performed to validate the direct binding between tepoxalin and ABCB1 protein.Transcriptome sequencing and gene set enrichment analysis(GSEA)were utilized to identify downstream signaling pathways.Western blot and immunohistochemistry were applied to detect the expression changes of key proteins.The PI3K-Akt pathway inhibitor copanlisib was used for reverse validation.Statistical analysis was performed using SPSS 20.0 software,and graphs were generated using GraphPad Prism 8.0.1.A value of P＜0.05 was considered statistically significant.Results:ABCB1 was significantly overexpressed in CRC tissues and cell lines(P＜0.05).Cells with high ABCB1 expression exhibited increased sensitivity to tepoxalin(R=-0.323,P＜0.001).Tepoxalin directly bound to the ABCB1 protein and promoted its proteasomal degradation.In vivo,tepoxalin significantly inhibited the growth of xenograft tumors(P＜0.01)and downregulated the expression of ABCB1 and Ki-67 proliferation index in tumor tissues.Transcriptomic analysis revealed that tepoxalin suppressed the PI3K-Akt signaling pathway[GSEA,false discovery rate(FDR)＜0.05],leading to reduced transcriptional expression of ABCB1.This effect was replicated using the PI3K-Akt pathway inhibitor copanlisib.Ultimately,tepoxalin synergistically enhanced the efficacy of 5-fluorouracil(5-FU)through the aforementioned actions.Conclusion:Tepoxalin targets ABCB1 through a dual-track mechanism:it directly binds to and destabilizes the ABCB1 protein while simultaneously downregulating its transcriptional expression via inhibition of the PI3K-Akt pathway.This coordinated action can synergistically inhibit CRC cell growth and effectively reverse chemoresistance,offering a novel potential therapeutic strategy for overcoming drug resistance in CRC.

Background and purpose:In recent years,chimeric antigen receptor T(CAR-T)cell therapy has achieved breakthrough progress in cancer treatment.γδ T cells,with their non-major histocompatibility complex(MHC)-restricted antigen recognition,broad antitumor activity,and low risk of graft-versus-host disease(GVHD),have garnered significant interest in CAR-γδ T cell therapy.However,critical challenges including suboptimal in vitro expansion and low viral transduction efficiency severely hinder the research and clinical application of CAR-γδ T cells.This study aimed to establish an efficient platform for preparing CAR-γδ T cells by optimizing the in vitro expansion conditions of γδ T cells and refining lentiviral transduction strategies.Methods:We first optimized the expansion protocol for γδ T cells by screening various cytokine combinations and the concentrations of individual cytokines within combination,and evaluating cell purity,viability,fold expansion,and expressions of cytotoxicity and exhaustion markers to identify the optimal culture conditions.Subsequently,the transduction conditions for CAR-γδ T cells were improved by determining the optimal activation duration of γδ T cells prior to gene transfer,as well as the optimal multiplicity of infection(MOI)for lentiviral transduction.Finally,CAR-γδ T cells were successfully generated using the optimized protocol,and their cytotoxic activity against target cells was validated via calcein-release assay and flow cytometry,with a preliminary assessment of the potential risk of GVHD induction.Results:Experimental data demonstrated that,compared with the interleukin(IL)-2-only culture,the IL-2+IL-7+IL-15 combination significantly enhanced the expansion capacity of γδ T cells(876.50±238.35-fold vs 1 627.50±472.15-fold),cell purity(73.67%±1.53%vs 90.69%±2.00%),and cell viability(63.01%±7.05%vs 89.00%±3.61%).It also increased the expression of the cytotoxicity marker CD16(4.20%±1.73%vs 14.66%±0.58%)and reduced the expression of the exhaustion marker programmed death-1(PD-1)(35.67%±6.26%vs 21.10%±6.49%).A cytokine concentration gradient orthogonal assay further identified 10 ng/mL IL-7 and 10 ng/mL IL-15 as the optimal concentrations within the IL-2+IL-7+IL-15 combination.Gene transduction performed 96-120 h after activation using a multiplicity of infection(MOI)of 5-10 resulted in the highest transduction efficiency for CAR-γδ T cells(96 h:12.87%±4.35%;120 h:11.37%±2.35%).CAR-γδ T cells generated using the optimized system exhibited specific cytotoxic effects against tumor cells expressing the target antigen,and no evidence of GVHD induction was observed.Conclusion:CAR-γδ T cells produced using the IL-2+IL-7(10 ng/mL)+IL-15(10 ng/mL)regimen combined with a 96-120 h activation period prior to transduction using a multiplicity of infection(MOI)of 5-10 significantly outperformed conventional methods in terms of expansion efficiency,cell purity,and transduction efficiency.The synergistic antitumor effects mediated by both natural immune receptors and CAR-specific recognition,along with the initial absence of GVHD risk,provide critical technical support for the clinical translation of CAR-γδ T cell therapy,establishing a solid theoretical and practical foundation.

Background and purpose:Gallic acid(GA)induces tumor cells apoptosis and inhibits angiogenesis.Beyond directly attacking tumor cells,another crucial aspect of GA is its ability to modulate and enhance immune system function.For example,it can improve T cell metabolism,alleviate T cell exhaustion,and promote the formation of memory T cell phenotypes.Although several chimeric antigen receptor T(CAR-T)cells products have gained market approval,the technology still faces significant challenges.These limitations include off-target effects,a predisposition to T cell exhaustion and so on.Moreover,similar to exhaustion,cellular senescence is a major hindrance that impairs T cell function.This study aimed to investigate the effects of GA on the anti-tumor function of CAR-T cells both in vitro and in vivo.We further evaluated the impact of GA on CAR-T cells senescence and memory phenotypes,as well as the impact of GA and CAR-T cells on immune cell infiltration within the tumor microenvironment(TME).Methods:Second-generation CAR targeting mouse glypican 3(GPC3)and human epidermal growth factor receptor 2(HER2)were constructed to generate CAR-T cells.CAR-T cells were co-cultured with GA at a concentration of 5 μg/mL,and flow cytometry was used to assess the senescence status and memory phenotype of CAR-T cells and their killing ability against tumor cells at different effector-to-target ratios.Senescence markers included p53,p21,γ-H2AX and senescence-associated β-galactosidase(SA-β-gal),while CCR7 served as the memory phenotype marker.A subcutaneous tumor model was established to explore the effects of GA on the anti-tumor function of CAR-T cells and immune cell infiltration within the TME.Results:We successfully generated human HER2 and murine GPC3 CAR-T cells,achieving a purity of 30%-50%.GA enhanced the in vitro killing ability of CAR-T cells targeting mouse GPC3 and human HER2(P＜0.001)at different E:T ratios,delayed the senescence of mouse GPC3 CAR-T cells(p53,p21,γ-H2AX,P＜0.05;SA-β-gal,P＜0.001;CCR7,P＜0.001).And GA promoted the differentiation of CAR-T cells toward a memory phenotype(P＜0.001).Additionally,GPC3 CAR-T cells inhibited tumor cell growth(P＜0.05),prolonged mouse survival(P＜0.001),and enhanced the infiltration capacity of CAR-cells(P＜0.001)and endogenous immune cells[CD4+T cells,P＜0.05;CD8+T cells,P＜0.01;natural killer(NK)cells,P＜0.01].Conclusion:GA can enhance the cytotoxic activity of CAR-T cells in vitro,and delay the senescence of CAR-T cells.Furthermore,by modulating TME,GA improved immune cell infiltration,thereby augmenting the overall anti-tumor efficacy of CAR-T cells.

Background and purpose:Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases(LM)from solid tumors.A previous phase Ⅰ study demonstrated the safety and potential efficacy of intrathecal anti-programmed death receptor 1(anti-PD-1)for LM from melanoma.The synergistic efficacy of systemic chemotherapy combined with anti-PD-1 has been widely known.This study aimed to evaluate the safety and feasibility of intrathecal chemotherapy(pemetrexed)and anti-PD-1(toripalimab)for LM patients from solid tumors.Methods:The subjects were patients with LM from solid tumors who were treated at Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City.A 3+3 dose de-escalation strategy was implemented to determine the recommended dose with an initial dose of PD-1 inhibitor(toripalimab)40 mg and pemetrexed 15 mg.Pemetrexed was administered twice weekly for the initial 2 weeks of induction therapy,once weekly for the subsequent 4 weeks of consolidation therapy,and once monthly during maintenance therapy.PD-1 inhibitor was initiated at the 4th administration of pemetrexed,administered every 2 weeks for 6 weeks;subsequently,responders continued monthly maintenance therapy alongside pemetrexed.The primary objective was to assess safety based on adverse events and the recommended dose.All participants were observed to investigate the clinical response rate(CRR),disease control rate(DCR)and overall survival(OS).This study was approved by the ethics committee of Affiliated Huizhou Hospital of Guangzhou Medical University/Third People's Hospital of Huizhou City(ethics number:2024-KY-029-01).Results:Seven patients(male:3,female:4,median age:57 years)were enrolled between June and September 2024,including non-small cell lung cancer(6)and breast cancer(1).All patients presented with positive cerebrospinal fluid(CSF)cytology.Six patients presented LM-related neurological dysfunction.Five patients showed LM-related neuroimaging findings.Six patients completed the induction and consolidation therapy,and subsequently received maintenance therapy.One patient,due to bacterial meningitis,did not complete the final administration of toripalimab during consolidation therapy,and maintenance therapy was administered after infection control.Adverse events rate was 100%(7/7),including myelosuppression(100.00%,n=7),elevation of hepatic aminotransferases(42.86%,n=3),fatigue(28.57%,n=2)and hypothyroidism(14.29%,n=1).Three(42.86%)patients had grade 3 adverse events(myelosuppression).The immune-related adverse event(irAE)rate was 14.29%,manifested as hypothyroidism(Grade 2).No dose-limiting toxicity(DLT)was observed.Thus,no de-escalation was applied.The recommended dose was determined to be PD-1 inhibitor 40 mg in combination with pemetrexed 15 mg.Three patients showed improved neurological dysfunction,1 with CSF cytological response,and 2 with neuroimaging improvement.CRR was 57.14%(4/7)by response assessment in neuro-oncology(RANO)proposal criteria.DCR was 100%(7/7).Three patients exhibited abscopal effects with regression of brain metastasis lesions,primary lung lesion and mediastinal lymph nodes,respectively.As of April 10,2025,1 patient died.The median follow-up time was 7.7(5.9-9.3)months.The median OS was not reached with a 6-month OS rate of 85.71%.Conclusion:The combination therapy of intrathecal pemetrexed and a PD-1 inhibitor was well-tolerated and feasible,while also exhibiting potential clinical efficacy in treating LM from solid tumors including non-small cell lung cancer.

Background and purpose:Salivary duct carcinoma(SDC)is a group of rare and highly heterogeneous diseases.It predominantly arises in the parotid glands of middle-aged and elderly males,with high rates of recurrence and metastasis,as well as a poor prognosis.Currently,there is a lack of clinical data on SDC.This study aimed to evaluate the clinical characteristics of SDC patients and explore high-risk factors affecting prognosis,so as to provide clinical references for physicians.Methods:Clinical data of patients with primary SDC who were admitted to Tianjin Medical University Cancer Institute and Hospital and Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine from 2012 to 2024,were collected retrospectively.Inclusion criteria:① patients diagnosed with primary SDC;② availability of American Joint Committee on Cancer(AJCC)staging data.Exclusion criteria:① concurrent other malignant tumors;② incomplete or missing medical records;③ death due to non-SDC causes;④ duplicate cases from the two participating hospitals.Data retrieved encompassed epidemiological information(gender,age)and clinical details(time of diagnosis,tumor characteristics,treatment regimen,recurrence and metastasis status,and pathological data).Survival analysis was performed using the Kaplan-Meier method,and factors related to prognosis were explored through univariate COX proportional hazards regression model analysis.This study was approved by the Ethics Committee of Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine(ethics number:PH2023-B-016),and patient informed consent was waived.Results:A total of 87 patients with primary SDC were included in this study,among whom 77%were male,69%had primary lesions in the parotid gland,29.9%in the submandibular gland,and one patient had a primary lesion in the minor salivary gland of the nasal cavity.49.3%of the patients had concurrent cervical lymph node metastasis.The median overall survival(OS)of the entire group was 31.2 months,the median progression-free survival(PFS)was 20.3 months,and the 5-year OS rate was 52.6%.The 5-year OS rate for tumors originating from the parotid gland was 60%,which was better than the 32.9%for those originating from the submandibular gland.Among the 85 patients who received surgical treatment,65.9%underwent both resection of the primary tumor and neck dissection.Postoperative radiotherapy was administered to 49 patients.During the follow-up period,46%of the patients developed recurrence or metastasis,with lung and bone metastases being the most common.The median OS and local progression-free time in the postoperative radiotherapy group were significantly longer compared with those in the group without radiotherapy,however,the difference was not statistically significant.Conclusion:SDC is a malignant and aggressive disease that predominantly occurs in the parotid glands of middle-aged and elderly males,with a high rate of lymph node metastasis and poor prognosis.Clinically,it is recommended that patients with SDC undergo radical resection of the primary lesion and cervical lymph node dissection,combined with postoperative adjuvant radiotherapy.Targeted therapy and immunotherapy are worthy of further exploration.