Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tum...Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.展开更多
Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte a...Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.展开更多
Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs sele...Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.展开更多
BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concur...BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.展开更多
BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as le...BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of ch...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.展开更多
BACKGROUND Esophageal cancer is a serious global health concern with poor prognosis in advanced stages.Immune checkpoint inhibitors(ICIs)have shown promise in enhancing survival,but they are associated with immune-rel...BACKGROUND Esophageal cancer is a serious global health concern with poor prognosis in advanced stages.Immune checkpoint inhibitors(ICIs)have shown promise in enhancing survival,but they are associated with immune-related adverse events,including potentially life-threatening myocarditis.Moreover,ICI-induced myocarditis can be asymptomatic,necessitating early diagnosis.Specific risk factors and biomarkers for esophageal cancer remain poorly characterized.AIM To investigate the determinants of ICI-associated asymptomatic myocarditis in patients with esophageal cancer and explore potential early biomarkers.METHODS A retrospective analysis was conducted on 202 cancer patients who received treatment at Shanxi Province Cancer Hospital from July 2019 to July 2024.RESULTS Older age,male gender,and elevated creatine kinase isoenzymes(CK-MB)and CK levels were found to be significant risk factors for asymptomatic myocarditis.The myocarditis occurrence group had higher CK-MB(3.05 ng/mL vs 5.02 ng/mL;P<0.001)and CK levels(187.29 U/L vs 212.25 U/L;P=0.005),and the predictive value of age,gender,CK,and CK-MB was low[are under the receiver operating characteristic curve(AUC)=0.579-0.608].However,their combination in a predictive model showed improved diagnostic capability,with an AUC of 0.808.CONCLUSION Age,gender,and cardiac biomarker levels considerably contribute to the risk of ICI-related myocarditis in patients with esophageal cancer.The integration of these factors into a predictive model enhances early diagnosis,facilitating personalized risk management.展开更多
Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune ...Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune checkpoint inhibitors(ICIs)have emerged as critical therapeutic agents,targeting immune checkpoint pathways to restore antitumor immune responses.Combinations such as atezolizumab(anti-programmed cell death ligand 1 with bevacizumab antivascular endothelial growth factor),as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1(e.g.,ipilimumab and nivolumab),have demonstrated improved clinical outcome in selected patients.However,the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance.Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs.Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness.Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation,prebiotics,probiotics,and fecal microbiota transplantation to enhance ICIs responsiveness.This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC,with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.展开更多
This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single...This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single-cell RNA sequencing and immunohistochemistry,the study demonstrates significant CHEK1 overexpression in CRC tissues and identifies nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair pathways.These findings underscore the therapeutic potential of CHEK1 inhibition and highlight the need for further research to address gaps in CRC treatment.展开更多
Gastric cancer(GC)is one of the most common malignant tumors globally.The screening rate of GC is low,and the early symptoms are not obvious,which affects early diagnosis,and most patients have a poor prognosis.Variou...Gastric cancer(GC)is one of the most common malignant tumors globally.The screening rate of GC is low,and the early symptoms are not obvious,which affects early diagnosis,and most patients have a poor prognosis.Various treatments are available for GC,mainly surgery,chemotherapy,radiotherapy,targeted therapy and immunotherapy.Immunotherapy has made significant progress in recent years,especially for unresectable and metastatic GC.Immune checkpoints are proteins which can regulate the congenital and adaptive immu-nity,and are mainly expressed on immune cells.Immune checkpoints are crucial molecules that regulate the immune system,maintaining immune balance through positive or negative modulation.Tumors exploit negative immune checkpoint molecules to suppress immune responses,thereby evading immune surveillance.Immune checkpoint inhibitors(ICIs)can undo this inhibition,reactivating immune cells to destroy tumor cells.The prospects for the treatment of GC with ICIs are promising,but it also faces many difficulties and challenges.This minireview summarizes the progress of immune ICIs in GC,discusses current individualized strategies,and explores future development directions.展开更多
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of a...BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.展开更多
Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or e...Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).展开更多
Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary ...Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.展开更多
Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor i...Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.展开更多
BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings....BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.展开更多
BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascula...BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascular drugs used alone or in combination.The pathogenesis of AVB in this population may involve tumor-related factors,treatment-induced effects,or progression of underlying portal hypertension.Identifying high-risk factors for AVB is crucial for the management of this patient population.AIM To develop and validate a risk prediction model for AVB occurrence in cirrhotic HCC patients receiving ICI-based systemic therapy.METHODS This retrospective study analyzed 286 HCC patients(2021-2022)receiving ICIs(mono-/combination therapy),randomly split into training(n=184)and validation(n=102)cohorts.In the training cohort,bleeding vs nonbleeding groups were compared for general information,etiological data,laboratory indicators,tumor staging,systemic treatment drugs,variceal bleeding history,and endoscopic treatment history.Risk factors for AVB were identified and used to establish a logistic regression model for predicting bleeding,which was further validated in the validation cohort.RESULTS The bleeding group had significantly higher proportions of patients with platelet count≥100×10^(9)/L,alphafetoprotein≥400 ng/mL,tumor diameter≥5 cm,portal vein tumor thrombosis,ascites,bleeding history,prior endoscopic treatment,albumin-bilirubin grade level 2-3,fibrosis-4 index(FIB-4)≥4.57,and prognostic nutritional index<45 compared to the non-bleeding group.Multivariate analysis identified tumor diameter≥5 cm,portal vein thrombosis,bleeding history,and elevated FIB-4 as independent risk factors for bleeding(P<0.05).A predictive model based on these factors showed good discrimination,with area under the receiver operating characteristic curve values of 0.861(training)and 0.816(validation).CONCLUSION A history of pre-ICI bleeding significantly increases recurrent bleeding risk,necessitating close monitoring.The FIB-4 fibrosis model,combined with tumor features,can also serve as a predictive factor for bleeding.展开更多
Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages,with esophageal squamous cell carcinoma being the predominant subtype worldwide.Standard first-line chemotherapy provides limited surviv...Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages,with esophageal squamous cell carcinoma being the predominant subtype worldwide.Standard first-line chemotherapy provides limited survival benefits,with a median overall survival of less than 1 year.Recent advancements in immunotherapy,particularly immune checkpoint inhibitors(ICIs),have trans-formed the treatment landscape,improving overall survival and progression-free survival.However,response rates remain variable,with programmed death ligand 1(PD-L1)expression being the primary predictive biomarker.The variability in PD-L1 testing methods and immune microenvironment alterations after prior treatments complicate patient selection for ICIs.Several phase 3 trials,including KEYNOTE-590 and CheckMate 648,have demonstrated the efficacy of ICIs combined with chemotherapy,particularly in patients positive for PD-L1.Despite these advances,long-term survival remains low,emphasizing the need for better biomarkers and novel therapeutic strategies.This review explored current first-line treatment options for esophageal squamous cell carcinoma,challenges in biomarker-based patient selection,and emerging therapeutic approaches.展开更多
1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and co...1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and constitutes a major global health problem.^([1])The number of new cases in China accounted for 46.6%of the global liver cancer cases,and 47.1%of the global liver cancer deaths occurred in China.^([2])展开更多
Objectives:Checkpoint inhibitors have significantly improved outcomes in a number of malignancies.To determine the most effective course of treatment for head and neck squamous cell carcinoma(HNSCC),this systematic re...Objectives:Checkpoint inhibitors have significantly improved outcomes in a number of malignancies.To determine the most effective course of treatment for head and neck squamous cell carcinoma(HNSCC),this systematic review evaluated the efficacy of several therapeutic approaches based on immune checkpoint inhibitors(ICIs).Methods:A comprehensive evaluation of the literature was conducted,looking at randomized controlled trials(RCTs)that were published in Embase,PubMed,and the Cochrane Central Register of Controlled Trials since database establishment.The risk of bias of the enrolled studies was analyzed using The Review Manager(RevMan)5.4.Using network meta-analyses(NMA),the relative treatment effects on overall survival(OS)and progression-free survival(PFS)from qualifying randomized controlled trials were synthesized and evaluated.Results:Regarding OS,compared with nivolumab plus chemotherapy,chemotherapy(Hazard ratio(HR)2.1,95%Confidence interval=(CI):1.2,3.4)showed a treatment disadvantage.Meanwhile,nivolumab plus chemotherapy may represent the most efficient(57.89%)and has a lower cost among all the treatments enrolled in this study for advanced HNSCC.Regarding PFS,compared with nivolumab plus ipilimumab,nivolumab plus chemotherapy(HR 0.4,95%CI:0.2,0.8)showed=treatment superiority.Additionally,nivolumab plus chemotherapy(77.18%)has the longest PFS among all interventions.Conclusion:Taking into account OS and PFS,the combination of nivolumab plus chemotherapy may appear to be the most effective option and is associated with a comparatively lower cost among all treatments included in this network meta-analysis,thereby recommending its use as a first-line therapy for HNSCC.Registration:INPLASY(2024070073).展开更多
基金Supported by 2021 Key Topic of Qinghai Provincial Health System–Guiding Plan Topic,No.2021-WJZDX-43.
文摘Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.
基金Supported by the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.
文摘Treatment with immune checkpoint inhibitors(ICIs)is an innovative therapy for managing certain types of malignancy and has the potential to improve overall patient survival significantly.The most widely used ICIs selectively target different receptors comprising programmed cell death-1 receptor,programmed cell death-ligand 1 receptor,and cytotoxic T lymphocyte antigen 4 receptor.The widespread utilization of ICIs over the past several years,however,is frequently accompanied by immune-related adverse events(irAEs)that substantially impact the patient’s quality of life,particularly those affecting the digestive system,including both the upper and lower gastrointestinal tract.Based on a literature search covering databases such as PubMed,Web of Science,Embase,and the Cochrane Library,we present an insight into primary gastrointestinal irAEs,with a special focus on endoscopic manifestations.Additionally,we analyze data regarding the pathogenetic mechanisms,diagnostic approaches,histological characteristics,and proposed therapeutic interventions for managing irAEs involving the gastrointestinal tract.
文摘BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.
基金Supported by the Capital’s Funds for Health Improvement and Research,No.SF202222175.
文摘BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.
基金Supported by Innovation Project of Guangxi Graduate Education,No.YCBZ2023096Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442+1 种基金China Undergraduate Innovation and Entrepreneurship Training Program,No.S202410598185Future Academic Star of Guangxi Medical University,No.WLXSZX24101.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant tumor characterized by a high mortality rate,with significant challenges persisting in the identification and management of its metastatic stage.The role of checkpoint kinase 1(CHEK1),a cell cycle checkpoint kinase,in CRC has not been fully clarified.We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells,indicating its potential as a novel therapeutic target for CRC therapy.AIM To investigate the expression and function of CHEK1 in CRC,this study utilizes single-cell RNA sequencing and tissue microarray data.METHODS Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset,and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues.We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expre-ssion in CRC.Molecular docking experiments were performed to explore the in-teraction between CHEK1 and the potential drug nitidine chloride(NC),as well as to investigate the influence of CHEK1 on CRC cell proliferation.RESULTS We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC,with marked upregulation of its mRNA levels in CRC tissues.Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues,and the receiver operating characteristic curve demonstrated high accuracy(area under the curve=0.964)for CHEK1 as a biomarker.Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC(standard mean difference=1.81,P<0.01),with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88,respectively.Molecular docking studies indicated that NC specifically targeted CHEK1,while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.CONCLUSION Upregulation of CHEK1 promotes CRC cell proliferation.However,the dataset's diversity is limited,requiring further investigation into its specific mechanisms.
文摘BACKGROUND Esophageal cancer is a serious global health concern with poor prognosis in advanced stages.Immune checkpoint inhibitors(ICIs)have shown promise in enhancing survival,but they are associated with immune-related adverse events,including potentially life-threatening myocarditis.Moreover,ICI-induced myocarditis can be asymptomatic,necessitating early diagnosis.Specific risk factors and biomarkers for esophageal cancer remain poorly characterized.AIM To investigate the determinants of ICI-associated asymptomatic myocarditis in patients with esophageal cancer and explore potential early biomarkers.METHODS A retrospective analysis was conducted on 202 cancer patients who received treatment at Shanxi Province Cancer Hospital from July 2019 to July 2024.RESULTS Older age,male gender,and elevated creatine kinase isoenzymes(CK-MB)and CK levels were found to be significant risk factors for asymptomatic myocarditis.The myocarditis occurrence group had higher CK-MB(3.05 ng/mL vs 5.02 ng/mL;P<0.001)and CK levels(187.29 U/L vs 212.25 U/L;P=0.005),and the predictive value of age,gender,CK,and CK-MB was low[are under the receiver operating characteristic curve(AUC)=0.579-0.608].However,their combination in a predictive model showed improved diagnostic capability,with an AUC of 0.808.CONCLUSION Age,gender,and cardiac biomarker levels considerably contribute to the risk of ICI-related myocarditis in patients with esophageal cancer.The integration of these factors into a predictive model enhances early diagnosis,facilitating personalized risk management.
文摘Hepatocellular carcinoma(HCC),a primary malignancy of the liver and leading cause of cancer-related mortality worldwide,poses substantial therapeutic challenges,particularly in advanced and unresectable stages.Immune checkpoint inhibitors(ICIs)have emerged as critical therapeutic agents,targeting immune checkpoint pathways to restore antitumor immune responses.Combinations such as atezolizumab(anti-programmed cell death ligand 1 with bevacizumab antivascular endothelial growth factor),as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1(e.g.,ipilimumab and nivolumab),have demonstrated improved clinical outcome in selected patients.However,the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance.Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs.Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness.Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation,prebiotics,probiotics,and fecal microbiota transplantation to enhance ICIs responsiveness.This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC,with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.
文摘This editorial provides insights into the pivotal role of checkpoint kinase 1(CHEK1)as both a biomarker and therapeutic target in colorectal cancer(CRC),based on findings from a recent study by Pang et al.Using single-cell RNA sequencing and immunohistochemistry,the study demonstrates significant CHEK1 overexpression in CRC tissues and identifies nitidine chloride as a potent CHEK1 inhibitor that disrupts DNA damage repair pathways.These findings underscore the therapeutic potential of CHEK1 inhibition and highlight the need for further research to address gaps in CRC treatment.
文摘Gastric cancer(GC)is one of the most common malignant tumors globally.The screening rate of GC is low,and the early symptoms are not obvious,which affects early diagnosis,and most patients have a poor prognosis.Various treatments are available for GC,mainly surgery,chemotherapy,radiotherapy,targeted therapy and immunotherapy.Immunotherapy has made significant progress in recent years,especially for unresectable and metastatic GC.Immune checkpoints are proteins which can regulate the congenital and adaptive immu-nity,and are mainly expressed on immune cells.Immune checkpoints are crucial molecules that regulate the immune system,maintaining immune balance through positive or negative modulation.Tumors exploit negative immune checkpoint molecules to suppress immune responses,thereby evading immune surveillance.Immune checkpoint inhibitors(ICIs)can undo this inhibition,reactivating immune cells to destroy tumor cells.The prospects for the treatment of GC with ICIs are promising,but it also faces many difficulties and challenges.This minireview summarizes the progress of immune ICIs in GC,discusses current individualized strategies,and explores future development directions.
基金Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
基金Supported by the Key Research and Development Projects of Anhui Province,No.202104j07020048National Key Research and Development Program of China,No.2022YFA1304500.
文摘BACKGROUND Currently,there is a lack of effective adjuvant therapies for patients at high-risk of recurrent hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC)after radical resection.Given the efficacy of anti-programmed death 1/anti-programmed death ligand 1 plus anti-vascular endothelial growth factor receptor agents in advanced HCC,we conducted this study to investigate the efficacy of this combination regimen in the postoperative adjuvant treatment of patients with HBV-HCC.AIM To evaluate the value of postoperative combined therapy(PCT)with anti-programmed death 1/anti-programmed death ligand 1 and anti-vascular endothelial growth factor receptor agents in patients with HBV-HCC.METHODS Patients with HBV-HCC who underwent radical resection surgery at Anhui Provincial Hospital Affiliated to Anhui Medical University between July 2020 and April 2023 were included.Recurrence-free survival(RFS)and overall survival were assessed using propensity score matching and inverse probability of treatment weighting.Cox regression analysis was used to identify factors affecting recurrence,and subgroup analysis was conducted to investigate the impact of medications on different populations.Treatment-related adverse events and liver function measurements were evaluated.RESULTS A total of 150 patients were recruited,of whom 30 underwent PCT and 120 did not.After adjusting for confounders,patients who underwent PCT had better RFS at 6 and 12 months than those who did not(P>0.05).Similar results were observed in the Kaplan-Meier curves after propensity score matching or inverse probability of treatment weighting,although the difference was not statistically significant(P>0.05).A maximum diameter of>5 cm,vascular invasion,satellite nodules,and high gamma-glutamyl transferase levels were independent risk factors for recurrence(P<0.05).No significant interaction effects were observed in subgroup analyses.The most prevalent adverse event was hypertension(66.7%).PCT was associated with an increased risk of hepatic impairment which may predict RFS rates(P=0.041).CONCLUSION The recurrence rate was not significantly reduced in patients who underwent PCT.Hepatic impairment during treatment may indicate recurrence,and close monitoring of liver function and HBV infection is recommended.
基金supported by grants from the National Natural Science Foundation of China(Nos.82373372 and U22A20330)Key Project of Research and Development Plan in Heilongjiang Province(Nos.2022ZX06C01 and JD2023SJ40)+1 种基金National Cancer Center Climbing Fund(No.NCC201908A03)Beijing Xisike Clinical Oncology Research Foundation(No.Y-HR2020MS-0900).
文摘Psoriasiform rash is a notable immune-related cutaneous adverse event(ircAE)accounting for approximately 5%of all ircAEs1,2.Patients with cancer and pre-existing psoriasis face elevated risk of disease recurrence or exacerbation after receiving immune checkpoint inhibitors(ICIs).A European multicenter study has reported a reactivation rate of 28.7%in this population3.ICIs also trigger de novo psoriatic lesions,which mirror conventional lesion subtypes(plaque,guttate,erythrodermic,or pustular).
文摘Esophageal squamous cell carcinoma(ESCC)remains a daunting global health concern.It is marked by aggressive progression and poor survival.While immunotherapy has emerged as a promising treatment modality,both primary and acquired resistance continue to limit its clinical impact,leaving many patients without durable benefits(e.g.,CheckMate-648,ESCORT-1st).This review explains resistance mechanisms and suggests new strategies to improve outcomes.These mechanisms include immunosuppressive cells(Treg cells,myeloid-derived suppressor cells),inhibitory cytokines,molecular alterations involving programmed death 1/programmed death-ligand 1 signaling,and impaired antigen presentation.We also highlight key clinical trials—for example,CheckMate-648 and ESCORT-1st—that reveal both the potential and pitfalls of current immune checkpoint blockade strategies,underscoring the need for robust predictive biomarkers.Moreover,we examine cutting-edge tactics to overcome resistance,including combination regimens,tumor microenvironment remodeling,and tailored treatment approaches rooted in the patient’s unique genomic and immunologic landscape.
基金supported by the National Key Research and Development Program of China(No.2022YFE0102100)the National Natural Science Foundation of China(Nos.U22A20307 and 81930041)。
文摘Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade(ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified;some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration(FDA) for clinical treatment. However, limited responses and immune-related adverse events(ir AEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
基金Supported by Hebei Provincial Medical Science Research Project Program,No.20240164.
文摘BACKGROUND Colorectal cancer(CRC)is among the most prevalent and deadly cancers globally,particularly in China.Treatment challenges remain in advanced and metastatic cases,especially in third-and fourth-line settings.The combination of targeted therapies with immune checkpoint inhibitors(ICIs)has shown potential in addressing the limitations of single-agent treatments.AIM To evaluate the efficacy and safety of targeted therapy(TT)alone and in combination with ICIs for metastatic CRC(mCRC).METHODS A multicenter retrospective observational study was conducted to evaluate the efficacy and safety of TT alone and in combination with ICIs for mCRC.A total of 99 patients treated with regorafenib or fruquintinib,with or without ICIs,were enrolled.Propensity score matching(PSM)and inverse probability weighting(IPW)were employed to balance baseline characteristics.The primary endpoint was progression-free survival(PFS),while overall survival(OS)and safety were secondary.RESULTS Patients who received combined therapy showed significantly longer median PFS rates compared to those who underwent TT in all analyses(original:6.0 vs 3.4 months,P<0.01;PSM:6.15 vs 4.25 months,P<0.05;IPW:5.6 vs 3.3 months,P<0.01).Although the median OS showed a trend toward improvement in the combination group,the difference was insignificant.Cox regression analysis revealed that combining TT with ICIs significantly reduced the risk of disease progression(hazard ratio=0.38,P<0.001).Adverse events(AEs)were generally manageable with both regimens,while serious AEs(grade 3-4)were primarily hypertension,fatigue,and reduced platelet counts.All AEs were controlled effectively by symptomatic treatment or discontinuation of the drug,and no treatment-related deaths were observed.CONCLUSION The combination of TT with ICIs offers a significant advantage in terms of PFS for patients with advanced mCRC,accompanied by a favorable safety profile.These findings underscore the benefits of combination therapy in this setting,warranting further investigation in larger prospective clinical trials.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034AHebei Province 2025 Traditional Chinese Medicine Scientific Research Project Plan,No.T2025008.
文摘BACKGROUND Acute variceal bleeding(AVB)represents a life-threatening complication in hepatocellular carcinoma(HCC)patients undergoing systemic therapy,mainly including immune checkpoint inhibitors(ICIs)and antivascular drugs used alone or in combination.The pathogenesis of AVB in this population may involve tumor-related factors,treatment-induced effects,or progression of underlying portal hypertension.Identifying high-risk factors for AVB is crucial for the management of this patient population.AIM To develop and validate a risk prediction model for AVB occurrence in cirrhotic HCC patients receiving ICI-based systemic therapy.METHODS This retrospective study analyzed 286 HCC patients(2021-2022)receiving ICIs(mono-/combination therapy),randomly split into training(n=184)and validation(n=102)cohorts.In the training cohort,bleeding vs nonbleeding groups were compared for general information,etiological data,laboratory indicators,tumor staging,systemic treatment drugs,variceal bleeding history,and endoscopic treatment history.Risk factors for AVB were identified and used to establish a logistic regression model for predicting bleeding,which was further validated in the validation cohort.RESULTS The bleeding group had significantly higher proportions of patients with platelet count≥100×10^(9)/L,alphafetoprotein≥400 ng/mL,tumor diameter≥5 cm,portal vein tumor thrombosis,ascites,bleeding history,prior endoscopic treatment,albumin-bilirubin grade level 2-3,fibrosis-4 index(FIB-4)≥4.57,and prognostic nutritional index<45 compared to the non-bleeding group.Multivariate analysis identified tumor diameter≥5 cm,portal vein thrombosis,bleeding history,and elevated FIB-4 as independent risk factors for bleeding(P<0.05).A predictive model based on these factors showed good discrimination,with area under the receiver operating characteristic curve values of 0.861(training)and 0.816(validation).CONCLUSION A history of pre-ICI bleeding significantly increases recurrent bleeding risk,necessitating close monitoring.The FIB-4 fibrosis model,combined with tumor features,can also serve as a predictive factor for bleeding.
文摘Esophageal cancer is an aggressive malignancy often diagnosed at advanced stages,with esophageal squamous cell carcinoma being the predominant subtype worldwide.Standard first-line chemotherapy provides limited survival benefits,with a median overall survival of less than 1 year.Recent advancements in immunotherapy,particularly immune checkpoint inhibitors(ICIs),have trans-formed the treatment landscape,improving overall survival and progression-free survival.However,response rates remain variable,with programmed death ligand 1(PD-L1)expression being the primary predictive biomarker.The variability in PD-L1 testing methods and immune microenvironment alterations after prior treatments complicate patient selection for ICIs.Several phase 3 trials,including KEYNOTE-590 and CheckMate 648,have demonstrated the efficacy of ICIs combined with chemotherapy,particularly in patients positive for PD-L1.Despite these advances,long-term survival remains low,emphasizing the need for better biomarkers and novel therapeutic strategies.This review explored current first-line treatment options for esophageal squamous cell carcinoma,challenges in biomarker-based patient selection,and emerging therapeutic approaches.
基金Supported by a grant from the Talent Exchange Service Center of National Health Commission(RCLX2315049)。
文摘1.Introduction Liver cancer is the sixth leading cause of cancer and the third leading cause of cancer-related deaths globally(GLOBOCAN).Hepatocellular carcinoma(HCC)represents about 90%of primary liver cancers and constitutes a major global health problem.^([1])The number of new cases in China accounted for 46.6%of the global liver cancer cases,and 47.1%of the global liver cancer deaths occurred in China.^([2])
文摘Objectives:Checkpoint inhibitors have significantly improved outcomes in a number of malignancies.To determine the most effective course of treatment for head and neck squamous cell carcinoma(HNSCC),this systematic review evaluated the efficacy of several therapeutic approaches based on immune checkpoint inhibitors(ICIs).Methods:A comprehensive evaluation of the literature was conducted,looking at randomized controlled trials(RCTs)that were published in Embase,PubMed,and the Cochrane Central Register of Controlled Trials since database establishment.The risk of bias of the enrolled studies was analyzed using The Review Manager(RevMan)5.4.Using network meta-analyses(NMA),the relative treatment effects on overall survival(OS)and progression-free survival(PFS)from qualifying randomized controlled trials were synthesized and evaluated.Results:Regarding OS,compared with nivolumab plus chemotherapy,chemotherapy(Hazard ratio(HR)2.1,95%Confidence interval=(CI):1.2,3.4)showed a treatment disadvantage.Meanwhile,nivolumab plus chemotherapy may represent the most efficient(57.89%)and has a lower cost among all the treatments enrolled in this study for advanced HNSCC.Regarding PFS,compared with nivolumab plus ipilimumab,nivolumab plus chemotherapy(HR 0.4,95%CI:0.2,0.8)showed=treatment superiority.Additionally,nivolumab plus chemotherapy(77.18%)has the longest PFS among all interventions.Conclusion:Taking into account OS and PFS,the combination of nivolumab plus chemotherapy may appear to be the most effective option and is associated with a comparatively lower cost among all treatments included in this network meta-analysis,thereby recommending its use as a first-line therapy for HNSCC.Registration:INPLASY(2024070073).
