Objective:Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer(NSCLC).However,its clinical application remains limited by the lack of reliable and non-in...Objective:Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer(NSCLC).However,its clinical application remains limited by the lack of reliable and non-invasive biomarkers.Although existing histological biomarkers such as programmed death-ligand 1(PD-L1)and tumor mutation burden(TMB)can be used for reference,they rely on invasive sampling and are susceptible to tumor heterogeneity.This study evaluated a series of peripheral blood inflammation-related indicators,including neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and interleukin-6(IL-6),to explore their potential as non-invasive predictive and prognostic biomarkers for NSCLC.Furthermore,a prediction model based on the above indicators was constructed to provide a practical and feasible tool for optimizing individualized clinical management in patients with resectable NSCLC.Methods:A retrospective analysis was conducted on 144 patients with resectable(stageⅠB-ⅢB)NSCLC who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at the Second Xiangya Hospital,Central South University,between 2019 and 2022.Peripheral blood-related indicators at baseline and before surgery were collected.Clinical data that might influence treatment efficacy were also recorded,including age,sex,body mass index,smoking history,pathological type,clinical stage,and use of immune checkpoint inhibitors.The relationships between peripheral blood inflammatory indicators(NLR,LMR,PLR,SII,and IL-6)and objective response rate(ORR),pathological complete response(pCR),major pathological response(MPR),and disease-free survival(DFS)were analyzed.Receiver operating characteristic(ROC)curves were used to determine optimal cutoff values for each indicator.A prediction model for the efficacy of neoadjuvant immunotherapy in NSCLC was constructed using least absolute shrinkage and selection operator(LASSO)regression combined with a multivariate Cox proportional hazards model.Results:The median age of included patients was 58 years,and 91.0%(131/144)were male.Among pathological types,squamous cell carcinoma accounted for 74.3%(107/144),adenocarcinoma for 22.9%(33/144),and other types for 4 cases.The overall ORR,pCR,and MPR rates were 69.2%,42.4%,and 61.5%,respectively.Univariate analysis showed that patients with squamous cell carcinoma had significantly higher ORR(P=0.007),pCR(P=0.027),and MPR(P=0.019).Lower baseline LMR was associated with a higher ORR.Elevated baseline PLR was significantly associated with pCR(P=0.014)and MPR(P=0.043).Increased baseline SII(P=0.015)and IL-6(P=0.043)were associated with higher MPR rates.Multivariate analysis showed that squamous cell carcinoma was an independent predictor of MPR(OR=7.34,95%CI 1.02 to 52.51,P=0.047),and lower baseline LMR was an independent predictor of ORR in NSCLC(OR=0.21,95%CI 0.05 to 0.92,cutoff value 3.12;P=0.04).Further survival analysis indicated that low baseline NLR(HR=0.363,P=0.014),low preoperative LMR(HR=0.260,P=0.018),and high preoperative SII(HR=0.278,P=0.003)significantly reduced the risk of DFS.A prediction model including 9 factors(age,pathological type,baseline NLR,baseline neutrophils,baseline IL-6,baseline monocytes,preoperative lymphocytes,preoperative SII,and preoperative LMR)was established for predicting the efficacy of neoadjuvant immunotherapy in NSCLC,with an AUC of 0.818.Conclusion:Neoadjuvant immunotherapy demonstrates favorable clinical efficacy in patients with NSCLC,particularly in those with squamous cell carcinoma.Meanwhile,peripheral blood inflammation-related indicators may serve as important biomarkers for predicting the efficacy and prognosis of neoadjuvant immunotherapy in NSCLC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide.Despite improvements in surgical techniques and systemic therapies,long-term outcomes after liver resection are lim...BACKGROUND Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide.Despite improvements in surgical techniques and systemic therapies,long-term outcomes after liver resection are limited by high recurrence rates.While adjuvant strategies have shown limited benefit,the role of neoadjuvant immunotherapy in resectable HCC is still under investigation.AIM To assess the efficacy,feasibility,and safety of neoadjuvant immunotherapy in resectable HCC through a meta-analysis of current literature.METHODS A systematic search was conducted across PubMed,Web of Science,EMBASE,Cochrane Library,and Scopus for studies published in the past five years evaluating neoadjuvant immunotherapy in resectable HCC.Primary endpoints included major pathological response(MPR),pathological complete response(pCR),overall response rate(ORR),resection rate,and grade 3-4 treatment-related adverse events(TRAEs).A random-effects meta-analysis was conducted using log odds ratios(ORs)and pooled event rates were calculated to provide absolute estimates of clinical endpoints.RESULTS Twelve studies were included in the final analysis.The pooled ORs were 0.28(95%CI:0.19-0.41)for MPR,0.54(95%CI:0.25-1.14)for ORR,0.26(95%CI:0.11-0.66)for pCR,5.37(95%CI:2.70-10.66)for resection rate,and 0.33(95%CI:0.22-0.50)for grade 3-4 TRAEs.Corresponding pooled event rates were 19%for MPR,35%for ORR,22%for pCR,81%for resection feasibility,and 19%for severe TRAEs.CONCLUSION Neoadjuvant immunotherapy appears to be a feasible and safe approach in patients with resectable HCC,achieving moderate pathological responses and high resection rates.展开更多
Background:Lung cancer is a major public health concern,and postoperative rehabilitation is crucial for patients.With the emergence of neoadjuvant immunotherapy,understanding the home-based rehabilitation needs of pos...Background:Lung cancer is a major public health concern,and postoperative rehabilitation is crucial for patients.With the emergence of neoadjuvant immunotherapy,understanding the home-based rehabilitation needs of postoperative lung cancer patients who have undergone this therapy has become important.Methods:This qualitative study employed grounded theory.Data were collected through face-to-face,in-depth,semi-structured interviews from February to June 2023 with 15 postoperative lung cancer patients who received routine neoadjuvant immunotherapy.Results:Five key themes emerged:(1)Limited exposure to home-based rehabilitation;(2)Unmet demand for home-based rehabilitation;(3)Factors hindering home-based rehabilitation;(4)Specific home-based rehabilitation needs;(5)Recommendations and observations.The findings revealed that patients lack awareness of home-based rehabilitation,have unmet rehabilitation needs,and require timely implementation of such programs to enhance rehabilitation management and quality of life.Conclusion:This study emphasizes the importance of developing and implementing home-based rehabilitation programs for lung cancer patients who have undergone neoadjuvant immunotherapy.These programs should address the identified needs and recommendations to improve rehabilitation outcomes and quality of life.Future efforts should focus on large-scale implementation and evaluation of these programs.展开更多
Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell car...Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell carcinoma.Patients with squamous cell carcinoma of the temporal bone are often at advanced stages when diagnosed,and lose the chance for surgery.Neoadjuvant immunotherapy has recently been approved as the first-line treatment for refractory recurrent/metastatic squamous cell carcinoma of the head and neck.However,it remains to be determined whether neoadjuvant immunotherapy can be used as the first-line treatment for temporal bone squamous cell carcinoma to reduce the tumor stage before surgery,or as a palliative treatment for patients with unresectable advanced stage carcinoma.The present study reviews the development of immunotherapy and its clinical application in head and neck squamous cell carcinoma,summarizes the treatment of temporal bone squamous cell carcinoma,and prospects the neoadjuvant immunotherapy as the first-line treatment for temporal bone squamous cell carcinoma.展开更多
Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ...Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ,and despite perioperative therapy plus D2 gastrectomy being the standard of care,long-term survival remains poor[3,4].展开更多
BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy co...BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.展开更多
BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain lim...BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.展开更多
Background:The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy(MIG)for locally advanced gastric cancer(LAGC)remains controversial.This study aimed to compare short-term outcomes between MIG after...Background:The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy(MIG)for locally advanced gastric cancer(LAGC)remains controversial.This study aimed to compare short-term outcomes between MIG after neoadjuvant chemo-immunotherapy(NICT-MIG)and MIG after neoadjuvant chemotherapy alone(NCT-MIG),and determine risk factors for post-operative complications(POCs).Methods:This retrospective study included clinicopathologic data from 193 patients who underwent NCT-MIG or NICT-MIG between January 2020 and February 2023 in the Department of General Surgery,Chinese People’s Liberation Army General Hospital First Medical Center(Beijing,China).Propensity score-matched analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables and short-term outcomes were compared between the two groups.Results:The baseline characteristics were comparable between 49 patients in the NICT-MIG group and 86 patients in the NCT-MIG group after propensity score matching.Objective and pathologic complete response rates were significantly higher in the NICT-MIG group than in the NCT-MIG group(P<0.05).The overall incidence of treat-related adverse events,intraoperative bleeding,operation time,number of retrieved lymph nodes,time to the first flatus,post-operative duration of hospitalization,overall morbidity,and severe morbidity were comparable between the NCT-MIG and NICT-MIG groups(P>0.05).By multivariate logistic analysis,estimated blood loss of>200mL(P=0.010)and prognostic nutritional index(PNI)score of<45(P=0.003)were independent risk factors for POCs after MIG following neoadjuvant therapy.Conclusions:Safety and feasibility of NICT were comparable to those of NCT in patients undergoing MIG for LAGC.Patients with an estimated blood loss of>200mL or a PNI score of<45 should be carefully evaluated for increased POCs risk.展开更多
Immune checkpoint inhibitors(ICIs)have transformed the treatment landscape for resectable non-small cell lung cancer.Numerous trials have explored the use of ICIs,either as monotherapy or in combination with other the...Immune checkpoint inhibitors(ICIs)have transformed the treatment landscape for resectable non-small cell lung cancer.Numerous trials have explored the use of ICIs,either as monotherapy or in combination with other therapies,in the neoadjuvant setting for stage Ⅰ-Ⅲ non-small cell lung cancer.Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy,with a high pathological response rate and significantly improved event-free survival.This review summarizes the findings of Phase Ⅰ-Ⅲ clinical trials investigating various neoadjuvant regimens,including ICI monotherapy,ICI therapy combined with chemother-apy,ICI plus anti-angiogenic therapy,dual ICI therapy,and ICI therapy in combination with radiotherapy or chemoradiotherapy.We discuss the benefits and outcomes associated with each approach.Despite the results being promising,several unresolved issues remain,including identification of reliable biomarkers,the appropri-ate duration of therapy,the optimal treatment regimen for tumors with high programmed cell death ligand 1(PD-L1)expression,the false-negative pathological complete response rate,and the role of digital pathology in assessing the response to treatment.Resistance to immunotherapy,in particular,remains a significant barrier to effective use of ICIs.Given the critical influence of the tumor microenvironment(TME)on the response to treat-ment,we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy.We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity,therapy-driven TME remodeling,and overcoming resistance to therapy.Finally,we propose future directions for advancements in personalized neoadjuvant immunotherapy.展开更多
Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global hea...Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.展开更多
Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in ...Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.展开更多
The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND tr...The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and epirubicin/cyclophosphamide-based chemotherapy as a neoadjuvant treatment for TNBC(ChiCTR2000035262).The primary endpoint was pathological complete response(pCR),with the secondary endpoints including safety assessment and objective response rate(ORR).ScRNA-seq,bulk RNA-seq,TCR-seq,cyTOF and WES were performed on pre-treatment and post-treatment samples.Among 53 total enrolled patients,44 completed the combined neoadjuvant therapy,and 30 of 44 patients(68.18%)achieved pCR.Additionally,14 out of 44 patients had a complete response(31.82%),with an ORR of 93.18%.The most commonly observed treatment-related adverse events(TRAEs)were alopecia,nausea and liver injury with 6 cases classified as grade 3 or higher adverse events.Immune response-related pathways,including TNF signaling pathway,T cell receptor signaling pathway,were enriched in pCR group.Pre-treatment model was identified and construct to predict response to immunotherapy.CDKN1A+CD8 T lymphocytes were enriched in pCR group after neoadjuvant immunotherapy.Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment effcacy.In conclusion,neoadjuvant treatment of tislelizumab with nab-paclitaxel and anthracycline-based chemotherapy showed promising clinical activity and was well-tolerated among TNBC patients,without high incidence of TRAEs.These findings provide evidence supporting neoadjuvant tislelizumab with chemotherapy as an effective rational approach for treating TNBC.展开更多
Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,p...Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,patients’clinical outcomes with different regimens are uncertain.Our study aims to examine the efficacy of neoadjuvant immunotherapy(NAIT)for NSCLC patients and compare the overall survival(OS)and event-free survival(EFS)of patients receiving different NAT regimens.Methods:This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1,2016 and July 31,2022.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.Results:With a median follow-up of 27.5 months,the 1-year OS rates were 98.8%and 96.2%,and the 2-year OS rates were 96.6%and 85.8%in patients of the NAIT and neoadjuvant chemotherapy(NACT)group,respectively(hazard ratio[HR],0.339;95%confidence interval[CI],0.160-0.720;P=0.003).The 1-year EFS rates were 96.0%and 88.0%,and the 2-year EFS rates were 92.0%and 77.7%for patients in the NAIT and NACT groups,respectively(HR,0.438;95%CI,0.276-0.846;P=0.010).For patients who did not achieve pathological complete response(pCR),significantly longer OS(P=0.012)and EFS(P=0.019)were observed in patients receiving NAIT than those receiving NACT.Different NAT regimens had little effect on surgery and the postoperative length of stay(6[4,7]days vs.6[4,7]days,Z=-0.227,P=0.820).Conclusions:NAIT exhibited superior efficacy to NACT for NSCLC,resulting in longer OS and EFS.The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.展开更多
Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key cl...Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.展开更多
基金supported by the Key Scientific Research Project of the Hunan Provincial Department of Science and Technology(2024PT5102)the Outstanding Youth Program under the Scientific Research Project of the Hunan Provincial Department of Education(23B0011)+1 种基金the Wu Jieping Medical Foundation(320.6750.2023-05-39)the Postgraduate Innovative Project of Central South University(2024XQLH151),China.
文摘Objective:Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer(NSCLC).However,its clinical application remains limited by the lack of reliable and non-invasive biomarkers.Although existing histological biomarkers such as programmed death-ligand 1(PD-L1)and tumor mutation burden(TMB)can be used for reference,they rely on invasive sampling and are susceptible to tumor heterogeneity.This study evaluated a series of peripheral blood inflammation-related indicators,including neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and interleukin-6(IL-6),to explore their potential as non-invasive predictive and prognostic biomarkers for NSCLC.Furthermore,a prediction model based on the above indicators was constructed to provide a practical and feasible tool for optimizing individualized clinical management in patients with resectable NSCLC.Methods:A retrospective analysis was conducted on 144 patients with resectable(stageⅠB-ⅢB)NSCLC who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at the Second Xiangya Hospital,Central South University,between 2019 and 2022.Peripheral blood-related indicators at baseline and before surgery were collected.Clinical data that might influence treatment efficacy were also recorded,including age,sex,body mass index,smoking history,pathological type,clinical stage,and use of immune checkpoint inhibitors.The relationships between peripheral blood inflammatory indicators(NLR,LMR,PLR,SII,and IL-6)and objective response rate(ORR),pathological complete response(pCR),major pathological response(MPR),and disease-free survival(DFS)were analyzed.Receiver operating characteristic(ROC)curves were used to determine optimal cutoff values for each indicator.A prediction model for the efficacy of neoadjuvant immunotherapy in NSCLC was constructed using least absolute shrinkage and selection operator(LASSO)regression combined with a multivariate Cox proportional hazards model.Results:The median age of included patients was 58 years,and 91.0%(131/144)were male.Among pathological types,squamous cell carcinoma accounted for 74.3%(107/144),adenocarcinoma for 22.9%(33/144),and other types for 4 cases.The overall ORR,pCR,and MPR rates were 69.2%,42.4%,and 61.5%,respectively.Univariate analysis showed that patients with squamous cell carcinoma had significantly higher ORR(P=0.007),pCR(P=0.027),and MPR(P=0.019).Lower baseline LMR was associated with a higher ORR.Elevated baseline PLR was significantly associated with pCR(P=0.014)and MPR(P=0.043).Increased baseline SII(P=0.015)and IL-6(P=0.043)were associated with higher MPR rates.Multivariate analysis showed that squamous cell carcinoma was an independent predictor of MPR(OR=7.34,95%CI 1.02 to 52.51,P=0.047),and lower baseline LMR was an independent predictor of ORR in NSCLC(OR=0.21,95%CI 0.05 to 0.92,cutoff value 3.12;P=0.04).Further survival analysis indicated that low baseline NLR(HR=0.363,P=0.014),low preoperative LMR(HR=0.260,P=0.018),and high preoperative SII(HR=0.278,P=0.003)significantly reduced the risk of DFS.A prediction model including 9 factors(age,pathological type,baseline NLR,baseline neutrophils,baseline IL-6,baseline monocytes,preoperative lymphocytes,preoperative SII,and preoperative LMR)was established for predicting the efficacy of neoadjuvant immunotherapy in NSCLC,with an AUC of 0.818.Conclusion:Neoadjuvant immunotherapy demonstrates favorable clinical efficacy in patients with NSCLC,particularly in those with squamous cell carcinoma.Meanwhile,peripheral blood inflammation-related indicators may serve as important biomarkers for predicting the efficacy and prognosis of neoadjuvant immunotherapy in NSCLC.
文摘BACKGROUND Hepatocellular carcinoma(HCC)remains a leading cause of cancer-related mortality worldwide.Despite improvements in surgical techniques and systemic therapies,long-term outcomes after liver resection are limited by high recurrence rates.While adjuvant strategies have shown limited benefit,the role of neoadjuvant immunotherapy in resectable HCC is still under investigation.AIM To assess the efficacy,feasibility,and safety of neoadjuvant immunotherapy in resectable HCC through a meta-analysis of current literature.METHODS A systematic search was conducted across PubMed,Web of Science,EMBASE,Cochrane Library,and Scopus for studies published in the past five years evaluating neoadjuvant immunotherapy in resectable HCC.Primary endpoints included major pathological response(MPR),pathological complete response(pCR),overall response rate(ORR),resection rate,and grade 3-4 treatment-related adverse events(TRAEs).A random-effects meta-analysis was conducted using log odds ratios(ORs)and pooled event rates were calculated to provide absolute estimates of clinical endpoints.RESULTS Twelve studies were included in the final analysis.The pooled ORs were 0.28(95%CI:0.19-0.41)for MPR,0.54(95%CI:0.25-1.14)for ORR,0.26(95%CI:0.11-0.66)for pCR,5.37(95%CI:2.70-10.66)for resection rate,and 0.33(95%CI:0.22-0.50)for grade 3-4 TRAEs.Corresponding pooled event rates were 19%for MPR,35%for ORR,22%for pCR,81%for resection feasibility,and 19%for severe TRAEs.CONCLUSION Neoadjuvant immunotherapy appears to be a feasible and safe approach in patients with resectable HCC,achieving moderate pathological responses and high resection rates.
基金supported by Open Foundation of Hubei Key Laboratory(China Three Gorges University)of Tumor Microenvironment and Immunotherapy(No.2022KZL1-08).
文摘Background:Lung cancer is a major public health concern,and postoperative rehabilitation is crucial for patients.With the emergence of neoadjuvant immunotherapy,understanding the home-based rehabilitation needs of postoperative lung cancer patients who have undergone this therapy has become important.Methods:This qualitative study employed grounded theory.Data were collected through face-to-face,in-depth,semi-structured interviews from February to June 2023 with 15 postoperative lung cancer patients who received routine neoadjuvant immunotherapy.Results:Five key themes emerged:(1)Limited exposure to home-based rehabilitation;(2)Unmet demand for home-based rehabilitation;(3)Factors hindering home-based rehabilitation;(4)Specific home-based rehabilitation needs;(5)Recommendations and observations.The findings revealed that patients lack awareness of home-based rehabilitation,have unmet rehabilitation needs,and require timely implementation of such programs to enhance rehabilitation management and quality of life.Conclusion:This study emphasizes the importance of developing and implementing home-based rehabilitation programs for lung cancer patients who have undergone neoadjuvant immunotherapy.These programs should address the identified needs and recommendations to improve rehabilitation outcomes and quality of life.Future efforts should focus on large-scale implementation and evaluation of these programs.
基金supported by grants from The National Natural Science Foundation of China(No.81771003 and 82071508).
文摘Temporal bone malignant tumors are characterized by atypical clinical symptoms,and easy recurrence and metastasis.They account for 0.2%of head and neck tumors,and the most common pathological type is squamous cell carcinoma.Patients with squamous cell carcinoma of the temporal bone are often at advanced stages when diagnosed,and lose the chance for surgery.Neoadjuvant immunotherapy has recently been approved as the first-line treatment for refractory recurrent/metastatic squamous cell carcinoma of the head and neck.However,it remains to be determined whether neoadjuvant immunotherapy can be used as the first-line treatment for temporal bone squamous cell carcinoma to reduce the tumor stage before surgery,or as a palliative treatment for patients with unresectable advanced stage carcinoma.The present study reviews the development of immunotherapy and its clinical application in head and neck squamous cell carcinoma,summarizes the treatment of temporal bone squamous cell carcinoma,and prospects the neoadjuvant immunotherapy as the first-line treatment for temporal bone squamous cell carcinoma.
基金supported by the National Key Research and Development Program of China(2021YFA0910100 and 2022YFC2504602)Healthy Zhejiang One Million People Cohort(K-20230085)+9 种基金National Natural Science Foundation of China(82304946,82241230,T2125002,82341007,82304946,82473489,and 82573745)Zhejiang gastrointestinal cancer Clinical Medical Research Center(2022E50006)Medical Science and Technology Project of Zhejiang Province(WKJ-ZJ-2323)Beijing Natural Science Foundation(Z220014)Natural Science Foundation of Zhejiang Province(LR21H280001,LBZ22H160002,LBD24H290001,and LMS25H160006)Science and Technology Projects of Zhejiang Province(2019C03049)Program of Zhejiang Provincial TCM Sci-tech Plan(2018ZY006 and 2020ZZ005)Science and Technology Projects of Zhejiang Province(2022KY684)Program of Zhejiang Provincial TCM Sci-tech Plan(2022ZQ020)the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ,and despite perioperative therapy plus D2 gastrectomy being the standard of care,long-term survival remains poor[3,4].
文摘BACKGROUND Neutrophil extracellular traps(NETs)are associated with an immunosuppressive tumor microenvironment and may influence the efficacy of immune-based therapies.However,their role in neoadjuvant chemotherapy combined with immunotherapy(NACI)for locally advanced gastric cancer(LAGC)remains unclear.AIM To investigate the prognostic and predictive value of NET density in LAGC patients undergoing NACI.METHODS We enrolled 31 LAGC patients treated with NACI.NET density was assessed through dual immunofluorescence staining of citrullinated histone H3 and myeloperoxidase in pretreatment biopsy and post-treatment surgical specimens.Patients were stratified into high and low pre-NACI NET groups based on median NET density.Pathological complete response(pCR)and overall response rates were evaluated in relation to NET density.Logistic regression analyses were performed to identify independent predictors of treatment outcomes.Dynamic changes in NET density during NACI were also analyzed.RESULTS Patients with low pre-NACI NET density demonstrated significantly higher rates of pCR(40%vs 6%,P=0.037)and overall response(53%vs 12%,P=0.023)compared to those with high NET density.Low pre-NACI NET density and higher programmed death protein ligand 1 expression were identified as independent protective factors for achieving pCR and better response rates.NACI increased NET density;however,this increase was primarily observed in non-pCR and nonresponder groups.Patients in the pCR and responder groups showed stable NET density before and after treatment.Higher post-NACI NET density was associated with poorer respond to NACI.High post-NACI NET density was associated with increased infiltration of immunosuppressive FOXP3+T regulatory cells(P=0.025)and CD68+macrophages(P=0.038).CONCLUSION Pre-NACI NET density serves as a prognostic and predictive biomarker for NACI efficacy in LAGC patients.Low pretreatment NET density is associated with favorable outcomes,while increased post-treatment NET density correlates with poorer response.Targeting NET formation may represent a novel therapeutic strategy to enhance NACI efficacy in LAGC.
基金Supported by the National Natural Science Foundation of China,No.82072732.
文摘BACKGROUND Endoscopy allows for the direct observation of primary tumor characteristics and responses after neoadjuvant treatment.However,reports on endoscopic evaluation following neoadjuvant immunotherapy remain limited.AIM To examine the predictive value of endoscopic findings of primary tumors for responses to neoadjuvant immunotherapy.METHODS This retrospective study,conducted at a tertiary center in China,evaluated 74 patients with colorectal cancer,including 17 with deficient mismatch repair(dMMR)and 15 with proficient mismatch repair(pMMR)tumors.Patients underwent neoadjuvant immunotherapy followed by surgery.Endoscopic findings before and after neoadjuvant immunotherapy were reviewed and compared with the pathology of the resected specimens.RESULTS In the pMMR group(n=57 evaluable patients),endoscopy identified 11/17 patients who achieved a complete response(CR),while misidentifying 1/40 patients with residual disease as CR(64.7%vs 2.5%,P<0.01).Conversely,22/40 patients with residual disease were accurately identified as achieving a partial response(PR),with 1/17 patients who achieved CR misclassified as PR(55.0%vs 5.9%,P<0.01).The sensitivity,specificity,and accuracy of endoscopic diagnosis for pathological CR were 64.7%,97.5%,and 87.7%,respectively.In the dMMR cohort,endoscopy classified 9/17 patients as CR and 2 of the remaining patients with residual tumors as PR(64.3%vs 66.7%,P=0.73).The method demonstrated 100%sensitivity and 82.4%accuracy in diagnosing pathological CR.CONCLUSION Endoscopic evidence of CR or PR was well correlated with postoperative pathological outcomes in the pMMR cohort.Despite endoscopic indications of tumor residue,a complete pathological response post-surgery was possible in the dMMR cohort.
基金supported by the National Natural Science Foundation of China[82073192,82273231]the Beijing Science and Technology Program[Z221100007422125]Both of the above-mentioned foundations provided financial support on data collection and statistical analysis.
文摘Background:The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy(MIG)for locally advanced gastric cancer(LAGC)remains controversial.This study aimed to compare short-term outcomes between MIG after neoadjuvant chemo-immunotherapy(NICT-MIG)and MIG after neoadjuvant chemotherapy alone(NCT-MIG),and determine risk factors for post-operative complications(POCs).Methods:This retrospective study included clinicopathologic data from 193 patients who underwent NCT-MIG or NICT-MIG between January 2020 and February 2023 in the Department of General Surgery,Chinese People’s Liberation Army General Hospital First Medical Center(Beijing,China).Propensity score-matched analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables and short-term outcomes were compared between the two groups.Results:The baseline characteristics were comparable between 49 patients in the NICT-MIG group and 86 patients in the NCT-MIG group after propensity score matching.Objective and pathologic complete response rates were significantly higher in the NICT-MIG group than in the NCT-MIG group(P<0.05).The overall incidence of treat-related adverse events,intraoperative bleeding,operation time,number of retrieved lymph nodes,time to the first flatus,post-operative duration of hospitalization,overall morbidity,and severe morbidity were comparable between the NCT-MIG and NICT-MIG groups(P>0.05).By multivariate logistic analysis,estimated blood loss of>200mL(P=0.010)and prognostic nutritional index(PNI)score of<45(P=0.003)were independent risk factors for POCs after MIG following neoadjuvant therapy.Conclusions:Safety and feasibility of NICT were comparable to those of NCT in patients undergoing MIG for LAGC.Patients with an estimated blood loss of>200mL or a PNI score of<45 should be carefully evaluated for increased POCs risk.
基金supported by the National Natural Science Foundation of China(Nos.82125001 and 82473368)the Innovation Program of Shanghai Municipal Education Commission(No.2023ZKZD33)Shanghai Pulmonary Hospital(Nos.FKCX2304 and FKLY20004).
文摘Immune checkpoint inhibitors(ICIs)have transformed the treatment landscape for resectable non-small cell lung cancer.Numerous trials have explored the use of ICIs,either as monotherapy or in combination with other therapies,in the neoadjuvant setting for stage Ⅰ-Ⅲ non-small cell lung cancer.Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy,with a high pathological response rate and significantly improved event-free survival.This review summarizes the findings of Phase Ⅰ-Ⅲ clinical trials investigating various neoadjuvant regimens,including ICI monotherapy,ICI therapy combined with chemother-apy,ICI plus anti-angiogenic therapy,dual ICI therapy,and ICI therapy in combination with radiotherapy or chemoradiotherapy.We discuss the benefits and outcomes associated with each approach.Despite the results being promising,several unresolved issues remain,including identification of reliable biomarkers,the appropri-ate duration of therapy,the optimal treatment regimen for tumors with high programmed cell death ligand 1(PD-L1)expression,the false-negative pathological complete response rate,and the role of digital pathology in assessing the response to treatment.Resistance to immunotherapy,in particular,remains a significant barrier to effective use of ICIs.Given the critical influence of the tumor microenvironment(TME)on the response to treat-ment,we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy.We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity,therapy-driven TME remodeling,and overcoming resistance to therapy.Finally,we propose future directions for advancements in personalized neoadjuvant immunotherapy.
文摘Despite existing curative options like surgical removal,tissue destruction techniques,and liver transplantation for early-stage hepatocellular carcinoma(HCC),the rising incidence and mortality rates of this global health burden necessitate continuous exploration of novel therapeutic strategies.This review critically assesses the dynamic treatment panorama for HCC,focusing specifically on the burgeoning role of immunotherapy in two key contexts:early-stage HCC and downstaging advanced HCC to facilitate liver transplant candidacy.It delves into the unique immunobiology of the liver and HCC,highlighting tumor-mediated immune evasion mechanisms.Analyzing the diverse immunothera-peutic approaches including checkpoint inhibitors,cytokine modulators,vaccines,oncolytic viruses,antigen-targeting antibodies,and adoptive cell therapy,this review acknowledges the limitations of current diagnostic markers alpha-fetoprotein and glypican-3 and emphasizes the need for novel biomarkers for patient selection and treatment monitoring.Exploring the rationale for neoadjuvant and adjuvant immunotherapy in early-stage HCC,current research is actively exploring the safety and effectiveness of diverse immunothera-peutic approaches through ongoing clinical trials.The review further explores the potential benefits and challenges of combining immunotherapy and liver transplant,highlighting the need for careful patient selection,meticulous monitoring,and novel strategies to mitigate post-transplant complications.Finally,this review delves into the latest findings from the clinical research landscape and future directions in HCC management,paving the way for optimizing treatment strategies and improving long-term survival rates for patients with this challenging malignancy.
基金supported by the grants from the National Natural Science Foundation of China(82273132 to Liu B).
文摘Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.
基金supported by the National Natural Science Foundation of China(82203786,82373231)the Natural Science Foundation of Liaoning Province of China(2022-YGJC-68,2023-BS-105)Chinese Young Breast Experts Research Project(CYBER-2021-A02,CYBER-2022-001).
文摘The optimal chemotherapy backbone and specific population of triple-negative breast cancer(TNBC)patients that benefit from neoadjuvant immunotherapy are not well established.This prospective,single-arm,phaseⅡTREND trial assessed the efficacy and safety of tislelizumab plus nab-paclitaxel and epirubicin/cyclophosphamide-based chemotherapy as a neoadjuvant treatment for TNBC(ChiCTR2000035262).The primary endpoint was pathological complete response(pCR),with the secondary endpoints including safety assessment and objective response rate(ORR).ScRNA-seq,bulk RNA-seq,TCR-seq,cyTOF and WES were performed on pre-treatment and post-treatment samples.Among 53 total enrolled patients,44 completed the combined neoadjuvant therapy,and 30 of 44 patients(68.18%)achieved pCR.Additionally,14 out of 44 patients had a complete response(31.82%),with an ORR of 93.18%.The most commonly observed treatment-related adverse events(TRAEs)were alopecia,nausea and liver injury with 6 cases classified as grade 3 or higher adverse events.Immune response-related pathways,including TNF signaling pathway,T cell receptor signaling pathway,were enriched in pCR group.Pre-treatment model was identified and construct to predict response to immunotherapy.CDKN1A+CD8 T lymphocytes were enriched in pCR group after neoadjuvant immunotherapy.Dynamic change of immune-related pathways at an early stage during the neoadjuvant immunotherapy may be associated with the treatment effcacy.In conclusion,neoadjuvant treatment of tislelizumab with nab-paclitaxel and anthracycline-based chemotherapy showed promising clinical activity and was well-tolerated among TNBC patients,without high incidence of TRAEs.These findings provide evidence supporting neoadjuvant tislelizumab with chemotherapy as an effective rational approach for treating TNBC.
基金supported by grants from the National Natural Science Foundation of China(Nos.82273129,82002451)the National Key Research and Development Program of China(No.2021YFC2500900)+3 种基金Beijing Nova Program(No.20230484267)the Chinese Academy of Medical Sciences Initiative for Innovative Medicine(Nos.2021-I2M-1-015,2024-I2M-C&T-C-008,2022-I2M-C&T-B-055,2022-I2M-C&T-B-060,2023-I2M-C&T-B-078)Central Health Research Key Projects(No.2022ZD17)Research Project of the Institute(No.LC2019L01).
文摘Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,patients’clinical outcomes with different regimens are uncertain.Our study aims to examine the efficacy of neoadjuvant immunotherapy(NAIT)for NSCLC patients and compare the overall survival(OS)and event-free survival(EFS)of patients receiving different NAT regimens.Methods:This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1,2016 and July 31,2022.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.Results:With a median follow-up of 27.5 months,the 1-year OS rates were 98.8%and 96.2%,and the 2-year OS rates were 96.6%and 85.8%in patients of the NAIT and neoadjuvant chemotherapy(NACT)group,respectively(hazard ratio[HR],0.339;95%confidence interval[CI],0.160-0.720;P=0.003).The 1-year EFS rates were 96.0%and 88.0%,and the 2-year EFS rates were 92.0%and 77.7%for patients in the NAIT and NACT groups,respectively(HR,0.438;95%CI,0.276-0.846;P=0.010).For patients who did not achieve pathological complete response(pCR),significantly longer OS(P=0.012)and EFS(P=0.019)were observed in patients receiving NAIT than those receiving NACT.Different NAT regimens had little effect on surgery and the postoperative length of stay(6[4,7]days vs.6[4,7]days,Z=-0.227,P=0.820).Conclusions:NAIT exhibited superior efficacy to NACT for NSCLC,resulting in longer OS and EFS.The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
基金supported by Shandong Provincial Natural Science Foundation(ZR2023LZL005)Jinan Science and Technology Development Foundation.
文摘Immunotherapy has become a standard treatment for patients with advanced urothelial carcinoma,and neoadjuvant immunotherapy is currently being extensively explored.This reviewhighlights the initial findings and key clinical therapeutic insights on immune checkpoint inhibitors in the early treatment of muscle-invasive bladder cancer across diverse patient populations.Most available literature consists of clinical investigations involving small sample,single-arm phase Ⅱ trials,with the primary endpoint being the pathologic complete response rate.Early results of immune checkpoint inhibitors in the neoadjuvant treatment of bladder cancer have demonstrated promising efficacy.However,these findings require confirmation in large phase Ⅲ clinical trials,with particular emphasis on long-term survival benefits and identifying patients who respond to treatment.
