Gastric cancer(GC)has remained one of the leading causes of cancer-related deaths globally.The development of noninvasive biomarkers in cancer diagnosis and treatment has gained substantial traction in recent years.Re...Gastric cancer(GC)has remained one of the leading causes of cancer-related deaths globally.The development of noninvasive biomarkers in cancer diagnosis and treatment has gained substantial traction in recent years.Recent evidence highlights hypercoagulation as a promising prognostic biomarker,particularly in locally advanced GC(LAGC)who underwent radical resection after neoadjuvant immunochemotherapy(NICT).A recent study by Li et al showed that hypercoagulation is a valuable prognostic indicator for patients with LAGC who have undergone radical resection following NICT.While the study addresses an important clinical issue and provides insightful findings,the present study offered valuable insights;the applicability of these findings was constrained by the retrospective design,the focus on a single center,and the small sample size of the existing studies.Additionally,vital confounders,such as preoperative comorbidities and systemic inflammation,are inadequately addressed.Future studies should focus on prospective multicenter trials,incorporating advanced predictive models such as machine learning algorithms to integrate coagulation markers with other clinical variables for personalized risk stratification.In addition,we are required to validate findings to examine the biological mechanisms correlating hypercoagulation to tumor progression.Integrating machine learning,comprehensive biomarker panels,and real-world data would allow the researchers to have personalized risk stratification,improve predictive accuracy,and optimize clinical decision-making.Finally,A multidisciplinary approach,including lifestyle interventions and imaging modalities,is essential to improve outcomes among patients with GC.展开更多
BACKGROUND Coagulation status is closely related to the progression of malignant tumors.In the era of neoadjuvant immunochemotherapy(NICT),the prognostic utility of coagulation indicators in patients with locally adva...BACKGROUND Coagulation status is closely related to the progression of malignant tumors.In the era of neoadjuvant immunochemotherapy(NICT),the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer(LAGC)undergoing new treatments remains to be determined.AIM To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT.METHODS A retrospective analysis of clinical data from 104 patients with LAGC,who underwent radical resection after NICT between 2020 and 2023,was performed.Ddimer and fibrinogen concentrations were measured one week before NICT,and again one week before surgery,to analyze the association between these two indicators and their combined indices[non-hypercoagulation(D-dimer and fibrinogen concentrations within the upper limit of normal)vs hypercoagulation(D-dimer or fibrinogen concentrations above the upper limit of normal)]with prognosis.After radical resection,patients were followed-up periodically.The median follow-up duration was 21 months.RESULTS Data collected after NICT revealed that the three-year overall survival(OS)and disease-free survival(DFS)rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group[94.4%vs 78.0%(P=0.019)and 87.0%vs 68.0%(P=0.027),respectively].Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS[hazard ratio(HR)4.436,P=0.023]and DFS(HR 2.551,P=0.039).Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups(88.3%vs 84.1%,respectively;P=0.443).CONCLUSION Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.展开更多
There is no standard treatment for patients with locally advanced gastric cancer(LAGC).Neoadjuvant immunochemotherapy(NICT)is an emerging therapeutic strategy in LAGC.The prognosis of patients undergoing NICT plus rad...There is no standard treatment for patients with locally advanced gastric cancer(LAGC).Neoadjuvant immunochemotherapy(NICT)is an emerging therapeutic strategy in LAGC.The prognosis of patients undergoing NICT plus radical surgery varies.Hypercoagulation is frequently identified in cancer patients.A retrospective study by Li et al confirmed that in LAGC patients undergoing radical resection post-NICT,elevated D-dimer and fibrinogen levels were asso-ciated with poor prognosis,and their combined assessment improved predictive accuracy.This retrospective study has some limitations,and further prospective research is required to validate hypercoagulation as a prognostic indicator and develop a more precise predictive model.Establishing such a model can facilitate personalized treatment strategies for patients with LAGC.展开更多
BACKGROUND Neoadjuvant immunochemotherapy(nICT)has emerged as a popular treatment approach for advanced gastric cancer(AGC)in clinical practice worldwide.However,the response of AGC patients to nICT displays significa...BACKGROUND Neoadjuvant immunochemotherapy(nICT)has emerged as a popular treatment approach for advanced gastric cancer(AGC)in clinical practice worldwide.However,the response of AGC patients to nICT displays significant heterogeneity,and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes.AIM To establish a radiomic model to predict the response of AGC patients to nICT.METHODS Patients with AGC who received nICT(n=60)were randomly assigned to a training cohort(n=42)or a test cohort(n=18).Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT.An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature.The performance of all the models was assessed through receiver operating characteristic curve analysis,decision curve analysis(DCA)and the Hosmer Lemeshow goodness-of-fit test.RESULTS The radiomic nomogram could accurately predict the response of AGC patients to nICT.In the test cohort,the area under curve was 0.893,with a 95%confidence interval of 0.803-0.991.DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models.CONCLUSION A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC.This tool can assist clinicians in treatment-related decision-making.展开更多
BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell ca...BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.展开更多
The role of the gut microbiome in enhancing the efficacy of anticancer treatments like chemotherapy and radiotherapy is well acknowledged.However,there is limited empirical evidence on its predictive capabilities for ...The role of the gut microbiome in enhancing the efficacy of anticancer treatments like chemotherapy and radiotherapy is well acknowledged.However,there is limited empirical evidence on its predictive capabilities for neoadjuvant immunochemotherapy(NICT)responses in esophageal squamous cell carcinoma(ESCC).Our study fills this gap by comprehensively analyzing the gut microbiome's influence on NICT outcomes.We analyzed 16S rRNA gene sequences from 136 fecal samples from 68 ESCC patients before and after NICT,along with 19 samples from healthy controls.After NICT,marked microbiome composition changes were noted,including a decrease in EScC-associated pathogens and an increase in beneficial microbes such as Limosilactobacillus,Lacticaseibacillus,and Staphylococcus.Baseline microbiota profiles effectively differentiated responders from nonresponders,with responders showing higher levels of short-chain fatty acid(SCFA)-producing bacteria such as Faecalibacterium,Eubacterium_eligens_group,Anaerostipes,and Odoribacter,and nonresponders showing increases in Veillonella,Campylobacter,Atopobium,and Trichococcus.We then divided our patient cohort into training and test sets at a 4:1 ratio and utilized the XGBoost-RFE algorithm to identify 7 key microbial biomarkers-Faecalibacterium,Subdoligranulum,Veillonella,Hungatella,Odoribacter,Butyricicoccus,and HTO02.Apredictive model was developed using LightGBM,which achieved an area under the receiver operating characteristic curve(AUC)of 86.8%[95%confidence interval(CI).73.8%to 99.4%] in the training set,76.8%(95%Cl,41.2%to 99.7%)in the validation set,and 76.5%(95%Cl,50.4%to 100%)in the testing set.Our findings underscore the gut microbiome as a novel source of biomarkers for predicting NICT responses in ESCc,highlighting its potential to enhance personalized treatment strategies and advance the integration of microbiome profiling into clinical practice for modulating cancer treatment responses.展开更多
The clinical benefit of neoadjuvant immunochemotherapy in locally advanced cervical cancer(LAcC)remains unclear.This singlearm,phase Ⅱ study(Chinese Clinical Trial Registry,ChiCTR2200065392)aimed to evaluate the effi...The clinical benefit of neoadjuvant immunochemotherapy in locally advanced cervical cancer(LAcC)remains unclear.This singlearm,phase Ⅱ study(Chinese Clinical Trial Registry,ChiCTR2200065392)aimed to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death protein 1(PD-1)antibody tislelizumab in combination with chemotherapy in treatment-naive patients with stage IB3/IIA2 LACC.Enrolled patients received tislelizumab(200 mg,every 3 weeks)plus chemotherapy for 3 cycles before radical surgery.The primary endpoint was the pathological complete response(pCR).Secondary endpoints were objective response rate(ORR)per Response Evaluation Criteria in Solid Tumors version 1.1,disease-free survival,overall survival,and safety.Exploratory endpoints included tissue-based and blood-based biomarkers to identify the biological drivers behind the clinical outcomes.Between November 2022 and March 2024,30 patients were enrolled.All patients completed 3 cycles of neoadjuvant immunochemotherapy and underwent radical surgery.The pCR was observed in 20(66.7%)patients,and 4(13.3%)patients achieved major pathological response(MPR),with an optimal pathological response rate(OPR)of 80.0%.The ORR was 90.0%,with 17(56.7%)complete responses.Survival data were immature at the median follow-up of 14.7 months(data cutoff,December 31,2024).Grade 3 treatment-related adverse events(TRAEs)and immune-related AEs occurred in 26.7%and 3.3%of patients,respectively.No treatment-related death occurred.Patients with pCR had significantly higher expression of PD-L1 CPS at baseline,and a strong relationship with immune-related signature(all p<0.05).Neoadjuvant tislelizumab plus chemotherapy showed promising antitumor efficacy and a well-tolerated safety profle in patients with stage IB3/IIA2 LACC,and might be a potential option in this population.展开更多
Background:In the era of immunotherapy,neoadjuvant immunochemotherapy(NAIC)for the treatment of locally advanced esophageal squamous cell carcinoma(ESCC)is used clinically but lacks of high-level clinical evidence.Thi...Background:In the era of immunotherapy,neoadjuvant immunochemotherapy(NAIC)for the treatment of locally advanced esophageal squamous cell carcinoma(ESCC)is used clinically but lacks of high-level clinical evidence.This study aimed to compare the safety and long-term efficacy of NAIC followed byminimally invasive esophagectomy(MIE)with those of neoadjuvant chemotherapy(NAC)followed by MIE.Methods:A prospective,single-center,open-label,randomized phase Ⅲ clinical trial was conducted at Henan Cancer Hospital,Zhengzhou,China.Patients were randomly assigned to receive either neoadjuvant toripalimab(240mg)plus paclitaxel(175 mg/m^(2))+cisplatin(75 mg/m^(2))(toripalimab group)or paclitaxel+cisplatin alone(chemotherapy group)every 3 weeks for 2 cycles.After surgery,the toripalimab group received toripalimab(240 mg every 3 weeks for up to 6 months).The primary endpoint was event-free survival(EFS).The pathological complete response(pCR)and overall survival(OS)were key secondary endpoints.Adverse events(AEs)and quality of life were also assessed.Results:Between May 15,2020 and August 13,2021,252 ESCC patients ranging fromT1N1-3M0 to T2-3N0-3M0were enrolled for interim analysis,with 127 in the toripalimab group and 125 in the chemotherapy group.The 1-year EFS rate was 77.9%in the toripalimab group compared to 64.3%in the chemotherapy group(hazard ratio[HR]=0.62;95%confidence interval[CI]=0.39 to 1.00;P=0.05).The 1-year OS rates were 94.1%and 83.0%in the toripalimab and chemotherapy groups,respectively(HR=0.48;95%CI=0.24 to 0.97;P=0.037).The patients in the toripalimab group had a higher pCR rate(18.6%vs.4.6%;P=0.001).The rates of postoperative Clavien-Dindo grade Ⅲb or higher morbidity were 9.8%in the toripalimab group and 6.8%in the chemotherapy group,with no significant difference observed(P=0.460).The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups(12.5%versus 12.4%).Conclusions:The interim results of this ongoing trial showed that in resectable ESCC,the addition of perioperative toripalimab to NAC is safe,may improve OS and might change the standard treatment in the future.展开更多
文摘Gastric cancer(GC)has remained one of the leading causes of cancer-related deaths globally.The development of noninvasive biomarkers in cancer diagnosis and treatment has gained substantial traction in recent years.Recent evidence highlights hypercoagulation as a promising prognostic biomarker,particularly in locally advanced GC(LAGC)who underwent radical resection after neoadjuvant immunochemotherapy(NICT).A recent study by Li et al showed that hypercoagulation is a valuable prognostic indicator for patients with LAGC who have undergone radical resection following NICT.While the study addresses an important clinical issue and provides insightful findings,the present study offered valuable insights;the applicability of these findings was constrained by the retrospective design,the focus on a single center,and the small sample size of the existing studies.Additionally,vital confounders,such as preoperative comorbidities and systemic inflammation,are inadequately addressed.Future studies should focus on prospective multicenter trials,incorporating advanced predictive models such as machine learning algorithms to integrate coagulation markers with other clinical variables for personalized risk stratification.In addition,we are required to validate findings to examine the biological mechanisms correlating hypercoagulation to tumor progression.Integrating machine learning,comprehensive biomarker panels,and real-world data would allow the researchers to have personalized risk stratification,improve predictive accuracy,and optimize clinical decision-making.Finally,A multidisciplinary approach,including lifestyle interventions and imaging modalities,is essential to improve outcomes among patients with GC.
基金Natural Science Foundation of Hubei Province of China,No.2024AFB655Key Research and Development Program of Hubei Province of China,No.2021BCA116National Natural Science Foundation of China,No.82072736,No.82003205,No.
文摘BACKGROUND Coagulation status is closely related to the progression of malignant tumors.In the era of neoadjuvant immunochemotherapy(NICT),the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer(LAGC)undergoing new treatments remains to be determined.AIM To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT.METHODS A retrospective analysis of clinical data from 104 patients with LAGC,who underwent radical resection after NICT between 2020 and 2023,was performed.Ddimer and fibrinogen concentrations were measured one week before NICT,and again one week before surgery,to analyze the association between these two indicators and their combined indices[non-hypercoagulation(D-dimer and fibrinogen concentrations within the upper limit of normal)vs hypercoagulation(D-dimer or fibrinogen concentrations above the upper limit of normal)]with prognosis.After radical resection,patients were followed-up periodically.The median follow-up duration was 21 months.RESULTS Data collected after NICT revealed that the three-year overall survival(OS)and disease-free survival(DFS)rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group[94.4%vs 78.0%(P=0.019)and 87.0%vs 68.0%(P=0.027),respectively].Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS[hazard ratio(HR)4.436,P=0.023]and DFS(HR 2.551,P=0.039).Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups(88.3%vs 84.1%,respectively;P=0.443).CONCLUSION Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.
文摘There is no standard treatment for patients with locally advanced gastric cancer(LAGC).Neoadjuvant immunochemotherapy(NICT)is an emerging therapeutic strategy in LAGC.The prognosis of patients undergoing NICT plus radical surgery varies.Hypercoagulation is frequently identified in cancer patients.A retrospective study by Li et al confirmed that in LAGC patients undergoing radical resection post-NICT,elevated D-dimer and fibrinogen levels were asso-ciated with poor prognosis,and their combined assessment improved predictive accuracy.This retrospective study has some limitations,and further prospective research is required to validate hypercoagulation as a prognostic indicator and develop a more precise predictive model.Establishing such a model can facilitate personalized treatment strategies for patients with LAGC.
基金Supported by the Affiliated Hospital of Qingdao University Horizontal Fund,No.3635Intramural Project Fund,No.4618.
文摘BACKGROUND Neoadjuvant immunochemotherapy(nICT)has emerged as a popular treatment approach for advanced gastric cancer(AGC)in clinical practice worldwide.However,the response of AGC patients to nICT displays significant heterogeneity,and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes.AIM To establish a radiomic model to predict the response of AGC patients to nICT.METHODS Patients with AGC who received nICT(n=60)were randomly assigned to a training cohort(n=42)or a test cohort(n=18).Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT.An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature.The performance of all the models was assessed through receiver operating characteristic curve analysis,decision curve analysis(DCA)and the Hosmer Lemeshow goodness-of-fit test.RESULTS The radiomic nomogram could accurately predict the response of AGC patients to nICT.In the test cohort,the area under curve was 0.893,with a 95%confidence interval of 0.803-0.991.DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models.CONCLUSION A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC.This tool can assist clinicians in treatment-related decision-making.
文摘BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.
基金supported by the National Nature Science Foundation of China(nos.82303178 and 82200612)the Shenzhen Science and Technology Program(grant nos.JCYJ20220530154012028 and RCBS20221008093243060)the Guangdong Basic and Applied Basic Research Foundation(no.2021A1515110216).
文摘The role of the gut microbiome in enhancing the efficacy of anticancer treatments like chemotherapy and radiotherapy is well acknowledged.However,there is limited empirical evidence on its predictive capabilities for neoadjuvant immunochemotherapy(NICT)responses in esophageal squamous cell carcinoma(ESCC).Our study fills this gap by comprehensively analyzing the gut microbiome's influence on NICT outcomes.We analyzed 16S rRNA gene sequences from 136 fecal samples from 68 ESCC patients before and after NICT,along with 19 samples from healthy controls.After NICT,marked microbiome composition changes were noted,including a decrease in EScC-associated pathogens and an increase in beneficial microbes such as Limosilactobacillus,Lacticaseibacillus,and Staphylococcus.Baseline microbiota profiles effectively differentiated responders from nonresponders,with responders showing higher levels of short-chain fatty acid(SCFA)-producing bacteria such as Faecalibacterium,Eubacterium_eligens_group,Anaerostipes,and Odoribacter,and nonresponders showing increases in Veillonella,Campylobacter,Atopobium,and Trichococcus.We then divided our patient cohort into training and test sets at a 4:1 ratio and utilized the XGBoost-RFE algorithm to identify 7 key microbial biomarkers-Faecalibacterium,Subdoligranulum,Veillonella,Hungatella,Odoribacter,Butyricicoccus,and HTO02.Apredictive model was developed using LightGBM,which achieved an area under the receiver operating characteristic curve(AUC)of 86.8%[95%confidence interval(CI).73.8%to 99.4%] in the training set,76.8%(95%Cl,41.2%to 99.7%)in the validation set,and 76.5%(95%Cl,50.4%to 100%)in the testing set.Our findings underscore the gut microbiome as a novel source of biomarkers for predicting NICT responses in ESCc,highlighting its potential to enhance personalized treatment strategies and advance the integration of microbiome profiling into clinical practice for modulating cancer treatment responses.
基金supported by the 358 program Clinical Trial Fund of Tianjin Cancer Hospital(Grant No.TZ3582023-010)the National Natural Science Foundation of China(Grant No.82202863)。
文摘The clinical benefit of neoadjuvant immunochemotherapy in locally advanced cervical cancer(LAcC)remains unclear.This singlearm,phase Ⅱ study(Chinese Clinical Trial Registry,ChiCTR2200065392)aimed to evaluate the efficacy and safety of neoadjuvant anti-programmed cell death protein 1(PD-1)antibody tislelizumab in combination with chemotherapy in treatment-naive patients with stage IB3/IIA2 LACC.Enrolled patients received tislelizumab(200 mg,every 3 weeks)plus chemotherapy for 3 cycles before radical surgery.The primary endpoint was the pathological complete response(pCR).Secondary endpoints were objective response rate(ORR)per Response Evaluation Criteria in Solid Tumors version 1.1,disease-free survival,overall survival,and safety.Exploratory endpoints included tissue-based and blood-based biomarkers to identify the biological drivers behind the clinical outcomes.Between November 2022 and March 2024,30 patients were enrolled.All patients completed 3 cycles of neoadjuvant immunochemotherapy and underwent radical surgery.The pCR was observed in 20(66.7%)patients,and 4(13.3%)patients achieved major pathological response(MPR),with an optimal pathological response rate(OPR)of 80.0%.The ORR was 90.0%,with 17(56.7%)complete responses.Survival data were immature at the median follow-up of 14.7 months(data cutoff,December 31,2024).Grade 3 treatment-related adverse events(TRAEs)and immune-related AEs occurred in 26.7%and 3.3%of patients,respectively.No treatment-related death occurred.Patients with pCR had significantly higher expression of PD-L1 CPS at baseline,and a strong relationship with immune-related signature(all p<0.05).Neoadjuvant tislelizumab plus chemotherapy showed promising antitumor efficacy and a well-tolerated safety profle in patients with stage IB3/IIA2 LACC,and might be a potential option in this population.
基金Central Plains Young Top Talent,Grant/Award Number:2022Henan Province Medical Science and Technology Key Projects Coconstructed by the Ministry of Health,Grant/Award Number:SBGJ202102059+2 种基金Wu Jieping Medical Foundation,Grant/Award Number:320.6750.2020-15-1Henan Province Health Science and Technology Innovation Outstanding Young Talent Training Project,Grant/Award Number:YXKC2021029National Natural Science Foundation of China,Grant/Award Number:82002521。
文摘Background:In the era of immunotherapy,neoadjuvant immunochemotherapy(NAIC)for the treatment of locally advanced esophageal squamous cell carcinoma(ESCC)is used clinically but lacks of high-level clinical evidence.This study aimed to compare the safety and long-term efficacy of NAIC followed byminimally invasive esophagectomy(MIE)with those of neoadjuvant chemotherapy(NAC)followed by MIE.Methods:A prospective,single-center,open-label,randomized phase Ⅲ clinical trial was conducted at Henan Cancer Hospital,Zhengzhou,China.Patients were randomly assigned to receive either neoadjuvant toripalimab(240mg)plus paclitaxel(175 mg/m^(2))+cisplatin(75 mg/m^(2))(toripalimab group)or paclitaxel+cisplatin alone(chemotherapy group)every 3 weeks for 2 cycles.After surgery,the toripalimab group received toripalimab(240 mg every 3 weeks for up to 6 months).The primary endpoint was event-free survival(EFS).The pathological complete response(pCR)and overall survival(OS)were key secondary endpoints.Adverse events(AEs)and quality of life were also assessed.Results:Between May 15,2020 and August 13,2021,252 ESCC patients ranging fromT1N1-3M0 to T2-3N0-3M0were enrolled for interim analysis,with 127 in the toripalimab group and 125 in the chemotherapy group.The 1-year EFS rate was 77.9%in the toripalimab group compared to 64.3%in the chemotherapy group(hazard ratio[HR]=0.62;95%confidence interval[CI]=0.39 to 1.00;P=0.05).The 1-year OS rates were 94.1%and 83.0%in the toripalimab and chemotherapy groups,respectively(HR=0.48;95%CI=0.24 to 0.97;P=0.037).The patients in the toripalimab group had a higher pCR rate(18.6%vs.4.6%;P=0.001).The rates of postoperative Clavien-Dindo grade Ⅲb or higher morbidity were 9.8%in the toripalimab group and 6.8%in the chemotherapy group,with no significant difference observed(P=0.460).The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups(12.5%versus 12.4%).Conclusions:The interim results of this ongoing trial showed that in resectable ESCC,the addition of perioperative toripalimab to NAC is safe,may improve OS and might change the standard treatment in the future.
