Objective:The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods:A total of 196 eligible pat...Objective:The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods:A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023.Functional MR was performed at baseline and after one cycle of chemotherapy.The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package.The initial 100 cases were designated as the training set,the following 48 cases were designated as the validation set,and the final 48 cases were designated as the intervention validation set.Results:Good performance for the response prediction(AUC=0.818 in the training set and 0.755 in the validation set)was demonstrated.The objective response rates(ORRs)in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets.Worse progression-free survival and overall survival rates were noted in the high-risk population.In the intervention set 22.9%(11/48)of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1%(37/48),which was significantly higher than the training and validation sets[47.97%(71/148);P=0.000].Conclusions:A functional MR signature effectively predicted the chemotherapy response and long-term survival.The adjustment of the regimen guided by the model significantly improved the ORR.展开更多
The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point f...The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.展开更多
Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Method...Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Methods： Univadate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results： The most frequent severe toxicities （Grade 3/4） were as follows： neutropenia （27.4%）, diarrhea （16.9%）, leucopenia （12.6%）, vomiting （3.2%） and thrombocytopenia （2.1%）. Thrombocytosis was observed in 25 （26.3%） patients. ORR was 25.3%. Thrombocytopenia （P = 0.014）, line of chemotherapy （P = 0.028） and thrembocytosis （P = 0.033） were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia （odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705-43.385, P = 0.009） and first line chemotherapy （OR = 5.155, 95% CI = 1.153-23.256, P = 0.032） positively related to ORR. Conclusion： Threm- bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ- ated with ORR.展开更多
BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as...BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.展开更多
BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplati...BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
BACKGROUND Transarterial chemoembolization(TACE)is a recommended treatment for patients with intermediate stage hepatocellular carcinoma(HCC)but with variable treatment outcomes.AIM To determine factors for predicting...BACKGROUND Transarterial chemoembolization(TACE)is a recommended treatment for patients with intermediate stage hepatocellular carcinoma(HCC)but with variable treatment outcomes.AIM To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC.METHODS Patients with Barcelona Clinic Liver Cancer(BCLC)stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009.Patients were assigned to either the objective responder(OR)group or the non-OR group according to mRECIST criteria.Clinical and radiological characteristics were compared between the 2 groups.The overall survival of enrolled subjects was analyzed.RESULTS In 128 enrolled patients,66(51.6%)were in the OR group and 62(48.4%)in the non-OR group.Compared with the non-OR group,the OR group had a significantly smaller HCC size(6.55 cm vs 9.50 cm,P=0.001)and was within the up-to-7 criteria(50%vs 26.7%,P=0.001).After multivariable analyses,these significant associations still existed.Overall survival rate of all the subjects averaged 20.65±13.26 mo.The survival rate at 1-year was 64.8%,2-year was 46.9%,and 3-year was 31.2%.For those patients with OR to TACE,smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival.Those patients with subgroup B1 had the highest OR ratio(75%)and better overall survival(26.70±12.07 mo)after TACE.CONCLUSION BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE.BCLC stage B subgroup is useful to predict refractoriness to TACE.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
Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximab...Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximabβ(CMAB009),as a modified antibody of cetuximab,prospectively selected for dual RAS/BRAF wild-type patients,has not yet been validated in the Chinese mCRC patients through phase 3 trial.In this study(ClinicalTrials.gov identifier:NCT03206151),patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximabβplus FOLFIRI or FOLFIRI alone.The primary endpoint was blinded independent review committee-assessed progression-free survival(PFS).The secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),surgery rate for metastasis and R0 resection rate,and safety.From January 4,2018 to September 2,2021,a total of 505 eligible patients were enrolled and received study treatment;the median follow-up duration was 8.7 months(95%confidence interval[Cl],7.77 to 9.29)and 5.9 months(95%CI,5.63 to 6.65)in cetuximabβplus FOLFIRI group and FOLFIRI group,respectively.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI demonstrated statistically significant improvements in median PFS(13.1 vs.9.6 months,hazard ratio[HR],0.639;95%CI,0.468 to 0.872;P=0.004),median OS(28.3 vs.23.1 months,HR,0.729;95%CI,0.551 to 0.965;P=0.024),and ORR(69.1%vs.42.3%,odds ratio,3.090;95%CI,2.280 to 4.189;P<0.001).Cetuximabβplus FOLFIRI exhibited manageable toxicity without novel safety signals.This study demonstrated that cetuximabβplus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profle,offering a new treatment option for this patient population.展开更多
Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into t...Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).展开更多
Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been es...Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.展开更多
Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy amo...Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.展开更多
This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APIC...This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APICAL-CRC ClinicalTrials.gov number,NCT04271813).Between June 2020 and September 2023,a total of 30 patients were eventually enrolled and received the study regimen.Among these 30 patients,50%had an Eastern Cooperative Oncology Group(ECOG)score of 0–1,and the other 50%had a score of 2.The objective response rates(ORRs)were 48.3%(95%CI 29.4–67.5)in the efficacy-evaluable cohort and 46.7%(95%CI 28.3–65.7)in the intent-to-treat(ITT)cohort.Twelve patients had stable disease,and the disease control rates(DCRs)were 89.7%(95%CI 72.6–97.8)and 86.7%(95%CI 69.3–96.2)in the efficacy-evaluable and ITT cohorts,respectively.The median progressionfree survival(mPFS)was 8.6 months(95%CI 4.8–11.0),and the median overall survival(mOS)reached 22.9 months(95%CI 13.5–36.3).Treatment-related adverse events(TRAEs)of any grade were reported in 23 patients(76.7%),and grade 3 TRAEs occurred in 4 patients(13.3%).Multivariate Cox regression analysis revealed that the presence of liver metastases was an independent prognostic factor for poor PFS(HR=5.66,95%CI 1.58–20.2)and OS(HR=7.85,95%CI 1.38–44.8),whereas FLT mutation was independently associated with poor OS(HR=12.5,95%CI 1.54–101).This trial demonstrated that sintilimab plus anlotinib exhibited promising antitumor efficacy along with a manageable safety profile among treatment-naïve mCRC patients.展开更多
The objective response rate of conventional transarterial chemoembolization(TACE)for locoregional control of hepatocellular carcinoma(HCC)is approximately 50%.We previously developed bicarbonate-integrated TACE,termed...The objective response rate of conventional transarterial chemoembolization(TACE)for locoregional control of hepatocellular carcinoma(HCC)is approximately 50%.We previously developed bicarbonate-integrated TACE,termed TILA-TACE,which demonstrated 100%effectiveness for locoregional control of unresectable HCC.This study aimed to validate its efficacy,selectivity,and safety in real-world clinical practice(ChiCTR-ONC-17013416).A total of 413 patients were enrolled,including 40(9.7%)with early-stage HCC,29(7.0%)with intermediate-stage HCC,and 344(83.3%)with advanced-stage HCC.Primary tumors and macrovascular invasion/extrahepatic metastases were treated with TILA-TACE and radiation therapy,respectively.The side effects of TILA-TACE were recorded.The objective response rate of HCC tumors to TILA-TACE was 99.01%,including a complete response in 72.77%of patients.The objective response rate of tumor thrombus to radiation therapy was 96.88%.During a median follow-up of 38 months,there were 1 and 4 deaths among early-and intermediate-stage patients,respectively.The median survival of advanced-stage patients was 27 months.We found that intrahepatic metastases accounted for 70.4%(107/152)of cancer-related deaths after effective control of primary tumors and vascular invasion.The main adverse events associated with TILA-TACE were transient liver enzyme or bilirubin abnormalities(86.44%and 56.66%,respectively),which was consistent with the known sideeffect profile of TACE.In conclusion,TILA-TACE is a novel and highly effective treatment for the local control of HCC with a tolerable safety profile.When combined with radiation therapy for macrovascular invasion,it offers significant survival benefits for patients with advanced HCC.展开更多
基金supported by the National Natural Science Foundation of China(Grant nos.82271946 and 82202101)Innovative Achievement Transformation of Shenkang MedicalEnterprise Integration(Grant no.SHDC2023CRD014)。
文摘Objective:The aim of the study was to evaluate the feasibility of functional MR in predicting the clinical response to chemotherapy in patients with colorectal liver metastases(CLM).Methods:A total of 196 eligible patients were enrolled in the study between August 2016 and January 2023.Functional MR was performed at baseline and after one cycle of chemotherapy.The diffusion kurtosis radiomic texture features were extracted and a signature model was built using the R package.The initial 100 cases were designated as the training set,the following 48 cases were designated as the validation set,and the final 48 cases were designated as the intervention validation set.Results:Good performance for the response prediction(AUC=0.818 in the training set and 0.755 in the validation set)was demonstrated.The objective response rates(ORRs)in the high-risk subgroup were significantly lower than the low-risk subgroup in the training and validation sets.Worse progression-free survival and overall survival rates were noted in the high-risk population.In the intervention set 22.9%(11/48)of the chemotherapy regimens for patients were changed in response to the model-predicted results and the ORR reached 77.1%(37/48),which was significantly higher than the training and validation sets[47.97%(71/148);P=0.000].Conclusions:A functional MR signature effectively predicted the chemotherapy response and long-term survival.The adjustment of the regimen guided by the model significantly improved the ORR.
文摘The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
基金Supported by grants from the Key Project of Hubei Provincial Health Office (No. JX5A01)Wuhan Planning Project of Science and Technology (No. 201161038339-07)
文摘Objective： The aim of our study was to investigate if common toxicities are correlated to objective response rate （ORR） in metastatic colorectal cancer （mCRC） patients treated by irinotecan based regimens. Methods： Univadate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results： The most frequent severe toxicities （Grade 3/4） were as follows： neutropenia （27.4%）, diarrhea （16.9%）, leucopenia （12.6%）, vomiting （3.2%） and thrombocytopenia （2.1%）. Thrombocytosis was observed in 25 （26.3%） patients. ORR was 25.3%. Thrombocytopenia （P = 0.014）, line of chemotherapy （P = 0.028） and thrembocytosis （P = 0.033） were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia （odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705-43.385, P = 0.009） and first line chemotherapy （OR = 5.155, 95% CI = 1.153-23.256, P = 0.032） positively related to ORR. Conclusion： Threm- bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ- ated with ORR.
文摘BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment options.AIM To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic BTCs.METHODS This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical University.Eligible patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease progression.The primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and safety.RESULTS A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were females.Tumor response assessment was impeded for one patient due to premature demise from tumor hemorrhage.Among the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were documented.CONCLUSION Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.
文摘BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
文摘BACKGROUND Transarterial chemoembolization(TACE)is a recommended treatment for patients with intermediate stage hepatocellular carcinoma(HCC)but with variable treatment outcomes.AIM To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC.METHODS Patients with Barcelona Clinic Liver Cancer(BCLC)stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009.Patients were assigned to either the objective responder(OR)group or the non-OR group according to mRECIST criteria.Clinical and radiological characteristics were compared between the 2 groups.The overall survival of enrolled subjects was analyzed.RESULTS In 128 enrolled patients,66(51.6%)were in the OR group and 62(48.4%)in the non-OR group.Compared with the non-OR group,the OR group had a significantly smaller HCC size(6.55 cm vs 9.50 cm,P=0.001)and was within the up-to-7 criteria(50%vs 26.7%,P=0.001).After multivariable analyses,these significant associations still existed.Overall survival rate of all the subjects averaged 20.65±13.26 mo.The survival rate at 1-year was 64.8%,2-year was 46.9%,and 3-year was 31.2%.For those patients with OR to TACE,smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival.Those patients with subgroup B1 had the highest OR ratio(75%)and better overall survival(26.70±12.07 mo)after TACE.CONCLUSION BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE.BCLC stage B subgroup is useful to predict refractoriness to TACE.
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.
文摘Cetuximab plus irinotecan,fluorouracil,and leucovorin(FOLFIRI)represents a first-line therapeutic standard for RAS/BRAF wild-type metastatic colorectal cancer(mCRC)patients.Despite this established approach,cetuximabβ(CMAB009),as a modified antibody of cetuximab,prospectively selected for dual RAS/BRAF wild-type patients,has not yet been validated in the Chinese mCRC patients through phase 3 trial.In this study(ClinicalTrials.gov identifier:NCT03206151),patients with RAS/BRAF wild-type mCRC who were not suitable for radical resection were randomly assigned in a 1:1 ratio to receive cetuximabβplus FOLFIRI or FOLFIRI alone.The primary endpoint was blinded independent review committee-assessed progression-free survival(PFS).The secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),surgery rate for metastasis and R0 resection rate,and safety.From January 4,2018 to September 2,2021,a total of 505 eligible patients were enrolled and received study treatment;the median follow-up duration was 8.7 months(95%confidence interval[Cl],7.77 to 9.29)and 5.9 months(95%CI,5.63 to 6.65)in cetuximabβplus FOLFIRI group and FOLFIRI group,respectively.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI demonstrated statistically significant improvements in median PFS(13.1 vs.9.6 months,hazard ratio[HR],0.639;95%CI,0.468 to 0.872;P=0.004),median OS(28.3 vs.23.1 months,HR,0.729;95%CI,0.551 to 0.965;P=0.024),and ORR(69.1%vs.42.3%,odds ratio,3.090;95%CI,2.280 to 4.189;P<0.001).Cetuximabβplus FOLFIRI exhibited manageable toxicity without novel safety signals.This study demonstrated that cetuximabβplus FOLFIRI provided significant clinical benefits as a first-line treatment for patients with RAS/BRAF wild-type mCRC.Compared to FOLFIRI alone,cetuximabβplus FOLFIRI therapy led to prolonged median PFS and OS while maintaining a manageable safety profle,offering a new treatment option for this patient population.
基金This study was supported by the Chinese Society of Clinical Oncology(CSCO)-Hengrui Oncology Research Fund(No.Y-HR2018-364)。
文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).
基金This study was supported by the National Key Basic Research Program of China(973 Program No.2015CB553902)
文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.
基金support from the National Natural Science Foundation of China(Nos.82003206 and 82173338)Natural Science Foundation of Hunan Province(Nos.2020SK2031,2020SK2030,2021RC4040,and 2020JJ3025).
文摘Background:Immune checkpoint inhibitors(ICIs)are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer(NSCLC)harboring no actionable mutations;however,data on their efficacy among patients presenting with intracranial lesions are limited.This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.Methods:Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable,asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1,2019 and September 30,2021.The patients were stratified into two groups according to the first-line treatment regimen received:ICI combined with chemotherapy(n=102)or chemotherapy(n=109).Systemic and intracranial objective response rates(ORRs)and progression-free survival(PFS)were analyzed.Adverse events were also compared between the groups.Results:Compared with the chemotherapy-based regimen,the ICI-containing regimen was associated with a significantly higher intracranial(44.1%[45/102]vs.28.4%[31/109],χ^(2)=5.620,P=0.013)and systemic(49.0%[50/102]vs.33.9%[37/109],χ^(2)=4.942,P=0.019)ORRs and longer intracranial(11.0 months vs.7.0 months,P<0.001)and systemic(9.0 months vs.5.0 months,P<0.001)PFS.Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS(hazard ratio[HR]=0.52,95%confidence interval[CI]:0.37-0.73,P<0.001)and systemic PFS(HR=0.48,95%CI:0.35-0.66,P<0.001).No unexpected serious adverse effects were observed.Conclusion:Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.Clinical trial registration:https://www.clinicaltrials.gov/,OMESIA,NCT05129202.
基金supported by Chinese National Natural Science Funding[grant number 82172710,2021]the Shanghai Public Health Outstanding Academic Leader Program(GWVI-11.2-XD22,grant to Y.S.Z.)+4 种基金the Shanghai Oriental Talents Program(grant to Y.S.Z.)the Shanghai Municipal Health Commission Health Industry Clinical Research Project(202240277,grant to Z.W.20224Y0077,grant to B.D.Q.)the Innovation Clinical Research Project of Shanghai Changzheng Hospital[grant number 2020YLCYJ-Z03,2020grant number 2023YJBF-FH05,2023].
文摘This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APICAL-CRC ClinicalTrials.gov number,NCT04271813).Between June 2020 and September 2023,a total of 30 patients were eventually enrolled and received the study regimen.Among these 30 patients,50%had an Eastern Cooperative Oncology Group(ECOG)score of 0–1,and the other 50%had a score of 2.The objective response rates(ORRs)were 48.3%(95%CI 29.4–67.5)in the efficacy-evaluable cohort and 46.7%(95%CI 28.3–65.7)in the intent-to-treat(ITT)cohort.Twelve patients had stable disease,and the disease control rates(DCRs)were 89.7%(95%CI 72.6–97.8)and 86.7%(95%CI 69.3–96.2)in the efficacy-evaluable and ITT cohorts,respectively.The median progressionfree survival(mPFS)was 8.6 months(95%CI 4.8–11.0),and the median overall survival(mOS)reached 22.9 months(95%CI 13.5–36.3).Treatment-related adverse events(TRAEs)of any grade were reported in 23 patients(76.7%),and grade 3 TRAEs occurred in 4 patients(13.3%).Multivariate Cox regression analysis revealed that the presence of liver metastases was an independent prognostic factor for poor PFS(HR=5.66,95%CI 1.58–20.2)and OS(HR=7.85,95%CI 1.38–44.8),whereas FLT mutation was independently associated with poor OS(HR=12.5,95%CI 1.54–101).This trial demonstrated that sintilimab plus anlotinib exhibited promising antitumor efficacy along with a manageable safety profile among treatment-naïve mCRC patients.
基金supported by a key project(2018C03009)funded by the Zhejiang Provincial Department of Sciences and Technologies to X.H.and M.C.
文摘The objective response rate of conventional transarterial chemoembolization(TACE)for locoregional control of hepatocellular carcinoma(HCC)is approximately 50%.We previously developed bicarbonate-integrated TACE,termed TILA-TACE,which demonstrated 100%effectiveness for locoregional control of unresectable HCC.This study aimed to validate its efficacy,selectivity,and safety in real-world clinical practice(ChiCTR-ONC-17013416).A total of 413 patients were enrolled,including 40(9.7%)with early-stage HCC,29(7.0%)with intermediate-stage HCC,and 344(83.3%)with advanced-stage HCC.Primary tumors and macrovascular invasion/extrahepatic metastases were treated with TILA-TACE and radiation therapy,respectively.The side effects of TILA-TACE were recorded.The objective response rate of HCC tumors to TILA-TACE was 99.01%,including a complete response in 72.77%of patients.The objective response rate of tumor thrombus to radiation therapy was 96.88%.During a median follow-up of 38 months,there were 1 and 4 deaths among early-and intermediate-stage patients,respectively.The median survival of advanced-stage patients was 27 months.We found that intrahepatic metastases accounted for 70.4%(107/152)of cancer-related deaths after effective control of primary tumors and vascular invasion.The main adverse events associated with TILA-TACE were transient liver enzyme or bilirubin abnormalities(86.44%and 56.66%,respectively),which was consistent with the known sideeffect profile of TACE.In conclusion,TILA-TACE is a novel and highly effective treatment for the local control of HCC with a tolerable safety profile.When combined with radiation therapy for macrovascular invasion,it offers significant survival benefits for patients with advanced HCC.
