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
The objective stress rate is a rather important problem in mechanics of finite deformation. In this paper, the objective stress rate in co-moving coordinate is derived by applying nonlinear geometric field theory of d...The objective stress rate is a rather important problem in mechanics of finite deformation. In this paper, the objective stress rate in co-moving coordinate is derived by applying nonlinear geometric field theory of deformation. Problems, such ax targe extension coupled with rotation, and large shear deformation, are exemplified by using the new formula. Comparing with Jaumann 's stress rate and other formulae presented in current literature, the new result appears to be the reasonable one in co-moving coordinate system.展开更多
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 endochronic equations proposed by Valanis (1980) were extended to a finite deformation range. Jaumanns rate, Fus rate and Wus rate were incorporated into the endochronic equations to analyze simple shear finite de...The endochronic equations proposed by Valanis (1980) were extended to a finite deformation range. Jaumanns rate, Fus rate and Wus rate were incorporated into the endochronic equations to analyze simple shear finite deformation. Incremental equations and numerical solutions are deduced for three endochronic objective models. The results show that an oscillatory shear stress response to a monotonically increasing shear strain occurs when the Jaumanns rate objective model is employed for endochronic materials. The oscillatory response is dependent on the adopted objective rate. Compared with the Jaumanns rate, the Fus rate and the Wus rate satisfy the restrictions to elastic-plastic constitutive relations and are in agreement with the experimental results.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 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
Jaumann rate, generalized Jaumann rate,Fu rate and Wu rate were incorporated into endochronic equations for finite plastic deformation to analyze simple shear finite deformation. The results show that an oscillatory s...Jaumann rate, generalized Jaumann rate,Fu rate and Wu rate were incorporated into endochronic equations for finite plastic deformation to analyze simple shear finite deformation. The results show that an oscillatory shear stress and normal stress response to a monotonically increasing shear strain occurs when Jaumann rate objective model is adopted for hypoelastic or endochronic materials. The oscillatory response is dependent on objective rate adopted,independent on elastoplastic models. Normal stress is unequal to zero during simple shear finite deformation.展开更多
A dynamic learning rate Gaussian mixture model（GMM）algorithm is proposed to deal with the problem of slow adaption of GMM in the case of moving object detection in the outdoor surveillance,especially in the presence...A dynamic learning rate Gaussian mixture model（GMM）algorithm is proposed to deal with the problem of slow adaption of GMM in the case of moving object detection in the outdoor surveillance,especially in the presence of sudden illumination changes.The GMM is mostly used for detecting objects in complex scenes for intelligent monitoring systems.To solve this problem,a mixture Gaussian model has been built for each pixel in the video frame,and according to the scene change from the frame difference,the learning rate of GMM can be dynamically adjusted.The experiments show that the proposed method gives good results with an adaptive GMM learning rate when we compare it with GMM method with a fixed learning rate.The method was tested on a certain dataset,and tests in the case of sudden natural light changes show that our method has a better accuracy and lower false alarm rate.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
The calibration of conventional,hybrid and electric drivetrains is an important process during the development phase of any vehicle.Therefore,to optimize the comfort and dynamic behavior(known as driveability),many te...The calibration of conventional,hybrid and electric drivetrains is an important process during the development phase of any vehicle.Therefore,to optimize the comfort and dynamic behavior(known as driveability),many test drives are performed by experienced drivers during different driving maneuvers,e.g.,launch,re-launch or gear shift.However,the process can be kept more consistent and independent of human-based deviations by using objective ratings.This study first introduces an objective rating system developed for the launch behavior of conventional vehicles with automatic transmission,dual-clutch transmission,and alternative drivetrains.Then,the launch behavior,namely comfort and dynamic quality,is compared between two conventional vehicles,a plug-in hybrid electric vehicle and a battery electric vehicle.Results show the benefits of pure electric drivetrains due to the lack of launch and shifting elements,as well as the usage of a highly dynamic electric motor.While the plug-in hybrid achieves a 10%higher overall rating compared to the baseline conventional vehicle,the pure electric vehicle even achieves a 21%higher overall rating.The results also highlight the optimization potential of battery electric vehicles regarding their comfort and dynamic characteristics.The transitions and the gradient of the acceleration build-up have a major influence on the launch quality.展开更多
Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-...Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.展开更多
CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase ...CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.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
Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evalu...Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC.Participants received TACE followed by atezolizumab and bevacizumab until disease progression,unacceptable toxicity,or death.The primary endpoint was objective response rate(ORR)assessed per Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Secondary endpoints included progression-free survival(PFS),overall survival(OS),ORR by modified RECIST(mRECIST),disease control rate(DCR),time to response(TTR),duration of response(DOR),and adverse events(AEs).Between August 21,2021 and April 10,2023,45 patients were enrolled.As of the data cutoff on September 30,2024,the median follow-up was 26.7 months.The ORR was 47%per RECIST v1.1 and 67%per mRECIST.Median PFS was 17.9 months,and median OS was 33.0 months.The DCR was 87%(RECIST v1.1)and 91%(mRECIST).Median TTR was 11.9 weeks(RECIST v1.1)and 4.9 weeks(mRECIST),with median DOR of 36.6 weeks(RECIST v1.1)and 44.4 weeks(mRECIST).Of the 45 patients,44 experienced AEs of any grade,with 20 reporting grade 3-4 AEs;no grade 5 AEs were observed.TACE combined with atezolizumab and bevacizumab appears safe and feasible for intermediate-stage HCC,supporting further investigation in larger studies.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
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
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The objective stress rate is a rather important problem in mechanics of finite deformation. In this paper, the objective stress rate in co-moving coordinate is derived by applying nonlinear geometric field theory of deformation. Problems, such ax targe extension coupled with rotation, and large shear deformation, are exemplified by using the new formula. Comparing with Jaumann 's stress rate and other formulae presented in current literature, the new result appears to be the reasonable one in co-moving coordinate system.
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 endochronic equations proposed by Valanis (1980) were extended to a finite deformation range. Jaumanns rate, Fus rate and Wus rate were incorporated into the endochronic equations to analyze simple shear finite deformation. Incremental equations and numerical solutions are deduced for three endochronic objective models. The results show that an oscillatory shear stress response to a monotonically increasing shear strain occurs when the Jaumanns rate objective model is employed for endochronic materials. The oscillatory response is dependent on the adopted objective rate. Compared with the Jaumanns rate, the Fus rate and the Wus rate satisfy the restrictions to elastic-plastic constitutive relations and are in agreement with the experimental results.
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 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Jaumann rate, generalized Jaumann rate,Fu rate and Wu rate were incorporated into endochronic equations for finite plastic deformation to analyze simple shear finite deformation. The results show that an oscillatory shear stress and normal stress response to a monotonically increasing shear strain occurs when Jaumann rate objective model is adopted for hypoelastic or endochronic materials. The oscillatory response is dependent on objective rate adopted,independent on elastoplastic models. Normal stress is unequal to zero during simple shear finite deformation.
文摘A dynamic learning rate Gaussian mixture model（GMM）algorithm is proposed to deal with the problem of slow adaption of GMM in the case of moving object detection in the outdoor surveillance,especially in the presence of sudden illumination changes.The GMM is mostly used for detecting objects in complex scenes for intelligent monitoring systems.To solve this problem,a mixture Gaussian model has been built for each pixel in the video frame,and according to the scene change from the frame difference,the learning rate of GMM can be dynamically adjusted.The experiments show that the proposed method gives good results with an adaptive GMM learning rate when we compare it with GMM method with a fixed learning rate.The method was tested on a certain dataset,and tests in the case of sudden natural light changes show that our method has a better accuracy and lower false alarm rate.
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The calibration of conventional,hybrid and electric drivetrains is an important process during the development phase of any vehicle.Therefore,to optimize the comfort and dynamic behavior(known as driveability),many test drives are performed by experienced drivers during different driving maneuvers,e.g.,launch,re-launch or gear shift.However,the process can be kept more consistent and independent of human-based deviations by using objective ratings.This study first introduces an objective rating system developed for the launch behavior of conventional vehicles with automatic transmission,dual-clutch transmission,and alternative drivetrains.Then,the launch behavior,namely comfort and dynamic quality,is compared between two conventional vehicles,a plug-in hybrid electric vehicle and a battery electric vehicle.Results show the benefits of pure electric drivetrains due to the lack of launch and shifting elements,as well as the usage of a highly dynamic electric motor.While the plug-in hybrid achieves a 10%higher overall rating compared to the baseline conventional vehicle,the pure electric vehicle even achieves a 21%higher overall rating.The results also highlight the optimization potential of battery electric vehicles regarding their comfort and dynamic characteristics.The transitions and the gradient of the acceleration build-up have a major influence on the launch quality.
文摘Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.
基金sponsored by the Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.
文摘CDK2 is a principal mediator of CDK4/6 resistance.Concurrent CDK2/4/6 blockade may be effective in treating HR-positive,HER2-negative advanced breast cancer(ABC).This randomized,double-blind,parallel-controlled,phase 3 trial(ClinicalTrials.gov,NCT05375461)assessed the efficacy of culmerciclib,a CDK2/4/6 inhibitor,plus fulvestrant in ABC.Patients with HR-positive,HER2-negative,locally recurrent or metastatic breast cancer were randomized(2:1)to receive culmerciclib plus fulvestrant or matching placebo plus fulvestrant.Between March 18,2022 and March 3,2023,293 pretreated patients(median age 53.0 years;pre-or perimenopausal 42.3%;bone metastasis 65.2%)were randomized to assigned treatments.At this prespecified interim analysis,culmerciclib plus fulvestrant extended the median investigator-assessed progression-free survival(PFS)significantly,the primary endpoint,as compared with placebo plus fulvestrant(16.6 months,95%CI 13.8 to not evaluable versus 7.5 months,95%CI 5.3 to 11.0;hazard ratio 0.36,95%CI 0.26–0.51;stratified log rank test P<0.001).Consistent effects were observed across diverse subgroups of patients.At a median follow-up duration of 13.8 months,overall survival was immature.The investigators-assessed objective response rate was 40.2%(95%CI,33.3–47.5)for culmerciclib compared to 12.1%(95%CI 6.4–20.2)for placebo(stratified Mantel-Haenszelχ2 test P<0.001).Diarrhea(87.1%)and neutropenia(80.4%)were the most common toxicities with culmerciclib plus fulvestrant.In conclusion,this randomized clinical trial met its primary outcome.Culmerciclib plus fulvestrant is well tolerated and leads to a significant gain in PFS of pretreated HR-positive HER2-negative ABC patients.
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supported by the National Key Research and Development Program of China(2022YFC2503700,2022YFC2503705)National Natural Science Foundation of China(82473487)+2 种基金Shanghai Municipal Health Commission(2023ZZ02005)Shanghai Oriental Talents Program Youth Project(QNWS2024076)Zhejiang Provincial Key Laboratory of Medical Electronic and Digital Health(MEDH202207).
文摘Transarterial chemoembolization(TACE)is the standard treatment for intermediate-stage hepatocellular carcinoma(HCC),yet its efficacy as a standalone therapy remains suboptimal.This phase 2 trial(ChiCTR2100049829)evaluated the feasibility and safety of TACE combined with atezolizumab and bevacizumab in patients with intermediate-stage HCC.Participants received TACE followed by atezolizumab and bevacizumab until disease progression,unacceptable toxicity,or death.The primary endpoint was objective response rate(ORR)assessed per Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Secondary endpoints included progression-free survival(PFS),overall survival(OS),ORR by modified RECIST(mRECIST),disease control rate(DCR),time to response(TTR),duration of response(DOR),and adverse events(AEs).Between August 21,2021 and April 10,2023,45 patients were enrolled.As of the data cutoff on September 30,2024,the median follow-up was 26.7 months.The ORR was 47%per RECIST v1.1 and 67%per mRECIST.Median PFS was 17.9 months,and median OS was 33.0 months.The DCR was 87%(RECIST v1.1)and 91%(mRECIST).Median TTR was 11.9 weeks(RECIST v1.1)and 4.9 weeks(mRECIST),with median DOR of 36.6 weeks(RECIST v1.1)and 44.4 weeks(mRECIST).Of the 45 patients,44 experienced AEs of any grade,with 20 reporting grade 3-4 AEs;no grade 5 AEs were observed.TACE combined with atezolizumab and bevacizumab appears safe and feasible for intermediate-stage HCC,supporting further investigation in larger studies.
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.
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).
