Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic ...Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.展开更多
Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemo...Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.展开更多
Objective： Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients＇ quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the e...Objective： Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients＇ quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy（PIPN） in Chinese breast cancer patients.Methods：A total of 102 patients with a median age of 50（range,25–60）years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine（for the first 4 weeks）and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane（FACT-Tax）Scales,which contained questions scored from 0 to 4（0,not at all;4,very much;total score range,0–44）.Results：Duloxetine was more effective in decreasing PIPN（odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002）.Between duloxetine group and control group,the median（25th–75th percentiles）decreasing difference in the FACT-Tax pain score was 4（2–6）vs.1（0–4）（P=0.005）.Conclusions：Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required.展开更多
Minimax optimization problems are an important class of optimization problems arising from modern machine learning and traditional research areas.While there have been many numerical algorithms for solving smooth conv...Minimax optimization problems are an important class of optimization problems arising from modern machine learning and traditional research areas.While there have been many numerical algorithms for solving smooth convex-concave minimax problems,numerical algorithms for nonsmooth convex-concave minimax problems are rare.This paper aims to develop an efficient numerical algorithm for a structured nonsmooth convex-concave minimax problem.A semi-proximal point method(SPP)is proposed,in which a quadratic convex-concave function is adopted for approximating the smooth part of the objective function and semi-proximal terms are added in each subproblem.This construction enables the subproblems at each iteration are solvable and even easily solved when the semiproximal terms are cleverly chosen.We prove the global convergence of our algorithm under mild assumptions,without requiring strong convexity-concavity condition.Under the locally metrical subregularity of the solution mapping,we prove that our algorithm has the linear rate of convergence.Preliminary numerical results are reported to verify the efficiency of our algorithm.展开更多
Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemest...Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).展开更多
Over the past 2 decades,there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer.Trastuzumab,pertuzumab,lapatinib,an...Over the past 2 decades,there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer.Trastuzumab,pertuzumab,lapatinib,and ado-trastuzumab emtansine(T-DM1)are commonly recommended anti-HER2 target agents by the U.S.Food and Drug Administration.This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices.In this article,we present the data on anti-HER2 clinical research of neoadjuvant,adjuvant,and metastatic studies from the past 2 decades.We also highlight some of the promising strategies that should be critically considered.Lastly,this review lists some of the ongoing clinical trials,findings of which may soon be available.展开更多
Circulating tumor DNA(ctDNA)is a potential biomarker of prognosis and therapeutic response.We conducted this study to explore the role of the molecular tumor burden index(mTBI)in ctDNA as a therapeutic response and pr...Circulating tumor DNA(ctDNA)is a potential biomarker of prognosis and therapeutic response.We conducted this study to explore the role of the molecular tumor burden index(mTBI)in ctDNA as a therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study.We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study(NCT01917279).Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples.The pretreatment mTBI value was correlated with tumor burden(P=0.025).Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI,and the median overall survival was 40.9 months and 68.4 months,respectively(P=0.011).Patients with mTBI decrease to less than 0.02%at the first tumor evaluation had longer progression-free survival and overall survival(P<0.001 and P=0.007,respectively).The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans(88.5%and 87.5%,respectively).The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort(P<0.001 and P=0.036,respectively),as well as in the cohort in which computed tomography scans were defined as representing stable disease(P=0.027 and P=0.015,respectively).The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.展开更多
In this paper,we study a stochastic Newton method for nonlinear equations,whose exact function information is difficult to obtain while only stochastic approximations are available.At each iteration of the proposed al...In this paper,we study a stochastic Newton method for nonlinear equations,whose exact function information is difficult to obtain while only stochastic approximations are available.At each iteration of the proposed algorithm,an inexact Newton step is first computed based on stochastic zeroth-and first-order oracles.To encourage the possible reduction of the optimality error,we then take the unit step size if it is acceptable by an inexact Armijo line search condition.Otherwise,a small step size will be taken to help induce desired good properties.Then we investigate convergence properties of the proposed algorithm and obtain the almost sure global convergence under certain conditions.We also explore the computational complexities to find an approximate solution in terms of calls to stochastic zeroth-and first-order oracles,when the proposed algorithm returns a randomly chosen output.Furthermore,we analyze the local convergence properties of the algorithm and establish the local convergence rate in high probability.At last we present preliminary numerical tests and the results demonstrate the promising performances of the proposed algorithm.展开更多
To the Editor:Oncology precision medicine aims to identify patientsmostlikely torespondeffectivelytotherapies.Efforts to establish a survival prediction model using a single platform have not yet met the precision med...To the Editor:Oncology precision medicine aims to identify patientsmostlikely torespondeffectivelytotherapies.Efforts to establish a survival prediction model using a single platform have not yet met the precision medicine goals.展开更多
Cancer informatics has significantly progressed in the big data era.We summarize the application of informatics approaches to the cancer domain from both the informatics perspective(e.g.,data management and data scien...Cancer informatics has significantly progressed in the big data era.We summarize the application of informatics approaches to the cancer domain from both the informatics perspective(e.g.,data management and data science)and the clinical perspective(e.g.,cancer screening,risk assessment,diagnosis,treatment,and prognosis).We discuss various informatics methods and tools that are widely applied in cancer research and practices,such as cancer databases,data standards,terminologies,high‐throughput omics data mining,machine‐learning algorithms,artificial intelligence imaging,and intelligent radiation.We also address the informatics challenges within the cancer field that pursue better treatment decisions and patient outcomes,and focus on how informatics can provide opportunities for cancer research and practices.Finally,we conclude that the interdisciplinary nature of cancer informatics and collaborations are major drivers for future research and applications in clinical practices.It is hoped that this review is instrumental for cancer researchers and clinicians with its informatics‐specific insights.展开更多
Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteri...Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics.To address these issues,single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC.This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes(IIEGs)through single-cell technology and machine learning,providing insights into immune infiltration,enhancing predictive accuracy,and facilitating the development of more effective treatment strategies.Materials and methods:The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC.Various tools,including the Human Protein Atlas,cBioPortal,single-cell analysis,machine learning,and Kaplan-Meier plot,were used to analyze IIEGs.Functional enrichment analysis was conducted to explore potential mechanisms.In addition,the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis,CIBERSORT,xCELL,and tumor immunophenotype algorithms.The expression of glycosylphosphatidylinositol anchor attachment 1(GPAA1)was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemical staining.Results:Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC.Using random forest,least absolute shrinkage and selection operator regression analysis,and support vector machine,a risk score model consisting of six IIEGs(carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD),phosphatidylinositol glycan anchor biosynthesis class U(PIGU),endoplasmic reticulum membrane protein complex subunit 3(EMC3),centrosomal protein 55(CEP55),autophagyrelated 10(ATG10),and GPAA1)developed,which was validated using 10 pairs of HCC and adjacent non-cancerous samples.Based on the calculated median risk score,HCC samples were categorized into high-and low-risk groups.The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group.Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis.Furthermore,immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.Conclusions:A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC.The utilization of the IIEG risk score as a novel prognostic index,together with its significance as a valuable biomarker for immunotherapy in HCC,provides benefit for patients with HCC in determining therapeutic strategies for clinical application.展开更多
In this paper,we analyze the convergence properties of a stochastic augmented Lagrangian method for solving stochastic convex programming problems with inequality constraints.Approximation models for stochastic convex...In this paper,we analyze the convergence properties of a stochastic augmented Lagrangian method for solving stochastic convex programming problems with inequality constraints.Approximation models for stochastic convex programming problems are constructed from stochastic observations of real objective and constraint functions.Based on relations between solutions of the primal problem and solutions of the dual problem,it is proved that the convergence of the algorithm from the perspective of the dual problem.Without assumptions on how these random models are generated,when estimates are merely sufficiently accurate to the real objective and constraint functions with high enough,but fixed,probability,the method converges globally to the optimal solution almost surely.In addition,sufficiently accurate random models are given under different noise assumptions.We also report numerical results that show the good performance of the algorithm for different convex programming problems with several random models.展开更多
基金supported by grants from the CAMS Innovation Fund for Medical Sciences[CIFMS](Grant Nos.2021-I2M-1-014 and 2022-I2M-2-002).
文摘Objective:CDK4/6 inhibitors(CDK4/6is)in combination with endocrine therapy have secured a central role in the treatment of hormone receptor(HR)-positive advanced breast cancer(ABC)and have transformed the therapeutic landscape.Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects.Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2(HER2)–ABC.Methods:This retrospective study enrolled 82 patients with HR+/HER2–ABC who were treated with cross-line CDK4/6is(abemaciclib,palbociclib,ribociclib,and dalpiciclib)after progression with another CDK4/6i.The primary endpoint was progression-free survival(PFS)according to version 1.1 of the Response Evaluation Criteria in Solid Tumors.Secondary endpoints included toxicity,objective response rate,disease control rate,and overall survival.Adverse events(AEs)were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events,as promulgated by the U.S.Department of Health and Human Services.Results:Eighty-two HR+/HER2–ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled.The median age of the patients was 60 years.The median PFS of all patients was 7.6 months(95%CI,5.9-9.2).Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS.Notably,patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months.The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i,then to a subsequent CDK4/6i merits further investigation.Hematologic toxicity was the most common grade≥3 AEs.No instances of fatal safety events were observed.Conclusions:Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2–ABC,which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.
基金This work was supported by National Key Research and Development Program of China(No.2O18YFC13121O1)Chinese Academy of Medical Science Initiative for Innovative Medicine(No.CAMS-2016-I2M-1-010).
文摘Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.
文摘Objective： Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients＇ quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy（PIPN） in Chinese breast cancer patients.Methods：A total of 102 patients with a median age of 50（range,25–60）years,treated in the Department of Medical Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,between November 2014 and January 2017 were finally enrolled.Stratified by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity drugs.During the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events.The treatment consisted of receiving 30 mg duloxetine（for the first 4 weeks）and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover period.The improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane（FACT-Tax）Scales,which contained questions scored from 0 to 4（0,not at all;4,very much;total score range,0–44）.Results：Duloxetine was more effective in decreasing PIPN（odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002）.Between duloxetine group and control group,the median（25th–75th percentiles）decreasing difference in the FACT-Tax pain score was 4（2–6）vs.1（0–4）（P=0.005）.Conclusions：Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with PIPN.Non-neuropathy adverse events were mild and similar in both groups.The major toxicities of duloxetine included nausea,constipation,somnolence,dizziness and distention of the eyes.Further examination of the benefits of duloxetine in the prevention of PIPN is required.
基金supported by the Natural Science Foundation of China(Grant Nos.11991021,11991020,12021001,11971372,11971089,11731013)by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA27000000)by the National Key R&D Program of China(Grant Nos.2021YFA1000300,2021YFA1000301).
文摘Minimax optimization problems are an important class of optimization problems arising from modern machine learning and traditional research areas.While there have been many numerical algorithms for solving smooth convex-concave minimax problems,numerical algorithms for nonsmooth convex-concave minimax problems are rare.This paper aims to develop an efficient numerical algorithm for a structured nonsmooth convex-concave minimax problem.A semi-proximal point method(SPP)is proposed,in which a quadratic convex-concave function is adopted for approximating the smooth part of the objective function and semi-proximal terms are added in each subproblem.This construction enables the subproblems at each iteration are solvable and even easily solved when the semiproximal terms are cleverly chosen.We prove the global convergence of our algorithm under mild assumptions,without requiring strong convexity-concavity condition.Under the locally metrical subregularity of the solution mapping,we prove that our algorithm has the linear rate of convergence.Preliminary numerical results are reported to verify the efficiency of our algorithm.
基金sponsored by EOC Pharmaceutical CO,and CAMS Innovation Fund for Medical Sciences(CIFMS,2021I2M-1-014,China)Taizhou EOC Pharma Co.,Ltd.for supporting,developing and sponsoring this trial。
文摘Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging outcomes.This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine therapy.Patients were randomized(2:1)to oral exemestane 25 mg/day plus entinostat(n=235)or placebo(n=119)5 mg/week in 28-day cycles.The primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52(range,28—75)years and 222(62.7%)patients were postmenopausal.CDK4/6 inhibitors and fulvestrant were previously used in 23(6.5%)and 92(26.0%)patients,respectively.The baseline characteristics were comparable between the entinostat and placebo groups.The median PFS was 6.32(95%CI,5.30—9.11)and 3.72(95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),respectively.Grade≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 23(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[20(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(ClinicalTrials.gov#NCT03538171).
文摘Over the past 2 decades,there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer.Trastuzumab,pertuzumab,lapatinib,and ado-trastuzumab emtansine(T-DM1)are commonly recommended anti-HER2 target agents by the U.S.Food and Drug Administration.This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices.In this article,we present the data on anti-HER2 clinical research of neoadjuvant,adjuvant,and metastatic studies from the past 2 decades.We also highlight some of the promising strategies that should be critically considered.Lastly,this review lists some of the ongoing clinical trials,findings of which may soon be available.
基金This work was supported by‘National Natural Science Foundation of China’(Grant Number:81874122)‘CAMS Initiative for Innovative Medicine’(Grant Number:2017-I2M-3-004)‘Major Project of the Beijing Municipal Science and Technology Commission’(Grant Number:D161100000816004).
文摘Circulating tumor DNA(ctDNA)is a potential biomarker of prognosis and therapeutic response.We conducted this study to explore the role of the molecular tumor burden index(mTBI)in ctDNA as a therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study.We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study(NCT01917279).Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples.The pretreatment mTBI value was correlated with tumor burden(P=0.025).Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI,and the median overall survival was 40.9 months and 68.4 months,respectively(P=0.011).Patients with mTBI decrease to less than 0.02%at the first tumor evaluation had longer progression-free survival and overall survival(P<0.001 and P=0.007,respectively).The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans(88.5%and 87.5%,respectively).The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort(P<0.001 and P=0.036,respectively),as well as in the cohort in which computed tomography scans were defined as representing stable disease(P=0.027 and P=0.015,respectively).The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.
基金supported by the National Natural Science Foundation of China (Nos.11731013,11871453 and 11971089)Young Elite Scientists Sponsorship Program by CAST (No.2018QNRC001)+1 种基金Youth Innovation Promotion Association,CASFundamental Research Funds for the Central Universities,UCAS.
文摘In this paper,we study a stochastic Newton method for nonlinear equations,whose exact function information is difficult to obtain while only stochastic approximations are available.At each iteration of the proposed algorithm,an inexact Newton step is first computed based on stochastic zeroth-and first-order oracles.To encourage the possible reduction of the optimality error,we then take the unit step size if it is acceptable by an inexact Armijo line search condition.Otherwise,a small step size will be taken to help induce desired good properties.Then we investigate convergence properties of the proposed algorithm and obtain the almost sure global convergence under certain conditions.We also explore the computational complexities to find an approximate solution in terms of calls to stochastic zeroth-and first-order oracles,when the proposed algorithm returns a randomly chosen output.Furthermore,we analyze the local convergence properties of the algorithm and establish the local convergence rate in high probability.At last we present preliminary numerical tests and the results demonstrate the promising performances of the proposed algorithm.
基金National Key Research and Development Program of China(2021YFF1201300 and 2021YFF1201003)the National Natural Science Foundation of China(Nos.81971662 and 92059103)+1 种基金the Natural Science Foundation of Beijing City(7202105)the Key Project of Beijing Hope Marathon Special Fund from the China Cancer Foundation(LC2018A20)
文摘To the Editor:Oncology precision medicine aims to identify patientsmostlikely torespondeffectivelytotherapies.Efforts to establish a survival prediction model using a single platform have not yet met the precision medicine goals.
基金National Key Research&Development Program of China。
文摘Cancer informatics has significantly progressed in the big data era.We summarize the application of informatics approaches to the cancer domain from both the informatics perspective(e.g.,data management and data science)and the clinical perspective(e.g.,cancer screening,risk assessment,diagnosis,treatment,and prognosis).We discuss various informatics methods and tools that are widely applied in cancer research and practices,such as cancer databases,data standards,terminologies,high‐throughput omics data mining,machine‐learning algorithms,artificial intelligence imaging,and intelligent radiation.We also address the informatics challenges within the cancer field that pursue better treatment decisions and patient outcomes,and focus on how informatics can provide opportunities for cancer research and practices.Finally,we conclude that the interdisciplinary nature of cancer informatics and collaborations are major drivers for future research and applications in clinical practices.It is hoped that this review is instrumental for cancer researchers and clinicians with its informatics‐specific insights.
基金the Natural Science Foundation of Guangdong Province(No.2017A030310252,No.2022A1515012650)the Science and Technology Program of Guangzhou(No.2024A03J0919).
文摘Background and aims:Hepatocellular carcinoma(HCC)is a tumor of high heterogeneity and complexity,which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics.To address these issues,single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC.This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes(IIEGs)through single-cell technology and machine learning,providing insights into immune infiltration,enhancing predictive accuracy,and facilitating the development of more effective treatment strategies.Materials and methods:The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC.Various tools,including the Human Protein Atlas,cBioPortal,single-cell analysis,machine learning,and Kaplan-Meier plot,were used to analyze IIEGs.Functional enrichment analysis was conducted to explore potential mechanisms.In addition,the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis,CIBERSORT,xCELL,and tumor immunophenotype algorithms.The expression of glycosylphosphatidylinositol anchor attachment 1(GPAA1)was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction,Western blotting,and immunohistochemical staining.Results:Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC.Using random forest,least absolute shrinkage and selection operator regression analysis,and support vector machine,a risk score model consisting of six IIEGs(carbamoyl-phosphate synthetase 2,aspartate transcarbamylase,and dihydroorotase(CAD),phosphatidylinositol glycan anchor biosynthesis class U(PIGU),endoplasmic reticulum membrane protein complex subunit 3(EMC3),centrosomal protein 55(CEP55),autophagyrelated 10(ATG10),and GPAA1)developed,which was validated using 10 pairs of HCC and adjacent non-cancerous samples.Based on the calculated median risk score,HCC samples were categorized into high-and low-risk groups.The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group.Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis.Furthermore,immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.Conclusions:A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC.The utilization of the IIEG risk score as a novel prognostic index,together with its significance as a valuable biomarker for immunotherapy in HCC,provides benefit for patients with HCC in determining therapeutic strategies for clinical application.
基金supported by the National Key R&D Program of China(Project No.2022YFA1004000)by the Natural Science Foundation of China(Project No.12371298).
文摘In this paper,we analyze the convergence properties of a stochastic augmented Lagrangian method for solving stochastic convex programming problems with inequality constraints.Approximation models for stochastic convex programming problems are constructed from stochastic observations of real objective and constraint functions.Based on relations between solutions of the primal problem and solutions of the dual problem,it is proved that the convergence of the algorithm from the perspective of the dual problem.Without assumptions on how these random models are generated,when estimates are merely sufficiently accurate to the real objective and constraint functions with high enough,but fixed,probability,the method converges globally to the optimal solution almost surely.In addition,sufficiently accurate random models are given under different noise assumptions.We also report numerical results that show the good performance of the algorithm for different convex programming problems with several random models.
