BACKGROUND Hepatocellular carcinoma(HCC)is a major global contributor to cancer-related mortality,with advanced stages presenting substantial therapeutic challenges.Although targeted immunotherapy shows potential,many...BACKGROUND Hepatocellular carcinoma(HCC)is a major global contributor to cancer-related mortality,with advanced stages presenting substantial therapeutic challenges.Although targeted immunotherapy shows potential,many patients exhibit poor responses,underscoring the need for predictive tools to optimize treatment strategies.Emerging data indicate that ultrasound features(e.g.,tumor stiffness)and serum biomarkers may serve as predictors of treatment outcomes.However,an integrated model for these predictors remains unavailable.This paper introduces a machine learning-based approach that combines ultrasound and serological data to forecast immunotherapy efficacy in patients with advanced HCC.AIM To develop a non-invasive predictive model for targeted immunotherapy in advanced HCC,incorporating both internal and external validation.METHODS Patients with advanced HCC who received targeted immunotherapy at two medical centers were enrolled and divided into internal training,internal validation,and external validation cohorts.Comprehensive clinical data were gathered.Initially,13 machine learning algorithms were tested using the internal training cohort.The algorithm yielding the highest area under the curve(AUC)in the internal validation cohort was selected to construct a predictive model,termed the Target Immunotherapy Predictive Model(TIPM).TIPM performance was then compared with that of traditional tumor staging systems(tumor-node-metastasis,Barcelona Clinic Liver Cancer,China Liver Cancer,Hong Kong Liver Cancer,and C-reactive protein and alpha-fetoprotein in immunotherapy).RESULTS A total of 306 patients participated in the study,with 143 in the internal training cohort,62 in the internal validation cohort,and 101 in the external validation cohort.In the internal validation cohort,the random forest model achieved the highest AUC(0.975,95%confidence interval:0.924-0.998).The key predictors for TIPM were tumor size,platelet count,tumor stiffness change,and white blood cell count.During external validation,TIPM outperformed conventional models,reaching an AUC of 0.899(95%confidence interval:0.840-0.957).Calibration curves demonstrated strong concordance with observed outcomes,while decision curve analysis confirmed TIPM’s enhanced clinical value.Additional metrics,such as the net reclassification index and integrated discrimination improvement,further supported TIPM’s superior predictive accuracy.CONCLUSION TIPM provides a robust tool for predicting targeted immunotherapy efficacy in advanced HCC,facilitating personalized treatment planning.展开更多
Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosi...Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.展开更多
BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immu...BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.展开更多
Primary liver cancer is the sixth most prevalent malignancy worldwide and the third leading cause of cancer-related death.According to the latest data from the National Cancer Center of China,its mortality rate has ri...Primary liver cancer is the sixth most prevalent malignancy worldwide and the third leading cause of cancer-related death.According to the latest data from the National Cancer Center of China,its mortality rate has risen,making it the country’s second-deadliest tumor.Hepatocellular carcinoma(HCC),the predo-minant histological subtype,remains a substantial therapeutic challenge.Hepa-tectomy is the treatment of choice for HCC;however,because of its insidious onset and aggressive progression,the global 5-year survival rate is only 14.1%,and up to 70%of patients experience recurrence within five years after surgery.Consequently,reducing postoperative recurrence and prolonging survival have become critical research priorities.Currently,no consensus or guidelines exist regarding the clinical efficacy or potential synergistic effects of diagnostic and therapeutic strategies to prevent postoperative recurrence.In recent years,interest has grown in systemic therapies and combined local modalities-particularly targeted agents and immune checkpoint inhibitors,as adjuvant treatments.This review synthesizes recent advances in targeted and immunotherapeutic adjuvant therapies for postoperative HCC to inform clinical practice and improve patient outcomes.展开更多
This manuscript provides a comprehensive review and highlights of the 2015 San Antonio Breast Cancer Symposium by the leading breast cancer specialists and investigators in the field.
基金Supported by Natural Science Foundation of Fujian Province,No.2022J011285 and No.2023J011480Fuzhou Municipal Bureau of Science and Technology Program Fund,No.2021-S-109+1 种基金Provincial Subsidy Fund for Health and Wellness from Fujian Provincial Department of Finance,No.BPB-2022YXJFujian Provincial Health Technology Project,No.2020GGB032。
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major global contributor to cancer-related mortality,with advanced stages presenting substantial therapeutic challenges.Although targeted immunotherapy shows potential,many patients exhibit poor responses,underscoring the need for predictive tools to optimize treatment strategies.Emerging data indicate that ultrasound features(e.g.,tumor stiffness)and serum biomarkers may serve as predictors of treatment outcomes.However,an integrated model for these predictors remains unavailable.This paper introduces a machine learning-based approach that combines ultrasound and serological data to forecast immunotherapy efficacy in patients with advanced HCC.AIM To develop a non-invasive predictive model for targeted immunotherapy in advanced HCC,incorporating both internal and external validation.METHODS Patients with advanced HCC who received targeted immunotherapy at two medical centers were enrolled and divided into internal training,internal validation,and external validation cohorts.Comprehensive clinical data were gathered.Initially,13 machine learning algorithms were tested using the internal training cohort.The algorithm yielding the highest area under the curve(AUC)in the internal validation cohort was selected to construct a predictive model,termed the Target Immunotherapy Predictive Model(TIPM).TIPM performance was then compared with that of traditional tumor staging systems(tumor-node-metastasis,Barcelona Clinic Liver Cancer,China Liver Cancer,Hong Kong Liver Cancer,and C-reactive protein and alpha-fetoprotein in immunotherapy).RESULTS A total of 306 patients participated in the study,with 143 in the internal training cohort,62 in the internal validation cohort,and 101 in the external validation cohort.In the internal validation cohort,the random forest model achieved the highest AUC(0.975,95%confidence interval:0.924-0.998).The key predictors for TIPM were tumor size,platelet count,tumor stiffness change,and white blood cell count.During external validation,TIPM outperformed conventional models,reaching an AUC of 0.899(95%confidence interval:0.840-0.957).Calibration curves demonstrated strong concordance with observed outcomes,while decision curve analysis confirmed TIPM’s enhanced clinical value.Additional metrics,such as the net reclassification index and integrated discrimination improvement,further supported TIPM’s superior predictive accuracy.CONCLUSION TIPM provides a robust tool for predicting targeted immunotherapy efficacy in advanced HCC,facilitating personalized treatment planning.
文摘Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.
基金Supported by Natural Science Foundation of Henan Province,No.242300421286the research and practice project of higher education reform in Henan Province,No.2023SJGLX124Ythe research and practice project of higher education reform of Zhengzhou University,No.2023ZZUJGXM114.
文摘BACKGROUND Early symptoms of hepatocellular carcinoma(HCC)are not obvious,and more than 70%of which does not receive radical hepatectomy,when first diagnosed.In recent years,molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC(aHCC).Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected.Signal intensity of intrahepatic nodules was measured,and the hepatobiliary relative enhancement ratio(RER)was calculated.Progression-free survival(PFS)of patients with high and low reinforcement of HCC nodules was compared.The model was validated using receiver operating characteristic curves.Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.RESULTS Univariate and multivariate analyses revealed that the RER,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy(P<0.05).The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876(95%confidence interval:0.781-0.971,P<0.05),the optimal cutoff value was 0.904,diagnostic sensitivity was 87.5%,and specificity was 79.2%.Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio<5,plateletto-lymphocyte ratio<300,prognostic nutritional index<45,and RER<0.9 significantly improved PFS.CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS.Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.
基金Supported by the Lianyungang Comprehensive Cancer Management and Technology Advancement Project,No.QN202302the First People’s Hospital of Lianyungang Young Talent Development Initiative,No.QN2212Jiangsu Society of Research Hospital Translational Medicine Research Grant,No.2024-GDZXKT-01-07.
文摘Primary liver cancer is the sixth most prevalent malignancy worldwide and the third leading cause of cancer-related death.According to the latest data from the National Cancer Center of China,its mortality rate has risen,making it the country’s second-deadliest tumor.Hepatocellular carcinoma(HCC),the predo-minant histological subtype,remains a substantial therapeutic challenge.Hepa-tectomy is the treatment of choice for HCC;however,because of its insidious onset and aggressive progression,the global 5-year survival rate is only 14.1%,and up to 70%of patients experience recurrence within five years after surgery.Consequently,reducing postoperative recurrence and prolonging survival have become critical research priorities.Currently,no consensus or guidelines exist regarding the clinical efficacy or potential synergistic effects of diagnostic and therapeutic strategies to prevent postoperative recurrence.In recent years,interest has grown in systemic therapies and combined local modalities-particularly targeted agents and immune checkpoint inhibitors,as adjuvant treatments.This review synthesizes recent advances in targeted and immunotherapeutic adjuvant therapies for postoperative HCC to inform clinical practice and improve patient outcomes.
文摘This manuscript provides a comprehensive review and highlights of the 2015 San Antonio Breast Cancer Symposium by the leading breast cancer specialists and investigators in the field.
