Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarte...Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate...BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting angiogenesis.Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove efficacy.Lenvatinib,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE.However,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been investigated.AIM To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced HCC.METHODS A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022.Baseline characteristics were compared,and propensity score matching was applied.Overall survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were analyzed.RESULTS The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L group.The TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were reported.CONCLUSION TACE+SL demonstrated superior outcomes in terms of OS and PFS,compared to TACE+L.These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.展开更多
BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)var...BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)vary considerably among patients receiving this therapy.AIM To identify predictive biomarkers in HCC patients treated with sintilimab(programmed cell death protein-1 inhibitor)plus lenvatinib(tyrosine kinase inhibitor).METHODS In this single-center study in China,patients with unresectable HCC received sintilimab every 21 days and daily oral lenvatinib.Treatment response was assessed by modified response evaluation criteria in solid tumors.Tumor biopsies underwent RNA sequencing,immune microenvironment profiling,and whole-exome sequencing.Differentially expressed genes(DEGs)and immune cell subsets between response groups were identified,followed by survival analyses.All potential predictors of PFS,together with clinical variables,were included in Cox regression to identify independent prognostic factors.RESULTS Between August 2019 and November 2021,33 patients with hepatitis-B-virus-related HCC were enrolled;by January 2024,13 had undergone potentially curative surgery or ablation.RNA sequencing identified 94 DEGs between responders(n=22)and non-responders(n=11)using Fisher’s exact test or Wilcoxon rank-sum test(all P<0.05).High long intergenic non-protein coding RNA 01554(LINC01554)and whirlin expression were associated with longer PFS in Kaplan-Meier analysis(P<0.05).DEG-immune cell analysis showed positive correlations with pro-B and plasma cells in responders,and negative correlations with CD4+central memory T(Tcm),T helper 1,and natural killer T cells in non-responders;none significantly predicted PFS,although CD4+Tcm cells approached significance(P<0.10).Whole-exome sequencing revealed Fanconi anemia complementation group D2 mutations enriched in non-responders(P<0.05),while cut-like homeobox 1 mutations predicted poorer PFS(P=0.011).Cox regression identified solitary tumor[P=0.02,hazard ratio(HR)=0.31],high LINC01554(P=0.01,HR=0.16),and elevated CD4+Tcm cells(P=0.05,HR=0.29)as independent predictors of prolonged PFS.CONCLUSION Sintilimab plus lenvatinib showed heterogeneous efficacy in HCC.High LINC01554 expression,elevated CD4+Tcm cells,and solitary tumors may serve as predictive biomarkers for prolonged disease control.展开更多
BACKGROUND Inflammation is closely related to survival and disease progression in patients with cancer.However,the predictive value of inflammation-based scores for survival in patients with hepatocellular carcinoma(H...BACKGROUND Inflammation is closely related to survival and disease progression in patients with cancer.However,the predictive value of inflammation-based scores for survival in patients with hepatocellular carcinoma(HCC)treated with Lenvatinib has not been fully elucidated.AIM To compare different inflammation scores'prognostic values,and establish novel nomogram for predicting overall survival(OS)in HCC patients on Lenvatinib.METHODS In total,144 patients with HCC treated with Lenvatinib were enrolled in this study.The prognostic value of pre-treatment inflammation-based scores was retrospectively analyzed,including the platelet-to-lymphocyte ratio,neutrophil-to-lymphocyte ratio,lymphocyteto-C-reactive protein ratio,lymphocyte-to-monocyte ratio,systemic immune-inflammation index,C-reactive protein-to-albumin ratio,and prognostic nutritional index(PNI).Kaplan-Meier survival curves and time-dependent receiver operating characteristic analysis were used to assess predictive accuracy.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors predicting OS and construct a prognostic nomogram.RESULTS All the inflammation-based scores demonstrated good discrimination in terms of OS(all P<0.05),and the PNI emerged as an independent predictor of OS in multivariate analysis(hazard ratio=4.097;95%confidence interval:1.405-11.944;P=0.01).We selected three independent prognostic factors(macrovascular invasion,metastasis,and PNI)to generate a nomogram for OS.CONCLUSION The PNI is a prognostic indicator for assessing OS in patients with HCC treated with Lenvatinib and is superior to other inflammation-based scores in predicting OS.展开更多
BACKGROUND Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma(uHCC).The efficacy of which of them is better suited to combine transarte...BACKGROUND Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma(uHCC).The efficacy of which of them is better suited to combine transarterial chemoembolization(TACE)for the treatment of uHCC is ripe.RESULTS A total of six studies involving 547 patients were included,248 in the TACE-lenvatinib group and 299 in the TACE-sorafenib group.Meta-analysis results showed that TACE-lenvatinib was more effective than TACE-sorafenib in complete response[relative risk(RR)=1.81,95%confidence interval(CI):1.11-2.96,P=0.02],partial response(RR=1.38,95%CI:1.12-1.70,P=0.002),objective response rate(RR=1.47,95%CI:1.24-1.74,P<0.0001)and disease control rate(RR=1.22,95%CI:1.00-1.49,P=0.05).TACE-lenvatinib was significantly lower than TACE-sorafenib in progressive disease rate(RR=0.54,95%CI:0.39-0.74,P=0.002).No significant difference was found in stable disease rate(RR=0.89,95%CI:0.60-1.33,P=0.58)between the two groups.TACE-lenvatinib was significantly more effective than TACE-sorafenib in overall survival(hazard ratio=2.00,95%CI:1.59-2.50,P<0.05)and progression free survival(hazard ratio=2.04,95%CI:1.49-2.86,P<0.05).As regards adverse events,TACE-lenvatinib was better in reducing the incidence of hypertension than TACE-sorafenib,while no significant difference was found in overall adverse events,abdominal pain,fever,fatigue,nausea and vomiting,decreased appetite,liver dysfunction,hand-foot skin reaction,diarrhea,thrombocytopenia,and rash between the two groups.CONCLUSION In patients with uHCC,TACE-lenvatinib induced a better tumor response rate and survival outcome than TACE-sorafenib,while TACE-lenvatinib resulted in a higher incidence of hypertension than TACE-sorafenib.However,these conclusions are derived from currently available medical evidence,and further confirmation by more rigorously designed randomized controlled studies is still needed.展开更多
In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and adva...In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular carcinoma.The triple therapy,which integrates interventional therapy,targeted therapy,and immunotherapy,has emerged as a promising research focus in the treatment of liver cancer.Consequently,it is of utmost significance to select an appropriate combination of interventional therapy,targeted therapy,and immunotherapy for patients suffering from intermediate and advanced liver cancer.展开更多
BACKGROUND Although the triple therapy of transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors and tyrosine kinase inhibitors is becoming an effective treatment for unresectable hepatocellul...BACKGROUND Although the triple therapy of transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors and tyrosine kinase inhibitors is becoming an effective treatment for unresectable hepatocellular carcinoma(uHCC).However,there is still a lack of effective tools for predicting therapeutic effects at present.AIM To develop a predictive tool for the prognosis of uHCC patients treated with TACE,sintilimab and lenvatinib.METHODS Based on multicenter data,this study constructed and validated an AADN score as variables to predict overall survival in patients treated with this combination therapy.This study included 188 uHCC cases(training cohort:n=101,validation cohort:n=87)from three different hospitals.Who were treated with TACE,sintilimab and lenvatinib.RESULTS In multivariate analysis,alpha-fetoprotein≥100 ng/mL[hazard ratio(HR)=2.579,P=0.010],alkaline phosphatase>120 U/L,(HR=2.234,P=0.021),direct bilirubin>7.3μmol/L(HR=2.931,P=0.007)and neutrophil to lymphocyte ratio>2.5(HR=3.127,P=0.006)were identified as independent prognostic factors and were used to establish the AADN score.Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were used to assess the accuracy of the AADN score,with area under receiver operating characteristic curve values of 0.827(training cohort,95%confidence interval:0.743-0.911)and 0.832(validation cohort,95%confidence interval:0.742-0.923).According to the score,the patients were divided into low-risk,intermediate-risk and highrisk groups.Overall survival and progression-free survival were significantly different between groups.CONCLUSION The AADN score can distinguish the prognostic risk of uHCC patients treated with TACE,sintilimab and lenvatinib,provides a basis for individualized treatment decision-making,and have clinical application prospect.展开更多
BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as le...BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.展开更多
BACKGROUND Transcatheter arterial chemoembolization(TACE)combined with lenvatinib is an important modality for the treatment of unresectable hepatocellular carcinoma(HCC).To date,no prognostic analysis exists for clin...BACKGROUND Transcatheter arterial chemoembolization(TACE)combined with lenvatinib is an important modality for the treatment of unresectable hepatocellular carcinoma(HCC).To date,no prognostic analysis exists for clinical predictive models of TACE combined with lenvatinib in treating advanced unresectable HCC.A model was constructed through meta-analysis,and its validation was further enhanced by the collection of external clinical data,thereby providing guidance for clinical practice.AIM To identify risk factors for unresectable HCC following TACE plus lenvatinib therapy and to construct a clinical prediction model.METHODS We searched PubMed,Web of Science,EMBASE,and Cochrane Library databases for studies on TACE plus lenvatinib for unresectable HCC.Risk factors from the meta-analysis and sensitivity analyses were used to construct a prediction model.The validation set included clinical data from 106 eligible patients at the Affiliated Hospital of North Sichuan Medical College collected by June 1,2023.RESULTS This study included 43 group studies involving 5070 patients.Tumor number,microvascular invasion,Eastern Cooperative Oncology Group performance status,Child-Pugh stage,Barcelona Clinic Liver Cancer stage,extra-hepatic metastases,alpha-fetoprotein level,and hepatitis B virus status were risk factors for overall survival and progression-free survival,while triple therapy was a protective factor for both.In the validation set,the overall survival prediction model had area under the curve values of 0.616,0.643,and 0.706 at 1 year,2 years,and 3 years,respectively,and the progression-free survival model had area under the curve values of 0.702,0.696,and 0.670 at the corresponding time points,demonstrating good model performance.Calibration curves,Kaplan-Meier survival analysis,and decision curves further validated the efficacy of the model.CONCLUSION Models based on nine variables from 43 group studies predicted the efficacy of TACE plus lenvatinib in unresectable HCC,supporting evidence-based clinical decisions and treatment strategies.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy in China,primarily diagnosed at advanced stages,which limits treatment options and increases mortality rates.Conversion therapy,which includes systemic...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy in China,primarily diagnosed at advanced stages,which limits treatment options and increases mortality rates.Conversion therapy,which includes systemic and locoregional treatments,aims to render unresectable tumors resectable.Nonetheless,research is scant on the risks of disease progression during the temporary cessation of targeted drugs and immune checkpoint inhibitors before surgery.CASE SUMMARY This report describes a 58-year-old male with HCC who developed lung meta-stases following the discontinuation of lenvatinib and tislelizumab,revealing the necessity for further investigation into the management of HCC patients during the perioperative period,particularly concerning the timing and duration of tar-geted therapy and immunotherapy.CONCLUSION Our study highlights the complex challenges in managing advanced HCC and emphasizes the critical need for ongoing research to refine treatment strategies and improve patient outcomes.展开更多
Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced live...Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced liver cancer who visited from January 2022 to January 2025 were selected as samples and randomly divided into two groups.Group A received interventional therapy combined with lenvatinib and sintilimab,while Group B received interventional therapy combined with lenvatinib.Disease remission rate,adverse reactions,liver function indicators,and tumor marker indicators were compared between the two groups.Results:The disease control rate(DCR)in Group A was higher than that in Group B(P<0.05).There was no difference in adverse reaction rates between Group A and Group B(P>0.05).Total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in Group A were lower than those in Group B(P<0.05).Carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),and alpha-L-fucosidase(AFU)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:Intermediate and advanced liver cancer patients receiving interventional therapy combined with lenvatinib and sintilimab showed reduced tumor marker levels,lessened liver function damage,and a high disease control rate and treatment safety.展开更多
Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary informati...Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.展开更多
BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,surv...BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,survival outcomes remain suboptimal.We hypothesize that TACE-L plus programmed cell death protein-1 inhibitors(TACE-L-P)may offer superior survival benefits compared to TACE-L in this patient population.AIM To compare efficacy and safety of TACE-L-P vs TACE-L in HCC-PVTT and identify prognostic factors.METHODS Data from HCC-PVTT patients treated with TACE-L-P or TTACE-L from January 2018 to December 2023 were collected and retrospectively analyzed.Propensity score matching(PSM)method with optimal matching was used to minimize confounding bias.Overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and treatment-related adverse events(AEs)were compared between the two groups.Independent prognostic factors for OS and PFS were elucidated using the Cox proportional hazards model.RESULTS A total of 100 patients were included,with 42 patients in the TACE-L-P group and 68 patients in the TACE-L group.After PSM performing optimal matching,baseline characteristics were well balanced between the two groups,each comprising 42 patients.The median OS was significantly longer in the TACE-L-P group compared to the TACE-L group(17.2 months vs 12.6 months,P=0.0207),as was the median PFS(10.6 months vs 7.1 months,P=0.012).The ORR and disease control rate were both superior in the TACE-L-P group compared to the TACE-L group(66.7%vs 42.9%,P=0.049;78.6%vs 50.0%,P=0.012).Multivariate analysis revealed that the independent prognostic factors for both OS and PFS were the treatment regimen and extrahepatic metastasis.The incidence of any-grade and grade 3 AEs was comparable between the TACE-L-P and TACE-L groups(84.5%vs 88.1%,P=0.546),with no occurrences of grade 4/5 AEs or treatment-related mortality in either group.CONCLUSION Compared to TACE-L,the TACE-L-P regimen exhibits an acceptable safety profile and shows potential in improving survival outcomes,making it a promising therapeutic option for patients with HCC-PVTT.展开更多
BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity cu...BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve(TIC) of arterial phase on contrastenhanced ultrasound(CEUS) as early imaging biomarkers of lenvatinib efficacy.AIM To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC.METHODS We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors(m RECIST). CEUS was performed at baseline before treatment(Day 0) and on day 7(Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in(Slope),time to peak(TTP) intensity, and the total area under the curve(AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on m RECIST.RESULTS The rate of change for all TIC parameters showed significant differences between the responders(n = 9) and non-responders(n = 11)(Slope, P = 0.025; TTP, P =0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and0.939, respectively.CONCLUSION CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC.展开更多
BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibito...BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.展开更多
BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are ...BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are etiological differences.This necessitates further real-world studies of lenvatinib across diverse populations,such as in China.AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy.Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.Baseline characteristics and adverse events(AEs)were recorded throughout the entire study.RESULTS In total,54 HCC patients treated with lenvatinib monotherapy were included for final analysis.The objective response rate was 22%(n=12)with a progressionfree survival(PFS)of 168 d;however,AEs occurred in 92.8%of patients.Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage[hazard ratio(HR)0.465;95%CI:0.23-0.93;P=0.031],portal vein tumor thrombus(HR 0.38;95%CI:0.15-0.94;P=0.037)and Child-Pugh classifications(HR 0.468;95%CI:and specificity(83.3%)of decreasing serum biomarkers including alphafetoprotein were calculated in order to predict tumor size reduction.Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study.The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC.However,further analysis suggested that baseline characteristics,changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses.Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.展开更多
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
基金supported by grants from the National Natural Science Foundation of China(91959203,82272836 and 82373017)。
文摘Background:The high recurrent rate after surgery hinders the survival of patients with hepatocellular carcinoma(HCC).This prospective cohort study aimed to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization(TACE)as an adjuvant therapy in HCC patients with high risk of recurrence.Methods:Patients were enrolled from eight hepatobiliary centers in China.The primary endpoint was disease-free survival(DFS).The secondary endpoints were overall survival(OS)and safety.Additionally,propensity score matching(PSM)and other three propensity score analyses were performed to balance the potential baseline bias to validate the conclusion.The adverse events(AEs)were recorded throughout the study.The study was registered at Clinical Trials.gov(NCT03838796).Results:A total of 297 patients were enrolled,with 147 in the LEN+TACE group and 150 in the TACE group.Before PSM,the LEN+TACE group achieved significantly better DFS than the TACE group(19.0 vs.10.0 months,P=0.011).PSM analysis identified 111 matched pairs.After PSM,the LEN+TACE group also showed better DFS(19.0 vs.9.0 months,P=0.018).Other three propensity score analyses yielded similar DFS benefit tendency.Furthermore,favorable OS was also obtained in the LEN+TACE group before PSM.Lenvatinib related AEs of grade 3 or 4 occurred in 28.6%of the patients in the LEN+TACE group.Conclusions:Adjuvant lenvatinib plus TACE might be a promising adjuvant approach for HCC patients with high risk of recurrence,which could significantly prolong DFS and potentially OS with a manageable safety profile.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common form of liver cancer that has limited treatment options and a poor prognosis.Transarterial chemoembolization(TACE)is the first-line treatment for intermediate-stage HCC but can induce tumour hypoxia,thereby promoting angiogenesis.Recent studies suggested that combining TACE with anti-angiogenic therapies and immunotherapy might im-prove efficacy.Lenvatinib,a tyrosine kinase inhibitor,has demonstrated superior outcomes compared to sorafenib,while immune checkpoint inhibitors such as sintilimab show potential when combined with TACE.However,the efficacy and safety of TACE combined with lenvatinib and sintilimab(TACE+SL)compared to TACE with lenvatinib alone(TACE+L)in patients with intermediate-ad-vanced HCC has not yet been investigated.AIM To evaluate the efficacy and safety of TACE+SL therapy in comparison to TACE+L therapy in patients with intermediate-advanced HCC.METHODS A retrospective analysis was performed on patients with intermediate-advanced HCC who received TACE plus lenvatinib with or without sintilimab between September 2019 and September 2022.Baseline characteristics were compared,and propensity score matching was applied.Overall survival(OS),progression-free survival(PFS),and objective response rate(ORR)were evaluated between the two groups,and adverse events were analyzed.RESULTS The study included 57 patients,with 30 in the TACE+SL group and 27 in the TACE+L group.The TACE+SL group demonstrated significantly improved median PFS and OS compared to the TACE+L group(PFS:14.1 months vs 9.6 months,P=0.016;OS:22.4 months vs 14.1 months,P=0.039),along with a higher ORR(70.0%vs 55.6%).After propensity score matching,30 patients were included,with the TACE+SL group again showing longer median PFS and a trend toward improved OS(PFS:14.6 months vs 9.2 months,P=0.012;OS:23.9 months vs 16.3 months,P=0.063),and a higher ORR(73.3%vs 53.3%).No severe adverse events were reported.CONCLUSION TACE+SL demonstrated superior outcomes in terms of OS and PFS,compared to TACE+L.These findings suggest that the addition of sintilimab might enhance the therapeutic response in patients with intermediate-advanced HCC.
基金Supported by Clinical Research Fund for Distinguished Young Scholars of Beijing Cancer Hospital,No.LGH2019101 and No.LGH2022005Special Fund for Clinical Research of Wu Jieping Medical Foundation,No.320.6750.19088-38.
文摘BACKGROUND The combination of immune checkpoint inhibitors and antiangiogenic drugs has shown promising efficacy in advanced hepatocellular carcinoma(HCC).However,tumor regression and progression-free survival(PFS)vary considerably among patients receiving this therapy.AIM To identify predictive biomarkers in HCC patients treated with sintilimab(programmed cell death protein-1 inhibitor)plus lenvatinib(tyrosine kinase inhibitor).METHODS In this single-center study in China,patients with unresectable HCC received sintilimab every 21 days and daily oral lenvatinib.Treatment response was assessed by modified response evaluation criteria in solid tumors.Tumor biopsies underwent RNA sequencing,immune microenvironment profiling,and whole-exome sequencing.Differentially expressed genes(DEGs)and immune cell subsets between response groups were identified,followed by survival analyses.All potential predictors of PFS,together with clinical variables,were included in Cox regression to identify independent prognostic factors.RESULTS Between August 2019 and November 2021,33 patients with hepatitis-B-virus-related HCC were enrolled;by January 2024,13 had undergone potentially curative surgery or ablation.RNA sequencing identified 94 DEGs between responders(n=22)and non-responders(n=11)using Fisher’s exact test or Wilcoxon rank-sum test(all P<0.05).High long intergenic non-protein coding RNA 01554(LINC01554)and whirlin expression were associated with longer PFS in Kaplan-Meier analysis(P<0.05).DEG-immune cell analysis showed positive correlations with pro-B and plasma cells in responders,and negative correlations with CD4+central memory T(Tcm),T helper 1,and natural killer T cells in non-responders;none significantly predicted PFS,although CD4+Tcm cells approached significance(P<0.10).Whole-exome sequencing revealed Fanconi anemia complementation group D2 mutations enriched in non-responders(P<0.05),while cut-like homeobox 1 mutations predicted poorer PFS(P=0.011).Cox regression identified solitary tumor[P=0.02,hazard ratio(HR)=0.31],high LINC01554(P=0.01,HR=0.16),and elevated CD4+Tcm cells(P=0.05,HR=0.29)as independent predictors of prolonged PFS.CONCLUSION Sintilimab plus lenvatinib showed heterogeneous efficacy in HCC.High LINC01554 expression,elevated CD4+Tcm cells,and solitary tumors may serve as predictive biomarkers for prolonged disease control.
基金Supported by Natural Science Foundation of China,No.82103566。
文摘BACKGROUND Inflammation is closely related to survival and disease progression in patients with cancer.However,the predictive value of inflammation-based scores for survival in patients with hepatocellular carcinoma(HCC)treated with Lenvatinib has not been fully elucidated.AIM To compare different inflammation scores'prognostic values,and establish novel nomogram for predicting overall survival(OS)in HCC patients on Lenvatinib.METHODS In total,144 patients with HCC treated with Lenvatinib were enrolled in this study.The prognostic value of pre-treatment inflammation-based scores was retrospectively analyzed,including the platelet-to-lymphocyte ratio,neutrophil-to-lymphocyte ratio,lymphocyteto-C-reactive protein ratio,lymphocyte-to-monocyte ratio,systemic immune-inflammation index,C-reactive protein-to-albumin ratio,and prognostic nutritional index(PNI).Kaplan-Meier survival curves and time-dependent receiver operating characteristic analysis were used to assess predictive accuracy.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors predicting OS and construct a prognostic nomogram.RESULTS All the inflammation-based scores demonstrated good discrimination in terms of OS(all P<0.05),and the PNI emerged as an independent predictor of OS in multivariate analysis(hazard ratio=4.097;95%confidence interval:1.405-11.944;P=0.01).We selected three independent prognostic factors(macrovascular invasion,metastasis,and PNI)to generate a nomogram for OS.CONCLUSION The PNI is a prognostic indicator for assessing OS in patients with HCC treated with Lenvatinib and is superior to other inflammation-based scores in predicting OS.
基金Supported by the Shenzhen High-Level Hospital Construction Fund,the Sanming Project of Medicine in Shenzhen,No.SZSM202011010Intramural Research Projects of Shenzhen Hospital,Cancer Hospital,Chinese Academy of Medical Sciences,No.SZ2020MS010the Scientific Research Program Fund of Hunan Provincial Health Commission,No.202204014693.
文摘BACKGROUND Lenvatinib and sorafenib are tyrosine kinase inhibitors that are effective in the treatment of unresectable hepatocellular carcinoma(uHCC).The efficacy of which of them is better suited to combine transarterial chemoembolization(TACE)for the treatment of uHCC is ripe.RESULTS A total of six studies involving 547 patients were included,248 in the TACE-lenvatinib group and 299 in the TACE-sorafenib group.Meta-analysis results showed that TACE-lenvatinib was more effective than TACE-sorafenib in complete response[relative risk(RR)=1.81,95%confidence interval(CI):1.11-2.96,P=0.02],partial response(RR=1.38,95%CI:1.12-1.70,P=0.002),objective response rate(RR=1.47,95%CI:1.24-1.74,P<0.0001)and disease control rate(RR=1.22,95%CI:1.00-1.49,P=0.05).TACE-lenvatinib was significantly lower than TACE-sorafenib in progressive disease rate(RR=0.54,95%CI:0.39-0.74,P=0.002).No significant difference was found in stable disease rate(RR=0.89,95%CI:0.60-1.33,P=0.58)between the two groups.TACE-lenvatinib was significantly more effective than TACE-sorafenib in overall survival(hazard ratio=2.00,95%CI:1.59-2.50,P<0.05)and progression free survival(hazard ratio=2.04,95%CI:1.49-2.86,P<0.05).As regards adverse events,TACE-lenvatinib was better in reducing the incidence of hypertension than TACE-sorafenib,while no significant difference was found in overall adverse events,abdominal pain,fever,fatigue,nausea and vomiting,decreased appetite,liver dysfunction,hand-foot skin reaction,diarrhea,thrombocytopenia,and rash between the two groups.CONCLUSION In patients with uHCC,TACE-lenvatinib induced a better tumor response rate and survival outcome than TACE-sorafenib,while TACE-lenvatinib resulted in a higher incidence of hypertension than TACE-sorafenib.However,these conclusions are derived from currently available medical evidence,and further confirmation by more rigorously designed randomized controlled studies is still needed.
文摘In their study,Han et al compared the efficacy of bevacizumab plus sindilizumab plus interventional therapy with that of lenvatinib plus sindilizumab plus interventional therapy for patients with intermediate and advanced hepatocellular carcinoma.The triple therapy,which integrates interventional therapy,targeted therapy,and immunotherapy,has emerged as a promising research focus in the treatment of liver cancer.Consequently,it is of utmost significance to select an appropriate combination of interventional therapy,targeted therapy,and immunotherapy for patients suffering from intermediate and advanced liver cancer.
基金Supported by National Key Sci-Tech Special Project of China,No.2018ZX10302207Beijing Nova Program,No.20250484965+4 种基金Beijing Natural Science Foundation,No.7222191 and No.7244426Fundamental Research Funds for the Central Universities,Peking University,No.PKU2024XGK005Peking University Medicine Seed Fund for Interdisciplinary Research,No.BMU2021MX007 and No.BMU2022MX001Fundamental Research Funds for the Central Universities,Peking University People’s Hospital Scientific Research Development Funds,No.RDX2020-06 and No.RDJ2022-14the Qi-Min Project.
文摘BACKGROUND Although the triple therapy of transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors and tyrosine kinase inhibitors is becoming an effective treatment for unresectable hepatocellular carcinoma(uHCC).However,there is still a lack of effective tools for predicting therapeutic effects at present.AIM To develop a predictive tool for the prognosis of uHCC patients treated with TACE,sintilimab and lenvatinib.METHODS Based on multicenter data,this study constructed and validated an AADN score as variables to predict overall survival in patients treated with this combination therapy.This study included 188 uHCC cases(training cohort:n=101,validation cohort:n=87)from three different hospitals.Who were treated with TACE,sintilimab and lenvatinib.RESULTS In multivariate analysis,alpha-fetoprotein≥100 ng/mL[hazard ratio(HR)=2.579,P=0.010],alkaline phosphatase>120 U/L,(HR=2.234,P=0.021),direct bilirubin>7.3μmol/L(HR=2.931,P=0.007)and neutrophil to lymphocyte ratio>2.5(HR=3.127,P=0.006)were identified as independent prognostic factors and were used to establish the AADN score.Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were used to assess the accuracy of the AADN score,with area under receiver operating characteristic curve values of 0.827(training cohort,95%confidence interval:0.743-0.911)and 0.832(validation cohort,95%confidence interval:0.742-0.923).According to the score,the patients were divided into low-risk,intermediate-risk and highrisk groups.Overall survival and progression-free survival were significantly different between groups.CONCLUSION The AADN score can distinguish the prognostic risk of uHCC patients treated with TACE,sintilimab and lenvatinib,provides a basis for individualized treatment decision-making,and have clinical application prospect.
基金Supported by the Capital’s Funds for Health Improvement and Research,No.SF202222175.
文摘BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.
文摘BACKGROUND Transcatheter arterial chemoembolization(TACE)combined with lenvatinib is an important modality for the treatment of unresectable hepatocellular carcinoma(HCC).To date,no prognostic analysis exists for clinical predictive models of TACE combined with lenvatinib in treating advanced unresectable HCC.A model was constructed through meta-analysis,and its validation was further enhanced by the collection of external clinical data,thereby providing guidance for clinical practice.AIM To identify risk factors for unresectable HCC following TACE plus lenvatinib therapy and to construct a clinical prediction model.METHODS We searched PubMed,Web of Science,EMBASE,and Cochrane Library databases for studies on TACE plus lenvatinib for unresectable HCC.Risk factors from the meta-analysis and sensitivity analyses were used to construct a prediction model.The validation set included clinical data from 106 eligible patients at the Affiliated Hospital of North Sichuan Medical College collected by June 1,2023.RESULTS This study included 43 group studies involving 5070 patients.Tumor number,microvascular invasion,Eastern Cooperative Oncology Group performance status,Child-Pugh stage,Barcelona Clinic Liver Cancer stage,extra-hepatic metastases,alpha-fetoprotein level,and hepatitis B virus status were risk factors for overall survival and progression-free survival,while triple therapy was a protective factor for both.In the validation set,the overall survival prediction model had area under the curve values of 0.616,0.643,and 0.706 at 1 year,2 years,and 3 years,respectively,and the progression-free survival model had area under the curve values of 0.702,0.696,and 0.670 at the corresponding time points,demonstrating good model performance.Calibration curves,Kaplan-Meier survival analysis,and decision curves further validated the efficacy of the model.CONCLUSION Models based on nine variables from 43 group studies predicted the efficacy of TACE plus lenvatinib in unresectable HCC,supporting evidence-based clinical decisions and treatment strategies.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy in China,primarily diagnosed at advanced stages,which limits treatment options and increases mortality rates.Conversion therapy,which includes systemic and locoregional treatments,aims to render unresectable tumors resectable.Nonetheless,research is scant on the risks of disease progression during the temporary cessation of targeted drugs and immune checkpoint inhibitors before surgery.CASE SUMMARY This report describes a 58-year-old male with HCC who developed lung meta-stases following the discontinuation of lenvatinib and tislelizumab,revealing the necessity for further investigation into the management of HCC patients during the perioperative period,particularly concerning the timing and duration of tar-geted therapy and immunotherapy.CONCLUSION Our study highlights the complex challenges in managing advanced HCC and emphasizes the critical need for ongoing research to refine treatment strategies and improve patient outcomes.
文摘Objective:To observe the control effect of interventional therapy combined with lenvatinib and sintilimab in patients with intermediate and advanced liver cancer.Methods:82 patients with intermediate and advanced liver cancer who visited from January 2022 to January 2025 were selected as samples and randomly divided into two groups.Group A received interventional therapy combined with lenvatinib and sintilimab,while Group B received interventional therapy combined with lenvatinib.Disease remission rate,adverse reactions,liver function indicators,and tumor marker indicators were compared between the two groups.Results:The disease control rate(DCR)in Group A was higher than that in Group B(P<0.05).There was no difference in adverse reaction rates between Group A and Group B(P>0.05).Total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in Group A were lower than those in Group B(P<0.05).Carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),and alpha-L-fucosidase(AFU)levels in Group A were also lower than those in Group B(P<0.05).Conclusion:Intermediate and advanced liver cancer patients receiving interventional therapy combined with lenvatinib and sintilimab showed reduced tumor marker levels,lessened liver function damage,and a high disease control rate and treatment safety.
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.
基金Supported by Zhejiang Province Medicine and Health Science and Technology Project,No.2023KY239Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project,No.2024ZL949.
文摘BACKGROUND Hepatocellular carcinoma with portal vein tumor thrombus(HCC-PVTT)is a severe condition with poor prognosis.While transarterial chemoembolization(TACE)combined with lenvatinib(TACE-L)shows some promise,survival outcomes remain suboptimal.We hypothesize that TACE-L plus programmed cell death protein-1 inhibitors(TACE-L-P)may offer superior survival benefits compared to TACE-L in this patient population.AIM To compare efficacy and safety of TACE-L-P vs TACE-L in HCC-PVTT and identify prognostic factors.METHODS Data from HCC-PVTT patients treated with TACE-L-P or TTACE-L from January 2018 to December 2023 were collected and retrospectively analyzed.Propensity score matching(PSM)method with optimal matching was used to minimize confounding bias.Overall survival(OS),progression-free survival(PFS),objective response rate(ORR),and treatment-related adverse events(AEs)were compared between the two groups.Independent prognostic factors for OS and PFS were elucidated using the Cox proportional hazards model.RESULTS A total of 100 patients were included,with 42 patients in the TACE-L-P group and 68 patients in the TACE-L group.After PSM performing optimal matching,baseline characteristics were well balanced between the two groups,each comprising 42 patients.The median OS was significantly longer in the TACE-L-P group compared to the TACE-L group(17.2 months vs 12.6 months,P=0.0207),as was the median PFS(10.6 months vs 7.1 months,P=0.012).The ORR and disease control rate were both superior in the TACE-L-P group compared to the TACE-L group(66.7%vs 42.9%,P=0.049;78.6%vs 50.0%,P=0.012).Multivariate analysis revealed that the independent prognostic factors for both OS and PFS were the treatment regimen and extrahepatic metastasis.The incidence of any-grade and grade 3 AEs was comparable between the TACE-L-P and TACE-L groups(84.5%vs 88.1%,P=0.546),with no occurrences of grade 4/5 AEs or treatment-related mortality in either group.CONCLUSION Compared to TACE-L,the TACE-L-P regimen exhibits an acceptable safety profile and shows potential in improving survival outcomes,making it a promising therapeutic option for patients with HCC-PVTT.
文摘BACKGROUND Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma(HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve(TIC) of arterial phase on contrastenhanced ultrasound(CEUS) as early imaging biomarkers of lenvatinib efficacy.AIM To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC.METHODS We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors(m RECIST). CEUS was performed at baseline before treatment(Day 0) and on day 7(Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in(Slope),time to peak(TTP) intensity, and the total area under the curve(AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on m RECIST.RESULTS The rate of change for all TIC parameters showed significant differences between the responders(n = 9) and non-responders(n = 11)(Slope, P = 0.025; TTP, P =0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and0.939, respectively.CONCLUSION CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC.
基金Supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,No.2021-I2M-1-061 and 2021-I2M-1-003Chinese Society of Clinical Oncology-Hengrui Cancer Research Fund,No.Y-HR2019-0239+1 种基金Chinese Society of Clinical Oncology-MSD Cancer Research Fund,No.Y-MSDZD2021-0213National Ten-thousand Talent Program.
文摘BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.
基金Supported by the International Science and Technology Cooperation Projects,No.2016YFE0107100the Capital Special Research Project for Health Development,No.2014-2-4012+2 种基金the Beijing Natural Science Foundation,No.L172055 and No.7192158the National Tenthousand Talent Program,the Fundamental Research Funds for the Central Universities,No.3332018032and the CAMS Innovation Fund for Medical Science(CIFMS),No.2017-I2M-4-003 and No.2018-I2M-3-001.
文摘BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are etiological differences.This necessitates further real-world studies of lenvatinib across diverse populations,such as in China.AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy.Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.Baseline characteristics and adverse events(AEs)were recorded throughout the entire study.RESULTS In total,54 HCC patients treated with lenvatinib monotherapy were included for final analysis.The objective response rate was 22%(n=12)with a progressionfree survival(PFS)of 168 d;however,AEs occurred in 92.8%of patients.Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage[hazard ratio(HR)0.465;95%CI:0.23-0.93;P=0.031],portal vein tumor thrombus(HR 0.38;95%CI:0.15-0.94;P=0.037)and Child-Pugh classifications(HR 0.468;95%CI:and specificity(83.3%)of decreasing serum biomarkers including alphafetoprotein were calculated in order to predict tumor size reduction.Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study.The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC.However,further analysis suggested that baseline characteristics,changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses.Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.
