Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease： More than 2-year Follow-up

Background： Currently, treatment of symptomatic polycystic liver disease （PLD） is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization （TAE） of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate （NBCA） and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up, Methods： Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients （20 women and 3 men; mean age, 49.0 ± 14.5 years） infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. Results： Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months （interquartile range, 30.0-72.0 months）. PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients （four patients did not benefit from TAE）. The mean maximum abdominal circumference decreased significantly from 1 06.0± 8.0 cm to 87.0 ± 15.0 cm （P = 0.021）. The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE （P 〈 0.05）. The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months （P 〈 0.05）. Conclusions： TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

A report of a new late toxic effect of lenvatinib

To the Editor:Hepatocellular carcinoma(HCC)is the third most lethal malignancy globally.[1]Besides sorafenib,lenvatinib is currently the second approved targeted agent for the first-line treatment of HCC in 2018.Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor(VEGF)receptors 1 to 3,fibroblast growth factor receptors 1 to 4,platelet-derived growth factor receptor a,RET,and KIT.[2]Patients who received lenvatinib experienced diarrhoea,and alope and more instances of hypertension,proteinuria,and hypothyroidism.Here,we report two patients that developed irreversible pancreatic atrophy as a novel adverse event of lenvatinib.