Search

De-Yi Liu,1,* Yi-Nan Li,1,* Jia-Yi Wu,1,2 Zhen-Xin Zeng,1 Yang-Kai Fu,1 Han Li,1 Xiang-Ye Ou,1 Zhi-Bo Zhang,3 Shuang-Jia Wang,4 Jun-Yi Wu,1,2 Mao-Lin Yan1,2 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217130 ; +86 591-88217140, Fax +86 591-87557768, Email 1248087863@qq.com; yanmaolin74@163.comPurpose: The prognosis of hepatocellular carcinoma (HCC) with extrahepatic metastases (EM) is poor. The efficacy and safety of transcatheter arterial chemoembolization combined with lenvatinib plus anti-programmed cell death 1 inhibitors (triple therapy) for HCC with EM remains unclear. In this study, we aimed to determine the efficacy and safety of triple therapy in HCC patients with EM.Patients and Methods: This study retrospectively reviewed HCC patients with EM who received triple therapy and analyzed their survival rate using the Kaplan–Meier method. Univariate prognostic analysis of each data point was performed using the Log rank test, and multivariate prognostic analysis was performed using the Cox proportional risk regression model.Results: Among 60 HCC patients with EM who underwent triple therapy, the most common sites of metastasis were as follows (in descending order): the lungs (n=27), lymph nodes (n=22), and bones (n=10). After triple therapy, the median progression-free survival and median overall survival were 6 and 18.63 months, respectively. The 6-month, 1-year, and 2-year cumulative survival rates were 87.7%, 68.6%, and 26.8%, respectively. In the multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) ≥ 4 and alpha-fetoprotein (AFP) level ≥ 400 ng/mL were independently associated with overall survival.Conclusion: Our findings revealed that triple therapy is an effective, well-tolerated regimen for HCC patients with EM. AFP level and NLR are prognostic risk factors for triple therapy in this patient population.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, lenvatinib, alpha-fetoprotein, neutrophil-to-lymphocyte ratio

Zhong-Tai Lin,1,2,* Shao-Ming Wei,1,3,* Jun-Yi Wu,1,3,* Zhi-Bo Zhang,4 Shuang-Jia Wang,5 Jian-Yin Zhou,6 Meng-Chao Luo,1,3 Zhen-Xin Zeng,1 Xiang-Ye Ou,1 Yang-Kai Fu,1 Han Li,1 De-Yi Liu,1 Jia-Yi Wu,1,3 Mao-Lin Yan1,3 1The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 0591-88217140, Fax +86 0591-87557768, Email tyhjwjy@163.com; yanmaolin74@163.comBackground: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229– 1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119– 1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092– 0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079– 0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373– 4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147– 372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.Keywords: unresectable, hepatocellular carcinoma, conversion therapy, adjuvant therapy, recurrence-free survival, overall survival

Shu-Qun Li,1– 3,* Jun-Yi Wu,1,2,* Jia-Yi Wu,1,2,* Huang Xie,4,* Jin-Hai Li,1,2 Zhen-Xin Zeng,1,2 Yang-Kai Fu,1,2 De-Yi Liu,1,2 Han Li,1,2 Wei-Zhao Chen,1,2 Jing-Yao Huang,4 Mao-Lin Yan1,2 1Department of Hepatobiliary Pancreatic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, 450001, People’s Republic of China; 4Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Lin Yan; Jing-Yao Huang, Tel +86 591-88217130 ; +86 13705962563, Fax +86 591-87557768 ; +86 591-87113828, Email yanmaolin74@163.com; hjy999@126.comPurpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4).Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan–Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.Results: Median follow-up duration was 18 (4.0– 26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8– 30.5) months, whereas the median PFS was 14.5 (range, 1.3– 27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred.Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.Keywords: transarterial chemoembolization, lenvatinib, programmed death 1 inhibitor, hepatic cellular carcinoma, main trunk portal vein, triple therapy

Meng-Chao Luo,1,2,&ast; Jia-Yi Wu,1,3,&ast; Jun-Yi Wu,1,3 Zhong-Tai Lin,1,2 Yi-Nan Li,3 Zhen-Xin Zeng,3 Shao-Ming Wei,1,2 Mao-Lin Yan1,3 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of General Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217130, Fax +86 591-87557768, Email yanmaolin74@163.com Shao-Ming Wei, Department of General Surgery, Fujian Provincial Hospital, Jinrong South Road 516, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88618707, Fax +86 591-88618900, Email 67468424@qq.comPurpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy.Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration > 50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS).Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991– 45.950, p< 0.001; high-DCP group: OR: 17.853; 95% CI: 4.478– 71.179, p< 0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p< 0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p< 0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p< 0.001).Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of > 50% predicts better treatment outcomes in uHCC patients.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, des-gamma-carboxyprothrombin, combination therapy, tumor response