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Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.
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Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.
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Malignant hepatobiliary tumors mainly include hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) and are common malignancies in China that seriously threaten the life and health of the Chinese people. Malignant hepatobiliary tumors often have an insidious onset, and most patients have lost the opportunity for surgery due to the advanced stage at initial diagnosis. The treatment of advanced HCC mainly depends on systemic therapy such as sorafenib, lenvatinib, donafenib, regorafenib, apatinib, and systemic chemotherapy, but such treatment often has a limited effect. The treatment of advanced BTC mainly relies on systemic chemotherapy, which often has an unsatisfactory effect. The advent of the era of immunotherapy brings new hope to the treatment of advanced malignant hepatobiliary tumors. Atezolizumab combined with bevacizumab and sintilimab combined with a bevacizumab biosimilar IBI305 have been approved as the first-line treatment of advanced HCC. The treatment regimens, such as Chemotherapy-based immune checkpoint inhibitor (ICI) or ICI combined with targeted drugs, have made great progress in the treatment of advanced BTC, and although these regimens can significantly improve the overall survival of patients, they often bring obvious and even life-threatening adverse reactions, which should be taken seriously by clinicians. In addition, further studies are needed to investigate the value of ICI-based combination therapy in the perioperative treatment of malignant hepatobiliary tumors.
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The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.
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Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.
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Objective To study the clinical impact of microvascular invasion (MVI) on patients with intrahepatic cholangiocarcinoma (ICC) after R0 resections.Methods The clinicopathological data of 359 patients with ICC who underwent R0 resection in the Zhongshan Hospital,Fudan University between January 2000 and December 2008 were retrospectively studied.Univariate analysis and multivariate analysis were carried out to study factors related to postoperative survival outcomes and recurrence.The impact of MVI on patients with ICC after R0 resection was studied.Results The incidence of MVI was 13.6％ in the study cohort.MVI was correlated with HBV infection (P ＜ 0.05),liver cirrhosis (P ＜ 0.05) and tumor differentiation (P ＜ 0.05).The 1-,3-,5-year overall survival (OS) between the MVI positive and negative groups were 50.0％,20.9％,12.2％ and 63.9％,33.1％,22.0％ respectively (P ＜ 0.05),and the median survival time was 13 months and 18.5 months (P ＜0.05).The 1-,3-,5-year recurrence free survival (RFS) rates between the MVI positive and negative groups were 29.7％,12.7％,8.5％ and 50.6％,26.9％,18.4％,respectively (P ＜0.05),and the median recurrence free survival time was 8 months and 12.5 months (P ＜ 0.05).Multivariate analysis showed that MVI was an independent risk factor affecting recurrence after R0 resection (HR 1.852,95％ CI:1.075 ～ 3.195,P ＜ 0.05).Conclusions The occurrence of MVI in ICC patients was associated with hepatitis B infection.MVI was an independent risk factor affecting recurrence in ICC patients after R0 resection.However,it was not an independent risk factor of overall survival in patients after R0 resection.The clinical impact of MVI on patients with ICC was not as strong as for hepatocellular carcinoma.