1.Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma.
Chinese Journal of Internal Medicine 2023;62(7):785-801
		                        		
		                        			
		                        			Transarterial interventional therapy is one of the most widely used treatment methods in patients with primary hepatocellular carcinoma. With the progress in interventional technology and the use of new drugs, transarterial interventional therapy has achieved favorable results in the treatment of primary hepatocellular carcinoma and has become the first choice non-surgical treatment for advanced liver cancer. However, at present, there are great differences in the drugs used in transarterial interventional treatment and the combined application of other drugs among centers, and there is no uniform consensus or guideline. Based on the latest research data and clinical practice experience, as well as the characteristics of Chinese patients, the Specialist Group of Interventional Drugs, Interventionalists Branch of the Chinese Medical Doctor Association was organized to formulate the Chinese expert consensus on intra-arterial drug and combined drug administration for primary hepatocellular carcinoma. The purpose of this consensus is to explore the efficacy and safety of drugs and drug combinations related to intra-arterial interventional therapy, the use of drugs in special populations, the management of adverse reactions, and adjuvant drugs to provide a reference for clinical practice.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular/pathology*
		                        			;
		                        		
		                        			Consensus
		                        			;
		                        		
		                        			East Asian People
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
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		                        			Pharmaceutical Preparations
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		                        			Infusions, Intra-Arterial/methods*
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Drug Therapy, Combination/methods*
		                        			
		                        		
		                        	
2.Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma.
Ling QI ; Bo ZHANG ; Yun LIU ; Lan MU ; Qun LI ; Xi WANG ; Jian Ping XU ; Xing Yuan WANG ; Jing HUANG
Chinese Journal of Oncology 2023;45(3):259-264
		                        		
		                        			
		                        			Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Esophageal Squamous Cell Carcinoma/drug therapy*
		                        			;
		                        		
		                        			Esophageal Neoplasms/pathology*
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Programmed Cell Death 1 Receptor/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/adverse effects*
		                        			;
		                        		
		                        			Liver Diseases/etiology*
		                        			
		                        		
		                        	
3.Status and challenges of neoadjuvant immunotherapy for hepatocellular carcinoma.
Yong Xiang XIA ; Heng Song CAO ; Wei Wei TANG ; Xue Hao WANG
Chinese Journal of Surgery 2023;61(1):7-12
		                        		
		                        			
		                        			With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular/pathology*
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
		                        			;
		                        		
		                        			Immunotherapy
		                        			
		                        		
		                        	
4.Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma.
Chinese Journal of Hepatology 2023;31(1):35-41
		                        		
		                        			
		                        			What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
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		                        			Cholangitis, Sclerosing/diagnosis*
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		                        			Constriction, Pathologic/complications*
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		                        			In Situ Hybridization, Fluorescence
		                        			;
		                        		
		                        			Cholangiocarcinoma/therapy*
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		                        			Liver Diseases/complications*
		                        			;
		                        		
		                        			Cholestasis
		                        			;
		                        		
		                        			Inflammatory Bowel Diseases/therapy*
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		                        			Bile Ducts, Intrahepatic/pathology*
		                        			;
		                        		
		                        			Bile Duct Neoplasms/therapy*
		                        			
		                        		
		                        	
5.Chinese expert consensus on neoadjuvant therapy for hepatocellular carcinoma (2023 edition).
Chinese Journal of Surgery 2023;61(12):1035-1045
		                        		
		                        			
		                        			Recurrence of hepatocellular carcinoma (HCC) after surgery is a major factor affecting the efficacy of the treatment of patients. Neoadjuvant treatment is an effective therapeutic method to reduce postoperative recurrence and prolong patient survival. However,there is no generally accepted neoadjuvant treatment regimen that has been proven to be effective so far. Recently,with the progress in systemic antitumor therapies,represented by targeted molecular agents and immune checkpoint inhibitors,and the improvement in local regional therapies,these treatment approaches have shown promising efficacy and safety in the field of neoadjuvant treatment for HCC. Under the organizational leadership of Committee of Digestive Surgery of Chinese Research Hospital Association and Committee of Liver Cancer of Chinese Anti-Cancer Association,Alliance of Chinese Expert Consensus on Neoadjuvant Therapy for Hepatocellular Carcinoma has discussed and revised several times and finally formulated the Chinese expert consensus on neoadjuvant therapy for hepatocellular carcinoma (2023 edition). This consensus aimed to review the Chinese characteristics of the diagnosis and treatment of HCC,to provide specific guidance and suggestions for preoperative treatment strategies for HCC,and further promote the management of the clinical pathway for neoadjuvant treatment of HCC.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Antineoplastic Agents/therapeutic use*
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		                        			Carcinoma, Hepatocellular/surgery*
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Consensus
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			
		                        		
		                        	
6.Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors.
Kaili YANG ; Jiarui LI ; Lin ZHAO ; Zhao SUN ; Chunmei BAI
Frontiers of Medicine 2022;16(5):773-783
		                        		
		                        			
		                        			The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors (ICIs) in China has not been quantified. This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology. A total of 11 ICIs were recommended for 17 cancer types. The estimated number of eligible patients annually was 1 290 156 (55.18%), which included 888 738 males (60.05%) and 400 468 females (46.67%). The estimated number of responders annually was 448 972 (19.20%), which included 309 023 males (20.88%) and 139 764 females (16.29%). Gastric cancer (n=291 000, 12.45%), non-small-cell lung cancer (n=289 629, 12.39%), and hepatocellular carcinoma (n=277 100, 11.85%) were the top three cancer types with the highest number of eligible patients. Non-small-cell lung cancer (n=180 022, 7.70%), hepatocellular carcinoma (n=75 648, 3.24%), and small-cell lung cancer (n=64 362, 2.75%) were the top three cancer types with the highest number of responders. In conclusion, ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Carcinoma, Non-Small-Cell Lung/pathology*
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		                        			Immune Checkpoint Inhibitors/therapeutic use*
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		                        			Lung Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Antineoplastic Agents, Immunological/therapeutic use*
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular
		                        			;
		                        		
		                        			Liver Neoplasms
		                        			
		                        		
		                        	
7.The companion diagnostics of targeted therapy and immunotherapy for hepatocellular carcinoma.
Xiao Wen HUANG ; Shu Hong LIU ; Jing Min ZHAO
Chinese Journal of Hepatology 2022;30(9):912-917
		                        		
		                        			
		                        			Hepatocellular carcinoma (HCC) has a high incidence and low five-year survival rate in China. There is a lack of effective therapeutic approaches available for unresectable patients with advanced HCC. Recently, the development of targeted and immunotherapy agents and their application in the therapy of various solid tumors have brought new options and benefits to patients with advanced HCC. Companion diagnostics (CDx) emerged with the development of targeted agents, and its roles in selecting eligible patients for specific targeted/immunotherapy agents and improving prognosis are getting more prominent. This article focuses on the CDx technologies and applications related to HCC targeting and immunotherapy, in order to provide inspiration for the precise diagnosis and treatment of HCC.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Carcinoma, Hepatocellular/pathology*
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
		                        			;
		                        		
		                        			Immunotherapy
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Molecular Targeted Therapy
		                        			
		                        		
		                        	
8.Introduction to the recommendations from the European Association for the Study of the Liver clinical practice guidelines on the management of cystic liver disease.
Chen LIANG ; Su Jun ZHENG ; Zhong Ping DUAN
Chinese Journal of Hepatology 2022;30(9):931-933
		                        		
		                        			
		                        			The diagnosis of cystic liver disease has made great progress with the advent of enhanced imaging techniques. At the same time, its management has gradually improved over the past few decades, providing the basis for the development of appropriate diagnostic and treatment guidelines. To this end, the European Association for the Study of the Liver has developed clinical guidelines for the diagnosis and treatment of non-infectious cystic liver disease. This guideline put forward recommendations based on an in-depth review of the relevant literature for addressing clinical issues, including the diagnosis and treament of hepatic cysts, hepatic mucocystic tumors, biliary hamartomas, polycystic liver disease, Caroli disease or Caroli syndrome, biliary hamartomas, and peribiliary cyst.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Liver Diseases/pathology*
		                        			;
		                        		
		                        			Cysts/pathology*
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		                        			Caroli Disease/diagnosis*
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		                        			Liver Neoplasms/therapy*
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		                        			Hamartoma
		                        			
		                        		
		                        	
9.Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase Ⅰ study.
Li ZHANG ; Ji Fang GONG ; Hong Ming PAN ; Yu Xian BAI ; Tian Shu LIU ; Ying CHENG ; Ya Chi CHEN ; Jia Ying HUANG ; Ting Ting XU ; Fei Jiao GE ; Wan Ling HSU ; Jia SHI ; Xi Chun HU ; Lin SHEN
Journal of Peking University(Health Sciences) 2022;54(5):971-980
		                        		
		                        			OBJECTIVE:
		                        			To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC).
		                        		
		                        			METHODS:
		                        			This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC).
		                        		
		                        			RESULTS:
		                        			This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified.
		                        		
		                        			CONCLUSION
		                        			Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Antibodies, Monoclonal, Humanized
		                        			;
		                        		
		                        			Antineoplastic Agents/therapeutic use*
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular/drug therapy*
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		                        			Cisplatin/therapeutic use*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Liver Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Lung Neoplasms/pathology*
		                        			;
		                        		
		                        			Nasopharyngeal Neoplasms/drug therapy*
		                        			
		                        		
		                        	
10.A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study.
Juxian SUN ; Chang LIU ; Jie SHI ; Nanya WANG ; Dafeng JIANG ; Feifei MAO ; Jingwen GU ; Liping ZHOU ; Li SHEN ; Wan Yee LAU ; Shuqun CHENG
Chinese Medical Journal 2022;135(19):2338-2343
		                        		
		                        			BACKGROUND:
		                        			Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC).
		                        		
		                        			METHODS:
		                        			We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage.
		                        		
		                        			RESULTS:
		                        			From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P  < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P  < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P  = 0.001) and 0.474 (0.314-0.717; P  < 0.001) after adjusting for potential confounders, respectively.
		                        		
		                        			CONCLUSION
		                        			ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Carcinoma, Hepatocellular/drug therapy*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Liver Neoplasms/pathology*
		                        			;
		                        		
		                        			Oxaliplatin/therapeutic use*
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		                        			Fluorouracil/adverse effects*
		                        			;
		                        		
		                        			Disease Progression
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Leucovorin/adverse effects*
		                        			;
		                        		
		                        			Colorectal Neoplasms/drug therapy*
		                        			
		                        		
		                        	
            
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