MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY ********** DANG TRUNG THANH SUBCLINICAL VALUES IN PROGNOSIS AND MONITORING OF TREATMENT FOR HEPATOCELLULAR CARCINOMA WITH TRANSARTERIAL CHEMOEMBOLIZATION COMBINED WITH RADIOFREQUENCY ABLATION Major Code : Gastroenterology : 62.72.01.43 ABSTRACT OF DOCTORAL DISSERTATION HANOI - 2020 THE WORK ARE COMPLETED AT BACH MAI HOSPITAL AND HANOI MEDICAL UNIVERSITY HOSPITAL Supervisor: Assoc Prof Tran Ngoc Anh Reviewer 1: Tran Viet Tu, M.D, Ph.D Reviewer 2: Le Chinh Dai, M.D, Ph.D Reviewer 3: Vu Truong Khanh, M.D The dissertation is going to be defended in front of the doctoral thesis evaluation committee at Hanoi Medical University The thesis can be found at: Vietnamese National Library Library of Hanoi Medical University INTRODUCTION Hepatocellular carcinoma (HCC) is the 3rd most severe malignancy in terms of mortality in all cancers with approximately 787,200 deaths per year Vietnam is one of the countries with the highest HCC incidence with over 10,000 new cases each year Multidisciplinary treatment of HCC has been gaining attention in recent years, including transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) To study the effectiveness of combination therapy, clinicians also combine imaging diagnosis to monitor treatment efficacy, along with the use of tumor markers, which also play an important role in diagnosing, evaluating treatment results and monitoring the recurrence of HCC In Vietnam, a new set including three markers of AFP, AFPL3 and PIVKA-II was put into use in the diagnosis and evaluation of HCC treatment results To data, very little study in Vietnam reported on the role of these markers, especially the use of GALAD and BALAD models in HCC diagnosis and evaluation Hence, this study was conducted with the aims of: To evaluate diagnostic values of AFP, AFP-L3, PIVKA II and GALAD in HCC To evaluate the values of AFP- L3, PIVKA-II and BALAD in the prognosis and monitoring of treatment outcomes of HCC with transarterial chemoembolization radiofrequency ablation combined with IMPORTANCE OF DOCTORAL DISSERTATION Investigation of the value of AFP, AFP-L3 and PIVKA II markers in HCC patients This study identified cut-off threshold values of AFP, AFP-L3 and PIVKA II markers, GALAD scale for HCC diagnosis Evaluate the values of AFP, AFP-L3 and PIVKA-II, BALAD scale was in prognosis and monitor the effectiveness of treatment of liver tumors by combining transarterial chemoembolization (TACE) with radiofrequency ablation (RFA) We also initially determined the values of AFP-L3, PIVKA II, BALAD, GALAD scores in estimating the life expectancy and treatment response of HCC patients Thereby, the assessment of the response of treatment was according to the Japan Hepatobiliary Association, in Fwhich the proportion of patients responding to treatment was 68.9% FINDINGS OF DOCTORAL DISSERTATION We examined important values of AFP, AFP-L3, and PIVKA II in hepatocellular carcinoma (HCC) To explore cut-off points of AFP, AFP-L3, PIVKA-II, and GALAD in the diagnosis of HCC To evaluate the values of AFP- L3, PIVKA-II and BALAD in the prognosis and monitoring of treatment outcomes of HCC with transarterial chemoembolization combined with radiofrequency ablation The life expectancy of patients with HCC was estimated based on the values of AFP-L3, PIVKA-II, BALAD, and GALAD The proportion of patients responding to treatment was 68.9% according to the Japan Society of Hepatology THESIS STRUCTURE The thesis consists of 140 pages including 02-page introduction, 37page overview, 25-page methods, 37-page results, 36-page discussion, 02-page conclusions, and 01-page recommendation The thesis has 52 tables, 25 illustrations, figures There are 182 references, of which 17 are Vietnamese Chapter OVERVIEW 1.1 Diagnosis and treatment of HCC 1.1.1 Diagnostic criteria of HCC - American Gallbladder Association - European Hepatobiliary Association - Asian and Pacific Liver Association - Japanese Gallbladder Association - Diagnostic criteria for HCC according to the Ministry of Health of Vietnam 1.1.2 Diagnostic criteria of liver hemangioma Hepatic hemangiomas are divided into two main types: cavernous hemangioma and capillary hemangioma, in which most Hepatic hemangiomas are cavernous hemangioma 1.2 Treatment methods of HCC 1.2.1 Liver resection/ liver transplantation Liver resection is the optimal choice for cases of AF, with good liver function even on cirrhosis (Stage T1-3, N0, M0) The widely accepted criteria for liver transplantation is that Child C cirrhosis has liver tumor less than 5cm or has up to tumors with a size of less than 3cm each and has no invasive vascular invasion or extrahepatic metastases (Milan criteria) 1.2.2 Destroy the tumor on the spot Methods to destroy the tumor on the spot include: absolute alcohol injection, high frequency (RFA), and microwave heating 1.2.3 Cut off the tumor blood supply The tumor does not cut or many lobes There may be small portal venous thrombosis Overall score (PS) = 0-2 Child Pugh A, B No distant metastasis 1.3 Subclinical methods used in the diagnosis and monitoring of patients with primary HCC 1.3.1 Image diagnostic methods Ultrasound, CT - scanner, computerized tomography (CT) scan / magnetic resonance imaging (MRI) play the important role in the diagnosis and monitoring of disease status 1.3.2 Markers The tumor markers in HCC are used for the purpose of early diagnosis, prognosis of extra survival and monitoring of treatment It is common to divide tumor markers over several research stages before being routinely used in clinical practice (Phase 1: preclinical studies; Phase 2: clinical trials and cut-off score determination ; Phase 3: retrospective research and vertical tracking; Phase 4: prospective studies; Phase 5: case studies) 1.4 The values of AFP-L3, PIVKA II and GALAD model in monitoring treatment of primary HCC 1.4.1 The effectiveness of HCC treatments combines RFA and TACE TACE in conjunction with RFA TACE is a local destruction therapy by obstructing the blood vessels that feed the tumor and providing local chemotherapy TACE can reduce the cooling effect of large vessels adjacent to the UTBMTBG, resulting in a significant increase in the excision region TACE may also be effective in treating small undetected metastases adjacent to the primary tumor 1.4.2 The values of AFP-L3, PIVKA II and GALAD model Pathogenesis of HCC complex is influenced by many factors, besides the markers being studied in phase and phase Another approach scientists are taking is to combine existing cancer markers in the GALAD or BALAD model to provide better diagnostic and follow-up values Chapter METHODS 2.1 Research objects 2.1.1 Location and time The study was conducted at the Center for Nuclear Medicine and Oncology at Bach Mai Hospital and Hanoi Medical University Hospital from June 2016 to September 2019 2.1.2 Patients The patients were diagnosed with HCC and hepatic hemangiomas 2.1.2.1 Selection criteria Diagnosis of HCC following treatment guidelines of the Ministry of Health in 2012 2.1.2.2 Exclusion criteria The patient is contraindicated to treat with HCC following RFA and TACE therapy 2.2 Methodology 2.2.1 Study design Progressive study 2.2.2 Sample n = Z2(1-α/2)(pxq)/d2 p = 0.1 (with Cut-off AFP value - L3 10%, in patients with small tumors