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Namba Y, Kobayashi T, Hirata Y, Tadokoro T, Fukuhara S, Oshita K, Honmyo N, Nakano R, Sakai H, Shimizu S, Kuroda S, Tahara H, Ohira M, Ide K, Tanaka Y, Ohdan H. Usefulness of preoperative peripheral blood GPC3-positive circulating tumor cells in subclassification of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma: a retrospective cohort study. Hepatol Res 2025. [PMID: 40372141 DOI: 10.1111/hepr.14211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2025] [Revised: 05/05/2025] [Accepted: 05/08/2025] [Indexed: 05/16/2025]
Abstract
AIM The treatment strategy for hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B, representing the intermediate stage, remains unclear. This study aimed to evaluate the utility of glypican-3 (GPC3)-positive circulating tumor cells (CTCs) in subclassifying BCLC stage B. METHODS The present retrospective cohort study included patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and March 2022. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS). RESULTS A total of 338 patients were included in the analysis. GPC3-positive CTCs were significantly associated with a positive rate of microscopic portal vein invasion. In BCLC stages 0/A, there was no significant difference in survival rates between patients with GPC3-positive CTC counts. However, in BCLC stage B, both OS and RFS were significantly lower in the high number of GPC3-positive CTC group (p = 0.02 and p = 0.03, respectively). Further analysis using a four-group classification based on BCLC stage and GPC3-positive CTC count revealed that both OS and RFS were significantly lower in BCLC stage B with the high number of GPC3-positive CTC group (p < 0.01). Multivariate analysis identified Child-Pugh B status and beyond up-to-7 criteria as independent risk factors for poor OS (p = 0.01 and p = 0.04, respectively). For RFS, beyond up-to-7 criteria and a high number of GPC3-positive CTCs were identified as independent predictive factors (p = 0.04). Based on BCLC stage B, combining GPC3-positive CTCs with the up-to-7 criteria significantly stratified OS and RFS. CONCLUSIONS Glypican-3-positive CTCs are effective for subclassifying BCLC stage B HCC. When combined with the up-to-7 criteria, they may help with the development of new treatment strategies.
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Affiliation(s)
- Yosuke Namba
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshito Hirata
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takeshi Tadokoro
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Sotaro Fukuhara
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ko Oshita
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naruhiko Honmyo
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryosuke Nakano
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Sakai
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Seiichi Shimizu
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroyuki Tahara
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Kim J, Kim JH, Ko E, Kim JY, Im BS, Kim GH, Chu HH, Ko HK, Gwon DI, Shin JH, Alrashidi I. Model Predicting Survival in Intermediate-Stage HCC Patients Reclassified for TACE Based on the 2022 BCLC Criteria. Cancers (Basel) 2025; 17:894. [PMID: 40075741 PMCID: PMC11898427 DOI: 10.3390/cancers17050894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 02/25/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Background/Objectives: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) was updated in 2022 to refine patient stratification, particularly in patients with intermediate-stage (BCLC B) HCC. Although transarterial chemoembolization (TACE) remains a key treatment for these patients, there is no prognostic model for survival outcomes based on the pretreatment factors of patients who meet the updated 2022 BCLC indications for TACE. The aim of this study was to develop a pretreatment risk model predicting overall survival (OS) in patients with intermediate-stage HCC and reclassified as candidates for TACE according to the updated 2022 BCLC criteria. Methods: This retrospective study included 658 HCC patients treated with first-line TACE according to the updated BCLC 2022 guidelines. Pretreatment factors such as the Child-Pugh score, tumor burden (up-to-11 criteria), bilobar tumor involvement, and serum alpha-fetoprotein (AFP) levels were analyzed. Cox proportional hazards models were used to identify significant predictors of OS, with these factors subsequently incorporated into a risk prediction model. Results: Significant predictors of OS included Child-Pugh score ≥ 7, bilobar tumor involvement, beyond up-to-11 criteria, and AFP ≥ 400 ng/mL. A risk model was developed using these factors, stratifying patients into low-, intermediate-, and high-risk groups. The median OS in the low-, intermediate-, and high-risk groups was 53, 35, and 21 months, respectively. Conclusions: The proposed pretreatment risk prediction model may be useful for predicting OS and guiding TACE candidacy in intermediate-stage HCC patients based on the updated 2022 BCLC guidelines.
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Affiliation(s)
- Jihoon Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Jin-Hyoung Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Eunbyul Ko
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Jeong-Yeon Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Byung Soo Im
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Gun Ha Kim
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Hee Ho Chu
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Heung-Kyu Ko
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Dong Il Gwon
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Ji Hoon Shin
- Department of Radiology, Research Institute of Radiology, College of Medicine, Asan Medical Center, University of Ulsan, Seoul 05505, Republic of Korea; (J.K.); (E.K.); (J.-Y.K.); (B.S.I.); (G.H.K.); (H.H.C.); (H.-K.K.); (D.I.G.); (J.H.S.)
| | - Ibrahim Alrashidi
- Department of Radiology, Prince Sultan Military Hospital, Madinah 42375, Saudi Arabia;
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Alhaddad O, Gomaa A, Shamandy ME, Kohla M, Edrees A, Ashour R. Evaluation of different scoring systems for repeating Transarterial Chemoembolization in Egyptian patients with Hepatocellular Carcinoma. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2024; 62:430-439. [PMID: 39217454 DOI: 10.2478/rjim-2024-0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) have a diverse range of outcomes due to their high degree of heterogeneity. Therefore, different predictive scoring systems have been created to assist in decision-making regarding retreatment with TACE. We compared the predictive capabilities of different scoring systems, such as ART, ABCR, and SNACOR, for prediction of the outcome of subsequent TACE in HCC patients. METHOD In this retrospective study, the three scoring systems were compared for their capability of predicting the outcome of repeating TACE in 149 HCC patients treated at the National Liver Institute, Egypt, between January 2017 and December 2019. We used the likelihood ratio to select the model with the highest predictive capability for overall survival (OS). RESULTS According to our data, the amount of tumor, the change in Barcelona Clinic Liver Cancer (BCLC) stage following TACE, and the SNACOR score (with a 95% confidence range for HR 1.0305-1.256 and p-value = 0.0106) were the most predictive variables. It was also shown that the ABCR score was a good predictor of survival (90 patients had an ABCR score ≤ 0 with a P- value <0.0001, 56 patients had 0 < ABCR < 4 with a P-value <0.0001, and the ART score was not useful in predicting OS (P-value = 0.18). CONCLUSION The SNACOR score is the most predictive score for OS and would be the most helpful scoring system in decision-making regarding retreatment with TACE.
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Affiliation(s)
- Omkolsoum Alhaddad
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Asmaa Gomaa
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Merhan El Shamandy
- Department of Hepatology and Gastroenterology, Ahmad Maher Teaching Hospital, Cairo 11511, Egypt
| | - Mohamed Kohla
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Ahmed Edrees
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
| | - Reham Ashour
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, 32511, Egypt
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Bannangkoon K, Hongsakul K, Tubtawee T, Ina N. Prognostic Value of Myosteatosis and Albumin-Bilirubin Grade for Survival in Hepatocellular Carcinoma Post Chemoembolization. Cancers (Basel) 2024; 16:3503. [PMID: 39456597 PMCID: PMC11506580 DOI: 10.3390/cancers16203503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/04/2024] [Accepted: 10/12/2024] [Indexed: 10/28/2024] Open
Abstract
OBJECTIVE This study aimed to investigate the prognostic value of preoperative myosteatosis and the albumin-bilirubin (ALBI) grade in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) and develop a robust prognostic score based on these factors. METHODS Patients with HCC who underwent TACE between January 2009 and December 2020 were included. Multivariate Cox regression analysis identified prognostic factors. CT-based body composition parameters were acquired from baseline abdominal CT images at the level of the third lumbar vertebra. A prognostic score (Myo-ALBI) was developed based on the presence of preoperative myosteatosis and the ALBI grade, and its prognostic value was evaluated. RESULTS Of 446 patients, 63% were male, and the mean age was 62.4 years. Preoperative myosteatosis was present in 41.5% of patients. The BCLC stages were mostly B (67.9%). Multivariate analysis shows that preoperative myosteatosis, ALBI grade 2, and ALBI grade 3 were independent prognostic factors. The Myo-ALBI grade was incorporated into a prognostic model, including alpha-fetoprotein and up-to-seven criteria, to generate a nomogram. The C-index of the nomogram based on the Myo-ALBI grade (0.743) was significantly higher than the non-Myo-ALBI nomogram (0.677), the up-to-seven criteria (0.653), the ALBI grade (0.616), and the Child-Pugh class (0.573) (all p < 0.05). The t-ROC curve for the nomogram was consistently superior to the other models throughout the observation period in all patients and the BCLC-B subgroup. CONCLUSIONS The combination of preoperative CT-derived myosteatosis and ALBI grade enhances prognostication for patients with unresectable HCC undergoing TACE. The Myo-ALBI nomogram constructed in this study could support individualized prognosis prediction, assisting in treatment decision-making for HCC patients.
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Affiliation(s)
- Kittipitch Bannangkoon
- Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Songkhla, Thailand; (K.H.); (T.T.); (N.I.)
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Minozzi S, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments. Dig Liver Dis 2024; 56:223-234. [PMID: 38030455 DOI: 10.1016/j.dld.2023.10.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova- Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Silvia Minozzi
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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Karagiannakis DS. Systemic Treatment in Intermediate Stage (Barcelona Clinic Liver Cancer-B) Hepatocellular Carcinoma. Cancers (Basel) 2023; 16:51. [PMID: 38201479 PMCID: PMC10778557 DOI: 10.3390/cancers16010051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/08/2023] [Accepted: 12/14/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) represents an entity of poor prognosis, especially in cases of delayed diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, patients in BCLC-A are the most suitable for potentially curative treatments (surgery or radiofrequency ablation), whereas those in BCLC-C should be treated only with systemic treatment, as locoregional interventions are ineffective due to the tumor's extensiveness. For patients in the BCLC-B stage, trans-arterial chemoembolization (TACE) is the reference treatment, but the role of systemic treatment has been constantly increasing. As this group of patients is extremely heterogeneous, a case-by-case therapeutic strategy instead of a one-fits-all treatment is certainly required to achieve adequate results against HCC. The decision of selecting among immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), TACE, or a combination of them depends on the patient's tumor load, the severity of liver dysfunction, the general performance status, and the presence of concomitant extrahepatic diseases. The objective of this review is to critically appraise the recent data regarding the systemic treatment of BCLC-B HCCs, aiming to emphasize its potential role in the management of these difficult-to-treat patients.
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Affiliation(s)
- Dimitrios S Karagiannakis
- Academic Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 12462 Athens, Greece
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Omar A, Kaseb A, Elbaz T, El-Kassas M, El Fouly A, Hanno AF, El Dorry A, Hosni A, Helmy A, Saad AS, Alolayan A, Eysa BE, Hamada E, Azim H, Khattab H, Elghazaly H, Tawfik H, Ayoub H, Khaled H, Saadeldin I, Waked I, Barakat EMF, El Meteini M, Hamed Shaaban M, EzzElarab M, Fathy M, Shaker M, Sobhi M, Shaker MK, ElGharib M, Abdullah M, Mokhtar M, Elshazli M, Heikal OMK, Hetta O, ElWakil RM, Abdel Wahab S, Eid SS, Rostom Y. Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2023; 10:1547-1571. [PMID: 37744303 PMCID: PMC10516190 DOI: 10.2147/jhc.s404424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 09/01/2023] [Indexed: 09/26/2023] Open
Abstract
Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.
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Affiliation(s)
- Ashraf Omar
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tamer Elbaz
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Amr El Fouly
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Abdel Fatah Hanno
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed El Dorry
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Amr Helmy
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
| | - Amr S Saad
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ashwaq Alolayan
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
| | - Basem Elsayed Eysa
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Emad Hamada
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hamdy Azim
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hany Khattab
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hesham Elghazaly
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hesham Tawfik
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
| | - Hisham Ayoub
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
| | - Hussein Khaled
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ibtessam Saadeldin
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Imam Waked
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
| | - Eman M F Barakat
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mahmoud El Meteini
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Hamed Shaaban
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed EzzElarab
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed Fathy
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Shaker
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Sobhi
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed Kamal Shaker
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohamed ElGharib
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mohammed Abdullah
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohesn Mokhtar
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mostafa Elshazli
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Osama Hetta
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Reda Mahmoud ElWakil
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sameh Abdel Wahab
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Samir Shehata Eid
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Yousri Rostom
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - On behalf of the Egyptian Liver Cancer Committee Study Group
- Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt
- Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt
- Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Tanta University, TantaEgypt
- Department of Gastroenterology, Military Medical Academy, Cairo, Egypt
- Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt
- Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
- Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Bannangkoon K, Hongsakul K, Tubtawee T. Validation of the ALBI-TAE model and comparison of seven scoring systems for predicting survival outcome in patients with intermediate-stage hepatocellular carcinoma undergoing chemoembolization. Cancer Imaging 2023; 23:51. [PMID: 37248526 DOI: 10.1186/s40644-023-00575-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 05/22/2023] [Indexed: 05/31/2023] Open
Abstract
BACKGROUND The ALBI-TAE model was recently proposed as a scoring system to select suitable patients with intermediate-stage hepatocellular carcinoma (HCC) for transarterial chemoembolization (TACE). However, this scoring system has not been externally validated. Therefore, we validated this score and compared it with six scoring systems in terms of prognostication. METHODS We retrospectively enrolled 480 patients with intermediate-stage HCC who underwent TACE at a tertiary care center between January 2008 and December 2019. Seven scores, which included the ALBI-TAE model, Bolondi's subclassification, HAP score, mHAP-II score, tumor burden score, six-and-twelve score, and seven-eleven criteria, were calculated and a head-to-head comparison was made in terms of prognostic power using Harrell's C-index. Prognostic factors associated with survival were analyzed. RESULTS ALBI-TAE group A had the longest median overall survival (OS) of 40.80 months, followed by ALBI-TAE groups B, C, and D of 20.14 months, 10.58 months, and 7.54 months, respectively, with significant differences (P < 0.001). Among the seven scores, the ALBI-TAE model had the best predictive performance (Harrell's C-index 0.633) in differentiating OS in intermediate-stage HCC patients. Moreover, the ALBI-TAE model was identified as an independent prognostic factor for survival outcome in multivariate analysis. CONCLUSION Our study confirmed the value of the ALBI-TAE model with excellent prognostic discriminatory power in intermediate-stage HCC patients. The ALBI-TAE model is a simple and valuable predictive tool to identify patients with good prognosis who can get the most benefit from TACE.
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Affiliation(s)
- Kittipitch Bannangkoon
- Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
| | - Keerati Hongsakul
- Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
| | - Teeravut Tubtawee
- Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand
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9
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Heinze C, Damm R, Othmer M, Thormann M, Surov A, Hass P, Seidesticker R, Seidensticker M, Ricke J, Powerski M, Pech M, Omari J. Local tumor control of intermediate and advanced stage hepatocellular carcinoma after local ablative treatment with image-guided interstitial high-dose-rate brachytherapy: A subgroup analysis of 286 HCC nodules. Brachytherapy 2023; 22:231-241. [PMID: 36697267 DOI: 10.1016/j.brachy.2022.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 11/08/2022] [Accepted: 11/25/2022] [Indexed: 01/24/2023]
Abstract
PURPOSE Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). RESULTS LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. CONCLUSIONS IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.
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Affiliation(s)
- Constanze Heinze
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany.
| | - Robert Damm
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Max Othmer
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Maximilian Thormann
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Alexey Surov
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Peter Hass
- Department of Radiotherapy, University Hospital Magdeburg, Magdeburg, Germany
| | | | - Max Seidensticker
- Department of Radiology, University Hospital Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital Munich, Munich, Germany
| | - Maciej Powerski
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Jazan Omari
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
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Pallerla SR, Hoan NX, Rachakonda S, Meyer CG, Van Tong H, Toan NL, Linh LTK, Giang DP, Kremsner PG, Bang MH, Song LH, Velavan TP. Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma. BMC Med Genomics 2022; 15:235. [PMID: 36345011 PMCID: PMC9641913 DOI: 10.1186/s12920-022-01386-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 10/14/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. MATERIALS AND METHODS We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2-∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. RESULTS Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. CONCLUSION The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes.
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Affiliation(s)
- Srinivas Reddy Pallerla
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany.
| | - Nghiem Xuan Hoan
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
- Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
| | - Sivaramakrishna Rachakonda
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany
| | - Christian G Meyer
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | | | | | - Le Thi Kieu Linh
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | - Dao Phuong Giang
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
- Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Peter G Kremsner
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany
- Centre de Recherches Medicales de Lambarene, Lambaréné, Gabon
| | - Mai Hong Bang
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
- Faculty of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Le Huu Song
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
- Department of Molecular Biology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam
| | - Thirumalaisamy P Velavan
- Institute of Tropical Medicine, Universitätsklinikum Tübingen, Universität Tübingen, Wilhelmstr 27, 72074, Tübingen, Germany
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
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Niu XK, He XF. A Nomogram Based on Preoperative Lipiodol Deposition after Sequential Retreatment with Transarterial Chemoembolization to Predict Prognoses for Intermediate-Stage Hepatocellular Carcinoma. J Pers Med 2022; 12:1375. [PMID: 36143160 PMCID: PMC9501090 DOI: 10.3390/jpm12091375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 12/24/2022] Open
Abstract
(1) Background: Conventional transarterial chemoembolization (cTACE) is the mainstay treatment for patients with Barcelona Clinic Liver Cancer (BCLC) B-stage hepatocellular carcinoma (HCC). However, BCLC B-stage patients treated with cTACE represent a prognostically heterogeneous population. We aim to develop and validate a lipiodol-deposition-based nomogram for predicting the long-term survival of BCLC B-stage HCC patients after sequential cTACE. (2) Methods: In this retrospective study, 229 intermediate-stage HCC patients from two hospitals were separately allocated to a training cohort (n = 142) and a validation cohort (n = 87); these patients underwent repeated TACE (≥4 TACE sessions) between May 2010 and May 2017. Lipiodol deposition was assessed by semiautomatic volumetric measurement with multidetector computed tomography (MDCT) before cTACE and was characterized by two ordinal levels: ≤50% (low) and >50% (high). A clinical lipiodol deposition nomogram was constructed based on independent risk factors identified by univariate and multivariate Cox regression analyses, and the optimal cutoff points were obtained. Prediction models were assessed by time-dependent receiver-operating characteristic curves, calibration curves, and decision curve analysis. (3) Results: The median number of TACE sessions was five (range, 4−7) in both cohorts. Before the TACE-3 sessions, the newly constructed nomogram based on lipiodol deposition achieved desirable diagnostic performance in the training and validation cohorts with AUCs of 0.72 (95% CI, 0.69−0.74) and 0.71 (95% CI, 0.68−0.73), respectively, and demonstrated higher predictive ability compared with previously published prognostic models (all p < 0.05). The prognostic nomogram obtained good clinical usefulness in predicting the patient outcomes after TACE. (4) Conclusions: Based on each pre-TACE lipiodol deposition, two sessions are recommended before abandoning cTACE or combining treatment for patients with intermediate-stage HCC. Furthermore, the nomogram based on pre-TACE-3 lipiodol deposition can be used to predict the prognoses of patients with BCLC B-stage HCC.
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Affiliation(s)
- Xiang-Ke Niu
- Department of Interventional Radiology, Affiliated Hospital of Chengdu University, Chengdu 610081, China
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Xiao-Feng He
- Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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12
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Kobayashi S, Fukushima T, Ueno M, Moriya S, Chuma M, Numata K, Tsuruya K, Hirose S, Kagawa T, Hattori N, Watanabe T, Matsunaga K, Suzuki M, Uojima H, Hidaka H, Kusano C, Suzuki M, Morimoto M. A prospective observational cohort study of lenvatinib as initial treatment in patients with BCLC-defined stage B hepatocellular carcinoma. BMC Cancer 2022; 22:517. [PMID: 35525913 PMCID: PMC9080183 DOI: 10.1186/s12885-022-09625-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 04/27/2022] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is the standard treatment for intermediate stage hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B). However, it often leads to a poor prognosis and decreased hepatic function especially in patients with BCLC substage B2. Lenvatinib (LEN) was demonstrated to be efficacious in these patients in the REFLECT phase 3 trial. We therefore aimed to evaluate the efficacy and safety of LEN as a first-line treatment for the patients with HCC at BCLC substage B2. METHODS This prospective observational study used LEN in TACE-naïve patients with HCC at BCLC substage B2 and preserved hepatic function. The primary endpoint was overall survival. A one-year survival rate threshold of 60% and an expected survival rate of 78%, based on previous reports of TACE, was assumed for setting the sample size. With a one-sided α-type error of 5% and 70% detection power, 25 patients were required over a 2-year enrollment period and 10-month follow-up period. RESULTS Thirty-one patients were enrolled in this study from June 2018 to June 2020. The 1-year survival rate was 71.0% (90% confidence interval, 68.4-73.6%). Median overall and progression-free survival periods were 17.0 and 10.4 months, and the objective response rates according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 and modified RECIST criteria were 22.6% and 70.0%, respectively. Common adverse events (AEs) were fatigue (68%), hypertension (65%), anorexia (61%), palmar-plantar erythrodysesthesia (39%), and thrombocytopenia (32%) of any grade; aspartate aminotransferase increased (23%), alanine aminotransferase increased (16%), and grade ≥ 3 proteinuria (13%). Treatment interruption and dose reduction were required in 61% and 81% of patients, respectively. LEN was discontinued in 29 patients due to disease progression (n = 17), AEs (n = 9), conversion to curative treatments (n = 2), and sudden death (n = 1), whereas post-LEN treatments were administered in 18 patients, including systemic chemotherapy (n = 11), TACE (n = 6), transarterial infusion (n = 1) and clinical trial (n = 1). CONCLUSIONS The results suggest that LEN provides treatment benefits as an initial therapeutic in patients with BCLC substage B2 HCC with a safety profile comparable to that previously reported.
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Affiliation(s)
- Satoshi Kobayashi
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan.
| | - Taito Fukushima
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Kota Tsuruya
- Department of Gastroenterology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Shunji Hirose
- Department of Gastroenterology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tatehiro Kagawa
- Department of Gastroenterology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Nobuhiro Hattori
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Kotaro Matsunaga
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Michihiro Suzuki
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Haruki Uojima
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Hisashi Hidaka
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Chika Kusano
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
| | - Motoko Suzuki
- Department of Data Science, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Manabu Morimoto
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Nakao 2-3-2, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan
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Deng J, Wen F. Transarterial Chemoembolization Combined With Tyrosine Kinase Inhibitors for Intermediate-Stage Hepatocellular Carcinoma, What Else Can We Do? Front Oncol 2022; 12:824799. [PMID: 35425716 PMCID: PMC9001928 DOI: 10.3389/fonc.2022.824799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 03/01/2022] [Indexed: 12/12/2022] Open
Abstract
Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, intermediate‐stage HCC is highly heterogeneous with a broad population with varying tumour burdens, liver function. This suggests that TACE monotherapy treatment might not be suitable for all patients with intermediate‐stage HCC. The administration of tyrosine kinase inhibitors (TKIs) has become an important treatment option for improving the prognosis of patients with advanced HCC. Over the years, several trials have been conducted to explore the effects of TACE combined with TKIs for intermediate-stage HCC. However, the clinical efficacy is still controversial, and its potential clinical utility needs to be confirmed. This review will focus on the recent progress of TACE combined TKIs for intermediate-stage HCC.
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Affiliation(s)
- Jun Deng
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Feng Wen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
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14
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Chi CT, Lee IC, Lee RC, Hung YW, Su CW, Hou MC, Chao Y, Huang YH. Effect of Transarterial Chemoembolization on ALBI Grade in Intermediate-Stage Hepatocellular Carcinoma: Criteria for Unsuitable Cases Selection. Cancers (Basel) 2021; 13:4325. [PMID: 34503135 PMCID: PMC8431519 DOI: 10.3390/cancers13174325] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/21/2021] [Accepted: 08/24/2021] [Indexed: 02/08/2023] Open
Abstract
Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). We aimed to identify unsuitable cases who were at risk of ALBI-grade migration by TACE. Consecutive 531 BCLC-B HCC patients undergoing TACE were reviewed, and factors associated with ALBI-grade migration were analyzed. There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Up-to-eleven (p = 0.007) performed better than up-to-seven (p = 0.146) to differentiate risk of dynamic ALBI score changes. Moreover, ALBI-grade migration to grade 3 has adverse effect on survival. In conclusion, tumor burden beyond up-to-eleven was associated with ALBI-grade migration after TACE, indicating that up-to-eleven can select TACE-unsuitable HCC patients who are at risk of liver function deterioration.
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Affiliation(s)
- Chen-Ta Chi
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
| | - I-Cheng Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Ya-Wen Hung
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (C.-T.C.); (I.-C.L.); (Y.-W.H.); (C.-W.S.); (M.-C.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
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Mocan T, Nenu I, Crăciun R, Spârchez Z. Treatment of hepatitis C virus infection in patients with hepatocellular carcinoma: Truth or dare? J Gastroenterol Hepatol 2021; 36:1518-1528. [PMID: 33326142 DOI: 10.1111/jgh.15376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 11/08/2020] [Accepted: 12/03/2020] [Indexed: 12/20/2022]
Abstract
The discovery of direct acting antivirals (DAA) with high rates of sustained virusological response is the biggest epoch-making event in the history of hepatitis C virus (HCV) treatment. DAAs improve liver function, prevent hepatic decompensation, and might even reverse liver fibrosis. Although initial research pointed towards a potential drawback, it is now known beyond doubt that DAA treatment reduces hepatocellular carcinoma (HCC) occurrence or recurrence after curative treatments. Unfortunately, the story has reached another plot twist, as several other issues have emerged: (i) Should we treat patients with early HCC and HCV before or after surgery/ablation? (ii) Should patients with HCC on the waiting list receive DAA before or after liver transplantation? (iii) Should we use interferon-free in patients with intermediate stage HCC or in patients under systemic treatments? In this review, we aim to offer some evidence-based answers to these changing clinical dilemmas where possible, or at least some educated guesses in cases were no or little data exists.
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Affiliation(s)
- Tudor Mocan
- 3rd Medical Department, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Institute for Gastroenterology and Hepatology "Prof. Dr. O. Fodor", Cluj-Napoca, Romania
| | - Iuliana Nenu
- 3rd Medical Department, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Institute for Gastroenterology and Hepatology "Prof. Dr. O. Fodor", Cluj-Napoca, Romania
| | - Rareș Crăciun
- 3rd Medical Department, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Institute for Gastroenterology and Hepatology "Prof. Dr. O. Fodor", Cluj-Napoca, Romania
| | - Zeno Spârchez
- 3rd Medical Department, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Institute for Gastroenterology and Hepatology "Prof. Dr. O. Fodor", Cluj-Napoca, Romania
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Campigotto M, Giuffrè M, Colombo A, Visintin A, Aversano A, Budel M, Masutti F, Abazia C, Crocé LS. Comparison between hepatocellular carcinoma prognostic scores: A 10-year single-center experience and brief review of the current literature. World J Hepatol 2020; 12:1239-1257. [PMID: 33442451 PMCID: PMC7772726 DOI: 10.4254/wjh.v12.i12.1239] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/14/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) represents the most common primitive liver malignancy. A relevant concern involves the lack of agreement on staging systems, prognostic scores, and treatment allocation algorithms. AIM To compare the survival rates among already developed prognostic scores. METHODS We retrospectively evaluated 140 patients with HCC diagnosed between February 2006 and November 2017. Patients were categorized according to 15 prognostic scoring systems and estimated median survivals were compared with those available from the current medical literature. RESULTS The median overall survival of the cohort of patients was 35 (17; 67) mo, and it was statistically different in relation to treatment choice, ultrasound surveillance, and serum alpha-fetoprotein. The Italian Liver Cancer (ITA.LI.CA) tumor staging system performed best in predicting survival according to stage allocation among all 15 evaluated prognostic scores. Using the ITA.LI.CA prognostic system, 28.6%, 40.7%, 22.1%, and 8.6% of patients fell within stages 0-1, 2-3, 4-5 and > 5 respectively. The median survival was 57.9 mo for stages 0-1, 43 mo for stages 2-3, 21.7 mo for stages 4-5, and 10.4 mo for stage > 5. The 1-, 3-, and 5-year survival rates were respectively 95%, 65%, and 20%, for stages 0-1; 94.7%, 43.9% and 26.3% for stages 2-3; 71%, 25.8% and 16.1% for stages 4-5; and 50%, 16.7% and 8.3% for stage > 5. At the same time, although statistically significant in prognostic stratification, the most commonly used Barcelona Clinic Liver Cancer system showed one of the most relevant differences in median survival, especially for stages A and C, when compared to the medical literature. In fact, 10.7%, 59.3%, 27.1%, 1.4%, and 0% of patients were stratified into stages 0, A, B, C, and D respectively. The median survival was > 81.1 mo for stage 0, 44.9 mo for stage A, 21.3 mo for stage B, and 3.1 mo for stage C. The 1-, 3-, and 5-year survival rates were respectively 86.7%, 60%, and 46.7% for stage 0; 91.6%, 50.6%, and 20.5% for stage A; 73.7%, 23.7% and 13.2% for stage B; and 2%, 0% and 0% for stage C. CONCLUSION Survival analysis shows excellent prognostic ability of the ITA.LI.CA scoring system compared to other staging systems.
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Affiliation(s)
- Michele Campigotto
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Mauro Giuffrè
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy.
| | - Anna Colombo
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Alessia Visintin
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Alessandro Aversano
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Martina Budel
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
| | - Flora Masutti
- Clinica Patologie del Fegato, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste 34149, Italy
| | - Cristiana Abazia
- Clinica Patologie del Fegato, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste 34149, Italy
| | - Lory Saveria Crocé
- Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e Della Salute, Università degli Studi di Trieste, Trieste 34149, Italy
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Prince D, Liu K, Xu W, Chen M, Sun JY, Lu XJ, Ji J. Management of patients with intermediate stage hepatocellular carcinoma. Ther Adv Med Oncol 2020; 12:1758835920970840. [PMID: 33224278 PMCID: PMC7649909 DOI: 10.1177/1758835920970840] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 10/08/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.
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Affiliation(s)
- David Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Liver Injury and Cancer Program, The Centenary Institute, Sydney, NSW, Australia
| | - Weiqi Xu
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Jin-Yu Sun
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Sparkfire Scientific Research Group, Nanjing Medical University, Nanjing, China
| | - Xiao-Jie Lu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui 323000, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, 323000, China
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Yoo JJ, Yu SJ, Lee B, Cho EJ, Lee JH, Kim SG, Kim YJ, Kim YS, Yoon JH. Appraisal of a Model to Estimate Survival in Ambulatory Patients with Hepatocellular Carcinoma Classified as Barcelona Clinic Liver Cancer Stage B. Gut Liver 2020; 14:377-386. [PMID: 31533399 PMCID: PMC7234889 DOI: 10.5009/gnl19112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/11/2019] [Accepted: 05/23/2019] [Indexed: 12/28/2022] Open
Abstract
Background/Aims Patients with an intermediate stage of hepatocellular carcinoma (HCC) represent a highly heterogeneous population; therefore, many models have been proposed to predict the survival of these patients. The aim of this study was to evaluate the prognostic performance of a novel subclassification for tumors classified as Barcelona Clinic Liver Cancer (BCLC) stage B using the Model to Estimate Survival in Ambulatory HCC patients (MESIAH). Methods This analysis was based on 377 patients with HCC treated at Seoul National University Hospital (training cohort) and 189 patients at the Soonchunhyang University Bucheon Hospital (validation cohort). Four subclassification systems were tested: MESIAH; original BCLC B subclassification (B1, B2, B3, and B4); modified model A (B1, B2, and B3+B4); and modified model B (B1, B2+B3, and B4). Results Median survival progressively decreased from stage B1 through stages B2 to B3 according to the new MESIAH subclassification (p<0.001). Moreover, significantly different survival among contiguous stages was observed. In the multivariable Cox regression, the MESIAH subclassification was an independent predictor of overall survival (p<0.001). In terms of discrimination and calibration, MESIAH performed better than the original BCLC B subclassification, modified model A and modified model B. Conclusions The MESIAH model would be an effective tool for stratifying heterogeneous BCLC stage B cancer, and the ability of this model to predict survival is better than that of the other previously proposed models.
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Affiliation(s)
- Jeong-Ju Yoo
- Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Bora Lee
- Department of Statistics, Graduate School, Chung-Ang University, Seoul, Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Liu YW, Lin CC, Yong CC, Wang CC, Chen CL, Wang JH, Yen YH. Prognosis after resection of single large hepatocellular carcinoma: Results from an Asian high-volume liver surgery center. PLoS One 2020; 15:e0230897. [PMID: 32218593 PMCID: PMC7100934 DOI: 10.1371/journal.pone.0230897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/11/2020] [Indexed: 02/08/2023] Open
Abstract
Background & aims In 2012, the Barcelona Clinic Liver Cancer (BCLC) system designated a single large hepatocellular carcinoma (SLHCC) (>5 cm) as BCLC stage A rather than stage B. However, a recent study from western countries reported that prognosis following liver resection (LR) among patients with SLHCC was similar to that among patients with BCLC stage B. We aim to evaluate the prognosis following LR among patients with SLHCC from an Asian high-volume liver surgery center. Methods Patients who underwent curative-intent LR for histologically proven HCC between 2011 and 2017 were enrolled using an HCC registry database. Overall survival (OS) among patients with BCLC stages 0, A, and B was examined. Patients with a SLHCC were classified as BCLC stage A1. Results Among 543 patients, 89 (16.4%) were BCLC stage 0, 289 (53.2%) were BCLC stage A, 92 (16.9%) were BCLC stage A1, and 73 (13.4%) were BCLC stage B. The median follow-up was 38 months. The five-year OS rates among patients with BCLC stages 0, A, A1, and B were 83.5%, 83.7%, 77.4%, and 55.4%, respectively (p<0.001). No difference in OS was noted for patients with BCLC stage A versus A1 (p = 0.11), even after adjusting for competing factors (hazard ratio = 0.97, 95% confidence interval = 0.53–1.79; p = 0.93). Conclusion Prognosis following LR among patients with SLHCC was similar to that among patients with BCLC stage A. The prognosis for SLHCC should thus be considered comparable to that for BCLC stage A.
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Affiliation(s)
- Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
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20
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Cho HJ, Kim SS, Kang SY, Yang MJ, Noh CK, Hwang JC, Lim SG, Shin SJ, Lee KM, Yoo BM, Lee KJ, Kim JH, Cho SW, Cheong JY. A Proposal for Modification of the Barcelona Clinic Liver Cancer Staging System Considering the Prognostic Implication of Performance Status. Gut Liver 2020; 13:557-568. [PMID: 31023007 PMCID: PMC6743810 DOI: 10.5009/gnl18444] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 11/19/2018] [Accepted: 12/13/2018] [Indexed: 12/16/2022] Open
Abstract
Background/Aims Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1-2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. Methods A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. Results As a result, the BCLC C stage, which includes patients with PS 1-2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p<0.001). Conclusions An accurate and relevant staging system for patients with HCC was derived though modification of the BCLC system based on PS.
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Affiliation(s)
- Hyo Jung Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Soon Sun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - So Young Kang
- Office of Biostatistics, Ajou University School of Medicine, Suwon, Korea
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Choong Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Chul Hwang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sun Gyo Lim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Jae Shin
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Kee Myung Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Byung Moo Yoo
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jin Hong Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Sung Won Cho
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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BCLC-B Subclassification and the Hong Kong Liver Cancer System in Intermediate Hepatocellular Carcinoma: Identifying Candidates for Curative Therapy. Am J Clin Oncol 2020; 42:466-471. [PMID: 30913090 DOI: 10.1097/coc.0000000000000539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION The intermediate stage of the Barcelona Clinic Liver Cancer (BCLC) classification includes a heterogenous population of patients with hepatocellular carcinoma (HCC), and palliative treatment with transarterial chemoembolization is recommended for all of them. In this regard, 2 other classifications could be useful, the subclassification BCLC-B (SUB) and the classification Hong Kong Liver Cancer (HKLC). OBJECTIVE To determine the indication of curative or palliative treatment between SUB and HKLC in BCLC-B patients. PATIENTS AND METHODS A retrospective study in HCC patients seen between 2011 and 2016 in southern Brazil. Demographic, clinical, and laboratory data were collected. HCC staging was performed with BCLC, SUB, and HKLC. RESULTS A total of 570 patients with HCC were assessed, of whom 95 were classified as BCLC-B: 25 (26.0%) B1, 48 (50.5%) B2, 9 (9.5%) B3, and 13 (13.7%) B4. Overall median survival was 21.1 (95% confidence interval, 14.2-28.0) months. Median survival was higher for BCLC-B1 patients than in subgroups B3 (P=0.046) and B4 (P=0.001), and this was also seen for B2 versus B4 (P=0.044). Regarding the HKLC classification, a significantly higher median survival was observed for HKLC-I and HKLC-IIB in relation to the categories HKLC-IIIA (P<0.001 and 0.004, respectively) and HKLC-IIIB (P<0.001 and 0.006, respectively). When HKLC was applied, the following were identified as candidates for curative treatment: BCLC-B1, 24 (96.0%); BCLC-B2, 26 (54.2%); BCLC-B3, 0 (0%); and BCLC-B4, 3 (23.1%). CONCLUSION In intermediate HCC, SUB was able to identify a subset of patients with a higher overall survival. According to HKLC, 55.8% of BCLC-B patients could receive curative treatment.
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Tian Y, Lyu H, He Y, Kanduri HK. Evaluating the Ability of the New Subclassification to Prognosticate Outcomes Following Hepatectomy for Patients with HBV-Related HCC. J Gastrointest Cancer 2020; 50:400-407. [PMID: 29512001 DOI: 10.1007/s12029-018-0085-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recently, experts proposed subclassification for BCLC B patients. In this study, we aimed to evaluate the efficient of subclassification of patients with hepatitis B virus-related hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) staging system. METHODS Seven hundred twenty-nine consecutive hepatitis B virus-related HCC patients with BCLC stage B classification who underwent hepatectomy in the period 2006-2012 were retrospectively analyzed. Patients were reclassified based on the new proposed subclassification of the BCLC B stage from B1 to B4. The prognosis of subclassification was tested using Kaplan-Meier statistics analysis. RESULTS There were 145 (19.9%), 480 (65.8%), 62 (8.5%), and 42 (5.8%) patients in B1, B2, B3, and B4, respectively. The result suggested that overall and tumor-free survival rates among the B1, B2, and B3 subclassification in the Bolondi system had significant difference (P < 0.05). However, no significant difference was found between B3 and B4 subclassifications. Cox regression showed that BCLC B subclassification, largest/smallest diameter, and anatomic liver resection were independent predictors of tumor-free survival. BCLC B subclassification and anatomic liver resection were independent predictors of overall survival. CONCLUSIONS The subclassification of BCLC stage B can be used in patients with HBV-related HCC who underwent curative intent hepatectomy. Patients in BCLC B1 and B2 subgroups should be treated more aggressively than patients in B3 and B4 subgroups. B3 and B4 groups should be merged for patients with HBV-related HCC who underwent curative intent hepatectomy.
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Affiliation(s)
- Yunhong Tian
- The Third Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu, China. .,Department of General Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, 215006, China.
| | - Huan Lyu
- Department of General Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, 215006, China
| | - Yunhong He
- Department of General Surgery, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong, Sichuan, 215006, China
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Giannini EG, Bodini G, Furnari M, Marabotto E. Hepatocellular Carcinoma Intermediate Stage Subclassification Systems: One, None, and One Hundred Thousand. Liver Cancer 2019; 8:524-526. [PMID: 31799210 PMCID: PMC6883457 DOI: 10.1159/000501485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 06/12/2019] [Indexed: 02/04/2023] Open
Affiliation(s)
- Edoardo G. Giannini
- *Edoardo G. Giannini, MD, PhD, F.A.C.G., F-FIRE, Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, No.6, IT–16132 Genoa (Italy), E-Mail
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Hu KS, Tang B, Yuan J, Lu SX, Li M, Chen RX, Zhang L, Ren ZG, Yin X. A new substage classification strategy for Barcelona Clinic Liver Cancer stage B patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2019; 34:1984-1991. [PMID: 30932246 DOI: 10.1111/jgh.14673] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 03/03/2019] [Accepted: 03/24/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM Patients with Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma are a heterogeneous population, and the classifications available could not predict the prognosis accurately. Herein, we proposed a new substage classification method, Scoring Method for Intermediate Stage, for precise classification and clinical guidance in hepatocellular carcinoma patients within Barcelona Clinic Liver Cancer stage B. METHODS A total of 1026 stage B patients of hepatocellular carcinoma who underwent transcatheter arterial chemoembolization as a first-line treatment in Liver Cancer Institute, Zhongshan Hospital, Fudan University were retrospectively enrolled. The prognostic evaluation ability of the new substage classification criteria was analyzed, in comparison with the existing substage classification criteria. RESULTS Using Scoring Method for Intermediate Stage, 1026 stage B patients were subclassified into three subgroups, based on Child-Pugh score and up-to-7 grade, as B1 (scoring 2), B2 (scoring 3 or 4), and B3 (scoring 5 or 6). The median survival time of the three substages was 29 (95% confidence interval [CI]: 25-36), 19 (95% CI: 16-21), and 10 (95% CI: 8-12) months, respectively. More favorable discrimination efficacy was identified by the new criteria in comparison with the existing substage classification criteria, including Bolondi, Kinki, MICAN, and Kim's criteria. Moreover, multivariate analyses indicated that the novel classification was highly associated with prognosis (Hazard ratio(s) = 1.63, 95% CI: 1.43-1.86, P < 0.001). CONCLUSIONS Scoring Method for Intermediate Stage demonstrates satisfying capacity in classifying patients with stage B hepatocellular carcinoma and predicting prognosis.
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Affiliation(s)
- Ke-Shu Hu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Bei Tang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Jia Yuan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Shen-Xin Lu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Miao Li
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Rong-Xin Chen
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Lan Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Zheng-Gang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Xin Yin
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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25
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Golfieri R, Bargellini I, Spreafico C, Trevisani F. Patients with Barcelona Clinic Liver Cancer Stages B and C Hepatocellular Carcinoma: Time for a Subclassification. Liver Cancer 2019; 8:78-91. [PMID: 31019899 PMCID: PMC6465743 DOI: 10.1159/000489791] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 04/27/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) intermediate and advanced stages (BCLC B and C) of hepatocellular carcinoma (HCC) both include heterogeneous populations. Patients classified as BCLC stage B present with different tumour burdens, and the recommended treatment is transarterial chemoembolization (TACE). A similar heterogeneity of tumour burden and liver function can be found among patients classified as BCLC stage C, which includes diverse clinical features (performance status [PS] 1-2), macrovascular invasion (MVI) including portal vein tumour (PVT) thrombosis, and/or extra-hepatic spread. Nonetheless, the anti-tumoural treatment formally recommended by Western guidelines is systemic therapy with sorafenib. SUMMARY Several proposals of subclassification for both these stages have been suggested in recent years, differentiating the more appropriate treatments for each substage. In particular, for BCLC stage C patients with PVT, therapeutic indications, clinical outcomes, and response to locoregional therapy are notably different in the presence of subsegmental, segmental or main PVT. Accordingly, liver resection and transarterial therapies, such as TACE or transarterial embolization (TAE) and 90Y-radioembolization (TARE), can be performed in locally advanced HCC with intrahepatic MVI according to its extent. In fact, surgery and TACE/TAE/TARE have no contraindications in the presence of PVT limited to the subsegmental or segmental branches in Child-Pugh class A patients, whereas only TARE should be utilized when there is lobar branch involvement. The presence of PS 1 should not be sufficient to allocate patients to the advanced stage since this would preclude any potential treatment for HCC. Patients should be properly classified as BCLC C only in cases of main portal trunk PVT, and treated according to the guidelines, provided that they belong to Child-Pugh class A. KEY MESSAGES Subclassifications of BCLC B and C stages are urgently needed and require validation in order to guide clinicians towards the most effective treatment option.
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Affiliation(s)
- Rita Golfieri
- Radiology Unit, Department of Diagnostic and Preventive Medicine, S. Orsola-Malpighi Hospital, Alma Mater Studiorum – University of Bologna, Bologna, Italy
| | - Irene Bargellini
- Interventional Radiology Unit, Pisa University Hospital, Pisa, Italy
| | - Carlo Spreafico
- Interventional Radiology Unit, Department of Radiology, Istituto Tumori of Milan IRCCS Foundation, Milan, Italy
| | - Franco Trevisani
- Division of Semeiotics, Department of Medical and Surgical Sciences, Alma Mater Studiorum, Bologna, Italy
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26
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Ikeda K. Recent advances in medical management of hepatocellular carcinoma. Hepatol Res 2019; 49:14-32. [PMID: 30308081 DOI: 10.1111/hepr.13259] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/20/2018] [Accepted: 10/02/2018] [Indexed: 12/18/2022]
Abstract
Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon-occluded TACE is an effective therapy for localized HCC and drug-eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. Other molecular-targeted and immune-oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of molecular-targeted therapy for TACE-resistant HCC in the intermediate stage.
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Affiliation(s)
- Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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27
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Cappelli A, Sangro P, Mosconi C, Deppe I, Terzi E, Bilbao JI, Rodriguez-Fraile M, De Benedittis C, Ricke J, Golfieri R, Sangro B. Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage. Eur J Nucl Med Mol Imaging 2018; 46:661-668. [PMID: 30209522 DOI: 10.1007/s00259-018-4152-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Accepted: 08/28/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B according to the Barcelona Clinic Liver Cancer classification) are a heterogeneous group with different degrees of liver function impairment and tumour burden. The recommended treatment is transarterial chemoembolization (TACE). However, patients in this group may be judged as poor candidates for TACE because the risk-benefit ratio is low. Such patients may receive transarterial radioembolization (TARE) only by entering a clinical trial. Experts have proposed that the stage could be further divided into four substages based on available evidence of treatment benefit. We report here, for the first time, the outcome in patients with BCLC-B2 substage HCC treated with TARE. METHODS A retrospective analysis of the survival of 126 patients with BCLC-B2 substage HCC treated with TARE in three European hospitals was performed. RESULTS Overall median survival in patients with BCLC-B2 substage was not significantly different in relation to tumour characteristics; 19.35 months (95% CI 8.27-30.42 months) in patients with a single large (>7 cm) HCC, and 18.43 months (95% CI 15.08-21.77 months) in patients with multinodular HCC (p = 0.27). However, there was a higher proportion of long-term survivors at 36 months among those with a single large tumour (29%) than among those with multiple tumours (16.8%). CONCLUSION Given the poor efficacy of TACE in treating patients with BCLC-B2 substage HCC, TARE treatment could be a better choice, especially in those with a large tumour.
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Affiliation(s)
- Alberta Cappelli
- Radiology Unit, Department of Diagnostic and Preventive Medicine, University of Bologna, Policlinico di S.Orsola, Via Albertoni 15, 40138, Bologna, Italy
| | - Paloma Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain
| | - Cristina Mosconi
- Radiology Unit, Department of Diagnostic and Preventive Medicine, University of Bologna, Policlinico di S.Orsola, Via Albertoni 15, 40138, Bologna, Italy
| | - Iris Deppe
- Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain
| | - Eleonora Terzi
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Policlinico di S.Orsola, Bologna, Italy
| | - Jose I Bilbao
- Interventional Radiology, Clinica Universidad de Navarra-IDISNA, Pamplona, Spain
| | | | - Caterina De Benedittis
- Radiology Unit, Department of Diagnostic and Preventive Medicine, University of Bologna, Policlinico di S.Orsola, Via Albertoni 15, 40138, Bologna, Italy
| | - Jens Ricke
- Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic and Preventive Medicine, University of Bologna, Policlinico di S.Orsola, Via Albertoni 15, 40138, Bologna, Italy.
| | - Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Avda. Pio XII 36, 31008, Pamplona, Spain.
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Long-term survival after partial hepatectomy for sub-stage patients with intermediate stage hepatocellular carcinoma. Int J Surg 2018; 56:256-263. [PMID: 29935368 DOI: 10.1016/j.ijsu.2018.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 04/12/2018] [Accepted: 06/14/2018] [Indexed: 02/06/2023]
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29
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Yasui Y, Tsuchiya K, Kurosaki M, Takeguchi T, Takeguchi Y, Okada M, Wang W, Kubota Y, Goto T, Komiyama Y, Higuchi M, Takaura K, Hayashi T, Takada H, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Enomoto N, Himeno Y, Izumi N. Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization. Hepatol Res 2018; 48:442-450. [PMID: 29278654 DOI: 10.1111/hepr.13048] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 12/20/2017] [Accepted: 12/21/2017] [Indexed: 12/18/2022]
Abstract
AIM Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. METHODS We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. RESULTS The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). CONCLUSIONS The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.
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Affiliation(s)
- Yutaka Yasui
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Takaya Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuko Takeguchi
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Mao Okada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Wan Wang
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yohei Kubota
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tomoyuki Goto
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasuyuki Komiyama
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Mayu Higuchi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kenta Takaura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tsuguru Hayashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Hitomi Takada
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Nobuharu Tamaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Jun Itakura
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yuka Takahashi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasuhiro Asahina
- Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yoshiro Himeno
- Department of Radiology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
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30
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Transcatheter Arterial Chemoembolization With or Without Radiofrequency Ablation: Outcomes in Patients With Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma. AJR Am J Roentgenol 2018; 210:891-898. [PMID: 29412017 DOI: 10.2214/ajr.17.18177] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVE The objective of our study was to clarify the indications for transcatheter arterial chemoembolization (TACE) of the hepatic artery combined with radiofrequency ablation (RFA), which we refer to as "TACE-RFA," for patients with hepatocellular carcinoma (HCC) beyond the Milan criteria. This study assessed the prognoses of patients with intermediate-stage HCC, which we defined as Barcelona Clinic Liver Cancer (BCLC) stage B (hereafter referred to as BCLC-B), according to the BCLC-B substages through treatment in a multicenter study. MATERIALS AND METHODS Two-hundred thirty patients with intermediate-stage HCC who were treated from January 2000 to December 2015 were enrolled. These patients were divided into four classes (B1-B4) according to the Bolondi classification. Between these substages, the prognosis of patients who underwent TACE-RFA was compared with that of patients who underwent TACE, the latter of which is the suggested standard therapy for patients with BCLC-B HCC. RESULTS TACE-RFA and hepatic resection survival curves were better than those of TACE (p < 0.001 for TACE-RFA vs TACE). In particular, for substages B1 and B2, the overall survival rates of patients who underwent TACE-RFA were significantly higher than those who underwent TACE (B1, p < 0.001 for TACE-RFA vs TACE; B2, p = 0.015 for TACE-RFA vs TACE). CONCLUSION The indications for TACE-RFA may be expanding to BCLC-B HCC. For patients with disease classified as substages B1 and B2, TACE-RFA may be a better treatment modality than TACE alone.
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31
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Biolato M, Gallusi G, Iavarone M, Cabibbo G, Racco S, De Santis A, Corte CD, Maida M, Attili AF, Sangiovanni A, Cammà C, La Torre G, Gasbarrini A, Grieco A. Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Ann Hepatol 2018; 17:110-118. [PMID: 29311396 DOI: 10.5604/01.3001.0010.7542] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal. PATIENTS AND METHODS This is a retrospective multicenter cohort study including patients with intermediate HCC treated with transarterial chemoembolization (TACE). Predictors of survival were identified using the Cox proportional regression model. RESULTS 289 Barcelona Clinic Liver Cancer (BCLC) B patients were included. Median overall survival of the whole cohort was 23 months (C.I. 95% 20.2- 25.8). Child A status (H.R. 1.35, C.I. 95% 1.02-1.78) and tumour burden beyond the up-to-seven criterion (H.R. 1.39, C.I. 95% 1.07- 1.80) were independent prognostic factors for overall survival on multivariate analysis. Analysis of the substages showed that median survival was 33.0 months for B1 stage (n = 81), 20.8 months for B2 stage (n = 106), 16.1 months for B3 stage (n = 24), 22.2 months for B4 stage (n = 42) and 15.0 months for quasi-C stage (n = 36). Regarding the discriminatory ability of the substaging proposal, the log rank test showed a significant survival difference for B1vs. B4 (p = 0.003) and B1 vs. Quasi-C (p = 0.039) and a trend for B1 vs. B2 (p = 0.05) and B1 vs. B3 (p = 0.05). CONCLUSIONS Apart from substage B1, BCLC-B subclassification does not discriminate perfectly patients treated with TACE. Also some patients in substage B4 can benefit from TACE.
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Affiliation(s)
- Marco Biolato
- Department of Internal Medicine, Fondazione Policlinico Gemelli Catholic University of the Sacred Heart, Rome, Italy
| | - Giulia Gallusi
- Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Massimo Iavarone
- UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Simona Racco
- Department of Internal Medicine, Fondazione Policlinico Gemelli Catholic University of the Sacred Heart, Rome, Italy
| | - Adriano De Santis
- Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Cristina Della Corte
- UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Marcello Maida
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Adolfo Francesco Attili
- Division of Gastroenterology, Department of Clinical Medicine, La Sapienza University of Rome, Rome, Italy
| | - Angelo Sangiovanni
- UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Calogero Cammà
- Section of Gastroenterology, DIBIMIS, University of Palermo, Palermo, Italy
| | - Giuseppe La Torre
- Department of Public Health and Infectious Diseases, Sapienza University, Rome, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Fondazione Policlinico Gemelli Catholic University of the Sacred Heart, Rome, Italy
| | - Antonio Grieco
- Department of Internal Medicine, Fondazione Policlinico Gemelli Catholic University of the Sacred Heart, Rome, Italy
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32
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Kim JH, Shim JH, Lee HC, Sung KB, Ko HK, Ko GY, Gwon DI, Kim JW, Lim YS, Park SH. New intermediate-stage subclassification for patients with hepatocellular carcinoma treated with transarterial chemoembolization. Liver Int 2017; 37:1861-1868. [PMID: 28581250 DOI: 10.1111/liv.13487] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 05/30/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIM The need for a subclassification of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage (BCLC B) has arisen because of its diversity. We evaluated the prognostic capability of the BCLC B subclassification proposed by Bolondi et al. in patients treated with transarterial chemoembolization (TACE). Furthermore, we introduce a new subclassification for intermediate-stage hepatocellular carcinoma (HCC) by using a new parameter related to tumour burden (up-to-11 criteria). METHODS Of 3268 patients treated with TACE as first-line treatment, 821 patients with intermediate-stage HCC were included in this study. RESULTS According to the Bolondi subclassification, 208 (25.3%), 529 (64.5%), 43 (5.2%) and 41 (5%) patients were in B1, B2, B3 and B4 respectively. The B1, B2 and B3 subclasses in the Bolondi system showed significantly different survival between contiguous stages with median survival of 51.5, 26 and 14.8 months, respectively (both P<.001 for B1 vs B2 and B2 vs B3); however, survival was rather worse in B3 than B4 (14.8 vs 25 months, P=.025). According to the newly proposed subclassification, 410 (50%), 364 (44.3%) and 47 (5.7%) patients were in B1, B2 and B3 respectively. The median survival progressively decreased from B1 (44.8 months) to B2 (21.5 months) and B3 (11.3 months), with a significant difference between contiguous stages (both P<.001 for B1 vs B2 and B2 vs B3). CONCLUSIONS Our new BCLC B substaging system, with up-to-11 criteria and Child-Pugh class as main parameters, has excellent discriminatory power to subclassify TACE-treated patients into three prognostic substages.
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Affiliation(s)
- Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Kyu-Bo Sung
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Heung-Kyu Ko
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Jong Woo Kim
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul, Korea
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Pinato DJ, Howell J, Ramaswami R, Sharma R. Review article: delivering precision oncology in intermediate-stage liver cancer. Aliment Pharmacol Ther 2017; 45:1514-1523. [PMID: 28440552 DOI: 10.1111/apt.14066] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 03/03/2017] [Accepted: 03/06/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Intermediate-stage hepatocellular carcinoma (HCC), for which trans-arterial chemoembolization (TACE) constitutes the standard of care, is a patient subgroup with significant heterogeneity in clinical outcome. Sources of variation relate to differences in tumour burden, hepatic reserve, ethnicity and treatment modalities. Increasing research efforts have been dedicated to minimise the clinical diversity of this patient population and enhance optimal provision of treatment. AIM To comprehensively review the diverse prognostic models that have been proposed to refine the prognostic prediction of patients with HCC undergoing TACE. RESULTS A number of prognostic algorithms (HAP, ART, ABCR score and many others) have shown potential to address the clinical heterogeneity characterising patients with intermediate-stage HCC and facilitate early identification of patients with poor prognostic features in whom alternative treatments or best supportive care might be more appropriate than TACE. CONCLUSIONS While an improved characterisation of intermediate-stage HCC is a highly important clinical aim, current evidence suggests that novel prognostic algorithms in this patient population may offer potential benefits but non-negligible challenges in the provision of TACE. This review summarises the currently available evidence to facilitate the development of precision oncology in intermediate-stage HCC.
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Affiliation(s)
- D J Pinato
- Division of Surgery and Cancer, Hammersmith Campus of Imperial College London, London, UK
| | - J Howell
- Division of Surgery and Cancer, Hammersmith Campus of Imperial College London, London, UK.,Centre for Population Health, MacFarlane-Burnet Institute, Melbourne, VIC, Australia.,Department of Medicine, Royal Melbourne Hospital and St Vincent's Hospital, Melbourne, VIC, Australia.,University of Melbourne, Melbourne, VIC, Australia
| | - R Ramaswami
- Division of Surgery and Cancer, Hammersmith Campus of Imperial College London, London, UK
| | - R Sharma
- Division of Surgery and Cancer, Hammersmith Campus of Imperial College London, London, UK
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34
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Xu Y, Shen Q, Liu P, Xu Z, Wu P, Lu Z, Chen Y, Huang B, Qian G. Microwave ablation for the treatment of hepatocellular carcinoma that met up-to-seven criteria: feasibility, local efficacy and long-term outcomes. Eur Radiol 2017; 27:3877-3887. [PMID: 28188425 DOI: 10.1007/s00330-017-4740-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Revised: 12/24/2016] [Accepted: 01/03/2017] [Indexed: 12/15/2022]
Abstract
OBJECTIVES This study aimed to evaluate the feasibility, local efficacy and long-term outcomes of microwave (MW) ablation for the treatment of hepatocellular carcinoma (HCC) that met up-to-seven criteria. METHODS Between January 2007 and January 2012, 142 HCC patients with 294 nodules, which conformed to up-to-seven criteria, were enrolled into this retrospective study. All patients were followed up for more than 3 years after receiving MW ablation. Technical success, complications, local tumour progression (LTP) and distant recurrence (DR) were monitored. Recurrence-free survival (RFS), overall survival (OS) and prognostic factors were analysed. RESULTS Primary technical efficacy was achieved in 95.2% (280/294) of the carcinomatous nodules, and major complications occurred in four (2.8%) patients. Among the 294 tumours, LTP was observed in 44 (15.0%) tumours. Among the 142 patients, DR was observed in 97 (68.3%) patients. The estimated OS rates after MW ablation at 1, 3 and 5 years were 97.2%, 75.4% and 50.6%, respectively; and the corresponding RFS rates were 76.1%, 33.1% and 19.5%, respectively. CONCLUSIONS MW ablation is a safe and effective treatment with a high rate of primary technical efficacy for patients with HCC that met up-to-seven criteria. KEY POINTS • The first study expanding MW ablation to HCC category beyond Milan criteria. • The first report that used up-to-seven criteria as indications for MW ablation. • HCC of up-to-seven criteria viewed as a subgroup of BCLC stage B. • MW ablation is safe and effective for treating HCC within up-to-seven criteria. • MW ablation is preferable in treating unresectable HCC within up-to-seven criteria.
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Affiliation(s)
- Yun Xu
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Qiang Shen
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Pei Liu
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Zhongqi Xu
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Panpan Wu
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Zhenghua Lu
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Yi Chen
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Bin Huang
- Department of radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China
| | - Guojun Qian
- Department of minimal invasion therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University of Chinese PLA, 225 Changhai Rd, Shanghai, 200438, China.
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Dasse KD, Lander MJ, Novelli PM. Chemoembolization With Drug-Eluting Beads for the Treatment of Hepatocellular Carcinoma. J Adv Pract Oncol 2016; 7:764-778. [PMID: 29670812 PMCID: PMC5902156 DOI: 10.6004/jadpro.2016.7.7.8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Kathy Diener Dasse
- Department of Pharmacy Services, University of Michigan Health Systems, Ann Arbor, Michigan
| | - Michael J Lander
- Pharmacy Services, Mayo Clinic - St. Mary's Hospital, Rochester, Minnesota
| | - Paula M Novelli
- Division of Vascular and Interventional Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Subclassification of patients with intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinoma using the up-to-seven criteria and serum tumor markers. Hepatol Int 2016; 11:105-114. [PMID: 27766479 DOI: 10.1007/s12072-016-9771-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Accepted: 10/03/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intermediate-stage [Barcelona Clinic Liver Cancer stage-B (BCLC-B)] hepatocellular carcinoma (HCC) comprises of a heterogeneous population of patients with a wide range of tumor burdens. We therefore formulated a subclassification of BCLC-B HCC using the up-to-seven criteria and tumor markers according to the results of a retrospective analysis of these patients. METHODS This study included 125 patients newly diagnosed with BCLC-B HCC who underwent transarterial chemoembolization. Among them, 39 and 86 were within or beyond the up-to-seven criteria, respectively. Multivariate Cox proportional hazards analysis was performed to investigate factors that contributed to better prognosis associated with the criteria. RESULTS Cumulative overall survival (OS) and disease-free survival rates were significantly higher for patients within the up-to-seven criteria compared with those beyond (p = 0.034 and p = 0.001, respectively). Multivariate analysis revealed that low concentrations of des-γ-carboxy prothrombin (DCP) (<150 mAU/ml) and α-fetoprotein (AFP) (<100 ng/ml) were independent contributors to better OS of patients within or beyond the up-to-seven criteria, respectively. Accordingly, the patients were classified as follows: group A (patients within the up-to-seven criteria with DCP <150 mAU/ml), group C (patients beyond the up-to-seven criteria with AFP ≥100 ng/ml), and group B (other patients). OS differed significantly among groups (p < 0.001), and the median survival times of group A, B, and C were 4.2, 2.7, and 1.5 years, respectively. CONCLUSION The subclassification system incorporating the up-to-seven criteria combined with DCP and AFP levels may serve as better predictors of prognosis that may guide efforts to improve treatment strategies.
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Zhang YF, Zhou J, Wei W, Zou RH, Chen MS, Lau WY, Shi M, Guo RP. Intermediate-stage hepatocellular carcinoma treated with hepatic resection: the NSP score as an aid to decision-making. Br J Cancer 2016; 115:1039-1047. [PMID: 27701389 PMCID: PMC5117793 DOI: 10.1038/bjc.2016.301] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 07/05/2016] [Accepted: 08/29/2016] [Indexed: 01/27/2023] Open
Abstract
Background: The subgroups of patients with intermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) who would truly benefit from hepatic resection (HR) are unknown. An objective point score was established to guide the selection of these patients for HR. Methods: In all, 255 consecutive patients with intermediate-stage HCC treated with HR were evaluated retrospectively and included in this study (the training cohort). The variables on overall survival (OS, log-rank test) were investigated and a point score (the NSP score) was developed by using a Cox-regression model and validated in an independent external cohort from another institution (n=169). Results: The NSP score differentiated two groups of patients (⩽1, >1 point) with distinct prognoses (median OS, 61.3 vs 19.3 months; P<0.001). A high NSP score was associated with increased major adverse events after HR (5.6 vs 13.8%, P=0.027). Its predictive accuracy as determined by the area under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years (AUCs 0.688, 0.739, and 0.732) was greater than the other six staging systems for HCC (0.513–0.677). The findings were supported by the validation cohort. Conclusions: The NSP scoring system is more accurate in selecting patients with intermediate-stage HCC for HR.
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Affiliation(s)
- Yong-Fa Zhang
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Jie Zhou
- Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Wei Wei
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Ru-Hai Zou
- State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.,Department of Ultrasonography of Sun Yat-sen University Cancer Center, Guangzhou 510515, China
| | - Min-Shan Chen
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Wan Yee Lau
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,Department of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China
| | - Ming Shi
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Rong-Ping Guo
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, Guangzhou 510060, China.,State Key Laboratory of Oncology in South China, Guangzhou 510060, China.,Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
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Ramaswami R, Pinato DJ, Kubota K, Ishizuka M, Arizumi T, Kudo M, Jang JW, Kim YW, Pirisi M, Allara E, Sharma R. Prognostic sub-classification of intermediate-stage hepatocellular carcinoma: a multicenter cohort study with propensity score analysis. Med Oncol 2016; 33:114. [PMID: 27601241 PMCID: PMC5013141 DOI: 10.1007/s12032-016-0827-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 08/24/2016] [Indexed: 12/13/2022]
Abstract
There is significant heterogeneity in the clinicopathological characteristics of intermediate hepatocellular carcinoma (IHCC). This also translates to treatment as transarterial chemoembolization (TACE) is used as first-line therapy for patients with IHCC; however, in Asia liver resection (LR) is preferred. Prognostic tools are required to help guide clinicians in deciding treatment options. This study evaluates the prognostic impact of the Intermediate Stage Score (ISS) on overall survival (OS) in a large, multicenter cohort study of patients with IHCC treated with TACE or surgery LR. Consecutive patients from centers in Japan, Korea, Italy and the United Kingdom who underwent TACE or LR between 2001 and 2015 were enrolled. Propensity score (PS) adjustment was used to remove residual confounding and applied to LR (n = 162) and TACE (n = 449) to determine the prognostic significance of ISS. Among 611 patients, 75 % were men and 25 % women, with a mean age of 70 years. ISS is a valid prognostic tool in the BCLC-B population with a median OS ISS 1-51, 2-38.3, 3-24.3, 4-15.6, 5-16 months (p < 0.0001). ISS was analyzed within each treatment modality, and this was a valid prognostic score among those treated with TACE and LR (p < 0.001 vs. p = 0.008). In the PS-adjusted model, ISS retained its prognostic utility in TACE and LR groups (p < 0.001 vs. p = 0.007). ISS optimizes prognostic prediction in IHCC, reducing clinical heterogeneity, and is a useful tool for patients treated for TACE or LR.
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Affiliation(s)
- Ramya Ramaswami
- Department of Surgery and Cancer, Imperial College London Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
| | - David J Pinato
- Department of Surgery and Cancer, Imperial College London Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
- Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, UK
| | - Keiichi Kubota
- Department of Surgery, Dokkyo Medical University, Dokkyo, Japan
| | | | - Tadaaki Arizumi
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan
| | - Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Young Woon Kim
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Seoul, Republic of Korea
| | - Mario Pirisi
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy
- Interdisciplinary Research Center of Autoimmune Diseases, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy
| | - Elias Allara
- Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Via Solaroli 17, 28100, Novara, Italy
| | - Rohini Sharma
- Department of Surgery and Cancer, Imperial College London Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.
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39
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40
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Affiliation(s)
- Mario Angelico
- Liver and Transplant Unit, Fondazione Policlinico Tor Vergata, Tor Vergata University, Medical School, Rome, Italy.
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Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. This cancer commonly arises against a background of chronic liver disease. As a result, a patient with HCC requires multidisciplinary care. Treatment options vary widely based on tumor burden and metastases. The most widely utilized staging system is the Barcelona Clinic Liver Cancer staging system, which recommends treatments based on tumor size and the underlying liver disease and functional status of the patient. Treatment options range from surgical resection or transplantation to locoregional therapies with modalities such as radiofrequency ablation and transarterial chemoembolization to systemic chemotherapies. Future care involves the development of combination therapies that afford the best tumor response, further clarification of the patients best suited for therapies and the development of new oral chemotherapeutic agents.
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Affiliation(s)
- Jennifer S Au
- Division of Gastroenterology and Hepatology, Scripps Clinic
| | - Catherine T Frenette
- Liver Transplantation, Center for Organ and Cell Transplantation, Scripps Clinic, La Jolla, CA, USA
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Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma. Am J Gastroenterol 2016; 111:70-7. [PMID: 26729544 DOI: 10.1038/ajg.2015.389] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 11/10/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group. METHODS We assessed the prognosis of 269 untreated HCC patients observed in the period 1987-2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compared the survival of the various substages. RESULTS Median survival progressively decreased from stage B1 (n=65, 24.2%: 25 months) through stages B2 (n=105, 39.0%: 16 months) and B3 (n=22, 8.2%: 9 months), to stage B4 (n=77, 28.6%: 5 months; P<0.0001). Moreover, we observed a significantly different survival between contiguous stages (B1 vs. B2, P=0.0002; B2 vs. B3, P<0.0001; B3 vs. B4, P=0.0219). In multivariate analysis, the BCLC B subclassification (P<0.0001), MELD score (P=0.0013), and platelet count (P=0.0252) were independent predictors of survival. CONCLUSIONS The subclassification of the intermediate-stage HCC predicts the prognosis of patients with untreated HCC. The prognostic figures identified in this study may be used as a benchmark to assess the efficacy of therapeutic intervention in the various BCLC B substages, whereas it remains to be established whether incorporation of the MELD score might improve the prognosis of treated patients.
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Yamakado K, Hirota S. Sub-classification of intermediate-stage (Barcelona Clinic Liver Cancer stage-B) hepatocellular carcinomas. World J Gastroenterol 2015; 21:10604-10608. [PMID: 26457020 PMCID: PMC4588082 DOI: 10.3748/wjg.v21.i37.10604] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 06/17/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the fifth most common cancer in the world, shows increasing incidence worldwide. Curative treatments such as hepatectomy, liver transplantation, and radiofrequency ablation are applied in only 30%-60% of cases. Most remaining patients receive transarterial chemoembolization (TACE). Patients with intermediate-stage HCCs are regarded as good candidates for TACE. However, the intermediate stage includes non-homogeneous patients. Some movements are underway to stratify patients using prognostic factors to identify patient groups exhibiting greater benefit from TACE than other patient groups. This review describes two substaging systems that subclassify intermediate-stage HCCs and discusses the importance of dividing intermediate-stage patients.
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Han K, Kim JH. Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system. World J Gastroenterol 2015; 21:10327-10335. [PMID: 26420959 PMCID: PMC4579879 DOI: 10.3748/wjg.v21.i36.10327] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/11/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the fifth most common cancer that predominantly occurs in liver cirrhosis patients, requires staging systems to design treatments. The barcelona clinic liver cancer staging system (BCLC) is the most commonly used HCC management guideline. For BCLC stage B (intermediate HCC), transarterial chemoembolization (TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0 (very early HCC), TACE could be an alternative for patients unsuitable for radiofrequency ablation (RFA) or hepatic resection. In patients with BCLC stage A, TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B, TACE provides survival benefits compared with supportive care options. However, because of the substantial heterogeneity in the patient population with this stage, a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally, TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together, TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.
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Sieghart W, Hucke F, Peck-Radosavljevic M. Transarterial chemoembolization: modalities, indication, and patient selection. J Hepatol 2015; 62:1187-95. [PMID: 25681552 DOI: 10.1016/j.jhep.2015.02.010] [Citation(s) in RCA: 245] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 01/26/2015] [Accepted: 02/05/2015] [Indexed: 02/06/2023]
Abstract
Transarterial chemoembolization (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma (BCLC B). Further improvement of the use of TACE was the subject of intense clinical research over the past years. The introduction of DEB-TACE brought more technical standardization and reduction of TACE related toxicity. The use of dynamic radiologic response evaluation criteria (EASL, mRECIST), uncovered the prognostic significance of objective tumor response. Finally, new approaches for better patient selection for initial and subsequent TACE treatment schedules will limit the use of TACE to some extent but have the potential to improve outcome for patients at risk for TACE-induced harm.
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Affiliation(s)
- Wolfgang Sieghart
- Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Liver Cancer (HCC)-Study Group, Medical University Vienna, Austria.
| | - Florian Hucke
- Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Liver Cancer (HCC)-Study Group, Medical University Vienna, Austria
| | - Markus Peck-Radosavljevic
- Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Liver Cancer (HCC)-Study Group, Medical University Vienna, Austria.
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Ogasawara S, Chiba T, Ooka Y, Kanogawa N, Motoyama T, Suzuki E, Tawada A, Azemoto R, Shinozaki M, Yoshikawa M, Yokosuka O. A prognostic score for patients with intermediate-stage hepatocellular carcinoma treated with transarterial chemoembolization. PLoS One 2015; 10:e0125244. [PMID: 25919025 PMCID: PMC4412579 DOI: 10.1371/journal.pone.0125244] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 03/22/2015] [Indexed: 02/06/2023] Open
Abstract
Background Intermediate-stage hepatocellular carcinoma (HCC), defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system, is a heterogeneous condition with variable clinical benefits from transarterial chemoembolization (TACE). This study aimed to develop a simple validated prognostic score based on the predictive factors for survival in patients with intermediate-stage HCC treated with TACE. Methods Three-hundred and fifty patients with intermediate-stage HCC undergoing initial TACE at Chiba University Hospital (training cohort; n = 187) and two affiliated hospitals (validation cohort; n = 163) were included. Following variables were entered into univariate and multivariate Cox regression models to develop a points-based clinical scoring system: gender, age, etiology, pretreatment, Child–Pugh score, aspartate aminotransferase, creatinine, C-reactive protein, alfa-fetoprotein, size of the largest lesion, and number and location of lesions. Results The number of lesions and the Child–Pugh score were identified as independent prognostic factors in the training cohort. The development of a 0–7-point prognostic score, named the Chiba HCC in intermediate-stage prognostic (CHIP) score, was based on the sum of three subscale scores (Child–Pugh score = 0, 1, 2, or 3, respectively, number of lesions = 0, 2, or 3, respectively, HCV-RNA positivity = 0 or 1, respectively). The generated scores were then differentiated into five groups (0–2 points, 3 points, 4 points, 5 points, and 6–7 points) by the median survival time (65.2, 29.2, 24.3, 13.1, and 8.4 months, respectively; p < 0.0001). These results were confirmed in the external validation cohort (p < 0.0001). Conclusions The CHIP score is easy-to-use and may assist in finding an appropriate treatment strategy for intermediate-stage HCC.
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Affiliation(s)
- Sadahisa Ogasawara
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tetsuhiro Chiba
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
- * E-mail:
| | - Yoshihiko Ooka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Naoya Kanogawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Tenyu Motoyama
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Eiichiro Suzuki
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Akinobu Tawada
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Ryosaku Azemoto
- Department of Gastroenterology, Kimitsu Chuo Hospital, Chiba, Japan
| | - Masami Shinozaki
- Department of Gastroenterology, Numazu City Hospital, Shizuoka, Japan
| | - Masaharu Yoshikawa
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Scaffaro LA, Stella SF, Alvares-Da-Silva MR, Kruel CDP. Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma. World J Hepatol 2015; 7:628-632. [PMID: 25848487 PMCID: PMC4381186 DOI: 10.4254/wjh.v7.i3.628] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2014] [Revised: 01/08/2015] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the survival rates after transarterial embolization (TAE).
METHODS: One hundred third six hepatocellular carcinoma (HCC) patients [90 barcelona clinic liver cancer (BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.
RESULTS: The overall mean survival was 35.8 mo (95%CI: 25.1-52.0). The survival rates of the BCLC A patients (33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo (95%CI: 27.5-52.0). The survival rates of the BCLC B patients (66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo (95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo (95%CI: 32.8-34.3), 28.6 mo (95%CI: 27.5-29.8), 19.0 mo (95%CI: 17.2-20.9) and 13 mo, respectively (P = 0.013).
CONCLUSION: The BCLC sub-staging system could add additional prognosis information for post-embolization survival rates in HCC patients.
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Kinoshita A, Onoda H, Fushiya N, Koike K, Nishino H, Tajiri H. Staging systems for hepatocellular carcinoma: Current status and future perspectives. World J Hepatol 2015; 7:406-424. [PMID: 25848467 PMCID: PMC4381166 DOI: 10.4254/wjh.v7.i3.406] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 11/08/2014] [Accepted: 12/10/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major health concern worldwide and the third cause of cancer-related death. Despite advances in treatment as well as careful surveillance programs, the mortality rates in most countries are very high. In contrast to other cancers, the prognosis and treatment of HCC depend on the tumor burden in addition to patient’s underlying liver disease and liver functional reserve. Moreover, there is considerable geographic and institutional variation in both risk factors attributable to the underlying liver diseases and the management of HCC. Therefore, although many staging and/or scoring systems have been proposed, there is currently no globally accepted system for HCC due to the extreme heterogeneity of the disease. The aim of this review is to focus on currently available staging systems as well as those newly reported in the literatures since 2012. Moreover, we describe problems with currently available staging systems and attempts to modify and/or add variables to existing staging systems.
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Wang JH, Kee KM, Lin CY, Hung CH, Chen CH, Lee CM, Lu SN. Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma. J Gastroenterol Hepatol 2015; 30:358-63. [PMID: 25088668 DOI: 10.1111/jgh.12686] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/07/2014] [Indexed: 01/27/2023]
Abstract
BACKGROUND AND AIM Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal. METHODS Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. RESULTS Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P < 0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P = 0.174), and B2b and B3 (P = 0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b + B2a), mB3 (B2b + B3). The modified substages (mB1-mB3) showed a more desirable substaging system. CONCLUSIONS For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.
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Affiliation(s)
- Jing-Houng Wang
- Department of Internal Medicine, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Heterogeneity of intermediate-stage HCC necessitates personalized management including surgery. Nat Rev Clin Oncol 2014; 12:10. [PMID: 25421283 DOI: 10.1038/nrclinonc.2014.122-c1] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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