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Lee SM, Choi JH, Yoon JH, Kim YJ, Yu SJ, Lee JH, Kang HC, Chie EK, Kim KS. Efficacy and safety of image-guided hypofractionated radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective, multicenter study. BMC Cancer 2025; 25:736. [PMID: 40254568 PMCID: PMC12010600 DOI: 10.1186/s12885-025-13739-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 02/14/2025] [Indexed: 04/22/2025] Open
Abstract
BACKGROUND External beam radiation therapy (RT) has shown promising effects for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) in recent studies. However, there is still a lack of consensus on the optimal RT scheme for PVTT treatment. We evaluated the efficacy and safety of image-guided 10-fraction hypofractionated RT in these patients. METHODS Between January 2016 and March 2022, a total of 95 HCC patients with PVTT received 10-fraction hypofractionated image-guided radiation therapy (IGRT) at two institutes, and 69 patients were analyzed. Follow-up imaging was performed at three-month intervals after the completion of RT. The extent of PVTT was described according to the Liver Cancer Study Group of Japan classification: Vp1 = segmental portal vein branch, Vp2 = right/left anterior/posterior portal vein, Vp3 = right/left portal vein, and Vp4 = main portal vein. Response evaluation was performed using Response Evaluation Criteria in Solid Tumors, version 1.1. Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) were calculated from the start date of RT. RESULTS The median prescribed dose of 50 Gy (range: 40-50 Gy; biologically effective dose [BED]: 56-75Gy10) was delivered in 10 fractions. In this cohort, 4.3% of patients had Vp1, 20.3% had Vp2, 37.7% had Vp3, and 37.7% had Vp4. Median Planning target volume was 105.3 cc (interquartile range [IQR], 74.1-179.4 cc). Fifty-two (75.4%) patients received 50 Gy. With a median follow-up of 10.2 months (IQR, 6-21 months), the median OS was 20.3 months, and 1-year FFLP, PFS, and OS rates were 88.7%, 26.9%, and 62.2%, respectively. At 3 months follow-up, 13.0% had a complete response, 36.2% had a partial response, 46.4% had a stable disease and 4.4% had a progressive disease. In the multivariate analysis, alpha-fetoprotein level ≥ 600 IU/ml (hazard ratio [HR] 2.06, p = 0.03), Child-Pugh Class B or C (HR 2.30, p = 0.02), and stage IVA or IVB (4.05, p = 0.02) were significantly related to OS. During the follow-up period, there were 2 (2.9%) cases of grade ≥ 3 toxicity: grade 3 liver enzyme elevation (n = 1), and acute cholangitis (n = 1). CONCLUSIONS Hypofractionated RT demonstrated promising local PVTT control and OS rates with acceptable toxicity. These data suggest that 10-fraction image-guided hypofractionated RT (BED: 56-75 Gy10) is a feasible treatment option for PVTT in HCC patients.
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Affiliation(s)
- Sang Min Lee
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin Hwa Choi
- Department of Radiation Oncology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Kyung Su Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Ishida T, Mizumoto M, Saito T, Okumura T, Miura K, Makishima H, Iizumi T, Numajiri H, Baba K, Murakami M, Nakamura M, Nakai K, Sakurai H. Proton Beam Therapy for Treating Patients with Hepatocellular Carcinoma with Major Portal Vein Tumor Invasion: A Single Center Retrospective Study. Cancers (Basel) 2024; 16:2050. [PMID: 38893169 PMCID: PMC11171269 DOI: 10.3390/cancers16112050] [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: 04/27/2024] [Revised: 05/27/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) has a poor prognosis and is generally not indicated for surgery. Proton beam therapy (PBT) may offer an alternative treatment. In this study, long-term outcomes were examined in 116 patients (median age 66 years, 100 males) with HCC with advanced PVTT (Vp3 or Vp4) who received PBT from April 2008 to March 2018. Of these patients, 63 received PBT as definitive treatment and 53 as palliative treatment. The representative dose was 72.6 Gy (RBE) in 22 fractions. Eight patients died in follow-up, including 72 due to tumor progression. The 5-year overall survival (OS) rate was 18.0% (95% CI 9.8-26.2%) and the 5-year local control (LC) rate was 86.1% (74.9-97.3%). In multivariate analyses, performance status and treatment strategy were significantly associated with OS. The median follow-up period for survivors with definitive treatment was 33.5 (2-129) months, and the 5-year OS rate was 25.1% (12.9-37.3%) in these cases. The median survival time after definitive irradiation was >20 months. The 5-year OS rate was 9.1% (0-19.7%) for palliative irradiation. These results compare favorably with those of other therapies and suggest that PBT is a useful option for cases of HCC with advanced PVTT that cannot undergo surgery, with an expected survival benefit and good local control. Determining the optimal indication for this treatment is a future challenge.
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Affiliation(s)
- Toshiki Ishida
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Masashi Mizumoto
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Takashi Saito
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Toshiyuki Okumura
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
- Department of Radiation Oncology, Ibaraki Prefectural Central Hospital, Ibaraki 309-1703, Japan
| | - Kosei Miura
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
- Department of Radiation Oncology, JCHO Tokyo Shinjuku Medical Center, Tokyo 162-8543, Japan
| | - Hirokazu Makishima
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Takashi Iizumi
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Haruko Numajiri
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Keiichiro Baba
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Motohiro Murakami
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Masatoshi Nakamura
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Kei Nakai
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
| | - Hideyuki Sakurai
- Department of Radiation Oncology, University of Tsukuba Hospital, 2-1-1 Tsukuba, Ibaraki 305-8576, Japan; (T.I.); (T.S.); (T.O.); (K.M.); (H.M.); (T.I.); (H.N.); (K.B.); (M.M.); (M.N.); (K.N.); (H.S.)
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Hwang SY, Woo HY, Heo J, Kim HJ, Park YJ, Yi KY, Lee YR, Park SY, Chung WJ, Jang BK, Tak WY. Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:838. [PMID: 38398229 PMCID: PMC10887033 DOI: 10.3390/cancers16040838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/15/2024] [Accepted: 02/17/2024] [Indexed: 02/25/2024] Open
Abstract
Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.
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Affiliation(s)
- Sang Youn Hwang
- Department of Internal Medicine, Dongnam Institute of Radiologic & Medical Sciences, Busan 46033, Republic of Korea; (S.Y.H.); (H.J.K.)
| | - Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea; (H.Y.W.); (Y.J.P.); (K.Y.Y.)
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea; (H.Y.W.); (Y.J.P.); (K.Y.Y.)
| | - Hyung Jun Kim
- Department of Internal Medicine, Dongnam Institute of Radiologic & Medical Sciences, Busan 46033, Republic of Korea; (S.Y.H.); (H.J.K.)
| | - Young Joo Park
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea; (H.Y.W.); (Y.J.P.); (K.Y.Y.)
| | - Ki Youn Yi
- Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea; (H.Y.W.); (Y.J.P.); (K.Y.Y.)
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea; (Y.R.L.); (S.Y.P.)
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea; (Y.R.L.); (S.Y.P.)
| | - Woo Jin Chung
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea; (W.J.C.); (B.K.J.)
| | - Byoung Kuk Jang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea; (W.J.C.); (B.K.J.)
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea; (Y.R.L.); (S.Y.P.)
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Qiu X, Cai J, Chen H, Yao J, Xiao C, Li R, Xiao J, Zhang J, Sui X, Lu T, Zheng J, Zhang Y, Yang Y. Chemotherapy combined with radiotherapy can benefit more unresectable HCC patients with portal and/or hepatic vein invasion: a retrospective analysis of the SEER database. Front Oncol 2023; 13:1098686. [PMID: 37409255 PMCID: PMC10319410 DOI: 10.3389/fonc.2023.1098686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 05/15/2023] [Indexed: 07/07/2023] Open
Abstract
Background The purpose of this study is to evaluate the effects of chemotherapy and radiotherapy on the prognosis of unresectable HCC patients with portal and/or hepatic vein invasion. Methods A retrospective analysis of unresectable HCC patients with portal and/or hepatic vein invasion registered in the Surveillance, Epidemiology, End Results (SEER) database was performed. The propensity score-matching (PSM) method was used to balance differences between groups. Overall survival (OS) and cancer-specific survival (CSS) were the interesting endpoints. OS was calculated from the date of diagnosis to the date of death caused by any cause or the last follow-up. CSS was defined as the interval between the date of diagnosis and date of death due only to HCC or last follow-up. OS and CSS were analyzed by using Kaplan-Meier analysis, Cox proportional hazards model, and Fine-Gray competing-risk model. Results A total of 2,614 patients were included. 50.2% patients received chemotherapy or radiotherapy and 7.5% patients received both chemotherapy and radiotherapy. Compared to the untreated group, chemotherapy or radiotherapy (COR) (HR = 0.538, 95% CI 0.495-0.585, p < 0.001) and chemotherapy and radiotherapy (CAR) (HR = 0.371, 95% CI 0.316-0.436, p < 0.001) showed better OS. In the COR group, Cox analysis results showed AFP, tumor size, N stage and M stage were independent risk factor of OS. Competing-risk analysis results showed AFP, tumor size and M stage were independent risk factor of CSS. In the CAR group, AFP and M stage were independent risk factors of OS. Competing-risk analysis results showed M stage were independent risk factor of CSS. Kaplan Meier analysis showed chemotherapy combined with radiotherapy significantly improves OS (10.0 vs. 5.0 months, p < 0.001) and CSS (10.0 vs. 6.0 months, p = 0.006) than monotherapy. Conclusion AFP positive and distant metastasis are the main risk factors affecting OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion. Chemotherapy combined with radiotherapy significantly improves OS and CSS of unresectable HCC patients with portal and/or hepatic vein invasion.
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Affiliation(s)
- Xiaotong Qiu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Jianye Cai
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Haitian Chen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Jia Yao
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Cuicui Xiao
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
- Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rong Li
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Jiaqi Xiao
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Jiebin Zhang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Xin Sui
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
- Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Tongyu Lu
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Jun Zheng
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Yingcai Zhang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Province Key Laboratory of Liver Disease Research, Guangzhou, China
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Park S, Kim S, Koun S, Park HC, Yoon WS, Rim CH. Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish. Int J Radiat Biol 2022; 99:845-852. [PMID: 36318746 DOI: 10.1080/09553002.2023.2142982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
PURPOSE The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. METHODS Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. RESULTS The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1β and IL-6) compared to the radiation alone group (p<.05). CONCLUSION The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.
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Affiliation(s)
- Sunmin Park
- Department of Radiation Oncology, Korea University Ansan Hospital, Gyeonggido, Republic of Korea
| | - Suhyun Kim
- Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea
- Zebrafish Translational Medical Research Center, Korea University, Ansan, Republic of Korea
| | - Soonil Koun
- Zebrafish Translational Medical Research Center, Korea University, Ansan, Republic of Korea
| | - Hae-Chul Park
- Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea
- Zebrafish Translational Medical Research Center, Korea University, Ansan, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Gyeonggido, Republic of Korea
- Department of Radiation Oncology, College of Medicine, Korea University, Seoul, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Gyeonggido, Republic of Korea
- Department of Radiation Oncology, College of Medicine, Korea University, Seoul, Republic of Korea
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 170] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Naruto K, Kawaoka T, Kodama K, Ogawa Y, Amioka K, Yoshikawa Y, Kikukawa C, Suehiro Y, Yamaoka K, Ando Y, Kosaka Y, Uchikawa S, Nakahara T, Murakami E, Ono A, Uchida T, Yamauchi M, Okamoto W, Takahashi S, Imamura M, Chosa K, Awai K, Kubo K, Nagata Y, Chayama K, Aikata H. Efficacy and safety of chemoradiation therapy using one-shot cisplatin via hepatic arterial infusion for advanced hepatocellular carcinoma with major macrovascular invasion: a single-arm retrospective cohort study. BMC Gastroenterol 2022; 22:275. [PMID: 35655156 PMCID: PMC9161561 DOI: 10.1186/s12876-022-02359-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 05/24/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) who receive systemic chemotherapy have a poor prognosis. This study aimed to determine if one-shot cisplatin (CDDP) chemotherapy via hepatic arterial infusion (HAI) combined with radiation therapy (RT) prior to systemic chemotherapy could improve the outcomes of these patients.
Methods
This study consisted of 32 HCC patients with the following eligibility criteria: (i) portal vein invasion 3/4 and/or hepatic vein invasion 2/3; (ii) received one-shot CDDP via HAI; (iii) received RT for MVI, (iv) a Child–Pugh score ≤ 7; and (v) an Eastern Clinical Oncology Group Performance Status score of 0 or 1. To determine the therapeutic effect, we collected information on patient characteristics and took contrast-enhanced computed tomography at the start of the therapy and every 2 to 4 months after the start of therapy. We evaluated the overall response of the tumor and tumor thrombosis according to modified Response Evaluation Criteria in Solid Tumors. We assessed patient data using the Mann–Whitney U and Fisher exact tests and evaluated overall survival and progression-free survival using the log-rank test.
Results
The overall response rate at the first evaluation performed a median of 1.4 weeks after HAI was 16% for the main intrahepatic tumor and 59% for the MVI. The best responses were the same as those of the first-time responses. The duration of median survival was 8.6 months, and progression-free survival of the main intrahepatic tumor was 3.2 months. Predictive factors for overall survival were the relative tumor volume in the liver and the first therapeutic response of MVI. There were no severe adverse events or radiation-induced hepatic complications.
Conclusions
One-shot CDDP via HAI and RT were well tolerated and showed immediate and favorable control of MVI. Thus, this combination shows potential as a bridging therapy to systemic chemotherapy.
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10
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Tao ZW, Cheng BQ, Zhou T, Gao YJ. Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review. Hepatobiliary Pancreat Dis Int 2022; 21:134-144. [PMID: 34955380 DOI: 10.1016/j.hbpd.2021.12.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/05/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.
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Affiliation(s)
- Zi-Wen Tao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Bao-Quan Cheng
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Tao Zhou
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
| | - Yan-Jing Gao
- Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
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11
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Tong VJW, Shelat VG, Chao YK. Clinical application of advances and innovation in radiation treatment of hepatocellular carcinoma. J Clin Transl Res 2021; 7:811-833. [PMID: 34988334 PMCID: PMC8715712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 09/22/2021] [Accepted: 09/29/2021] [Indexed: 02/08/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) management has evolved over the past two decades, with the development of newer treatment modalities. While various options are available, unmet needs are reflected through the mixed treatment outcome for intermediate-stage HCC. As HCC is radiosensitive, radiation therapies have a significant role in management. Radiation therapies offer local control for unresectable lesions and for patients who are not surgical candidates. Radiotherapy also provides palliation in metastatic disease, and acts as a bridge to resection and transplantation in selected patients. Advancements in radiotherapy modalities offer improved dose planning and targeted delivery, allowing for better tumor response and safer dose escalations while minimizing the risks of radiation-induced liver damage. Radiotherapy modalities are broadly classified into external beam radiation therapy and selective internal radiation therapy. With emerging modalities, radiotherapy plays a complementary role in the multidisciplinary care of HCC patients. Aim We aim to provide an overview of the role and clinical application of radiation therapies in HCC management. Relevance for Patients The continuous evolution of radiotherapy techniques allows for improved therapeutic outcomes while mitigating unwanted adverse effects, making it an attractive modality in HCC management. Rigorous clinical studies, quality research and comprehensive datasets will further its application in the present era of evidence-based practice in Medicine.
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Affiliation(s)
- Valerie J. W. Tong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Vishal G. Shelat
- Department of General Surgery, Tan Tock Seng Hospital, 308433, Singapore
| | - Yew Kuo Chao
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 308433, Singapore
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12
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Khorprasert C, Thonglert K, Alisanant P, Amornwichet N. Advanced radiotherapy technique in hepatocellular carcinoma with portal vein thrombosis: Feasibility and clinical outcomes. PLoS One 2021; 16:e0257556. [PMID: 34555075 PMCID: PMC8460041 DOI: 10.1371/journal.pone.0257556] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 09/06/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single-institution. OBJECTIVES To examine clinical results in terms of overall survival (OS), local control (LC), response of primary tumor and PVTT, hepatic and gastrointestinal adverse reaction, and prognosis variables for OS and LC. MATERIALS AND METHODS Between July 2007 and August 2019, non-metastatic HCC with PVTT patients treated with RT were retrospectively reviewed and evaluated. RESULTS The analysis included data from 160 patients. The mean age of the patients was 60.8 years ((95% CI 58.2-62.0). The median diameter of the tumor was 7.7 cm (range: 1-24.5). 85 (54.5%) individuals had PVTT in the main or first branch. At 1.8-10 Gy per fraction, the mean biologically effective dose (BED) as α/β ratio of 10 was 49.6 (95% CI 46.7-52.5) Gy10. The median survival time was 8.3 (95% CI 6.1-10.3) months. Survival rates at one and two years were 39.6% and 17.1%, respectively. Estimated incidence of local failure using competing risk analysis were 24% and 60% at 1 and 2 years, respectively. The overall response rate was 74%, with an 18.5 percent complete response rate. In multivariate analysis, tumor size, overall response, and radiation dose were all significant prognostic variables for OS. Hepatic unfavorable events of grade 3 and 4 were for 14.1% of the total. There was no occurrences of grade 3-4 gastrointestinal toxicity, either acute or late. Additionally, there were no treatment-related mortality. CONCLUSIONS Advanced RT is regarded as a safe and effective therapeutic option for HCC with PVTT. Overall survival was clearly related to tumor size, radiation dose, and tumor/PVTT response. Individuals with BED 56 Gy10 had significantly better overall survival than patients with BED 56 Gy10. A prospective randomized trial is required to validate these outcomes in order to corroborate these findings.
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Affiliation(s)
- Chonlakiet Khorprasert
- Faculty of Medicine, Division of Radiation Oncology, Department of Radiology, Chulalongkorn University, Bangkok, Thailand
| | - Kanokphorn Thonglert
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Petch Alisanant
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Napapat Amornwichet
- Faculty of Medicine, Division of Radiation Oncology, Department of Radiology, Chulalongkorn University, Bangkok, Thailand
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13
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Successful multimodality treatment for advanced hepatocellular carcinoma with tumor thrombosis of the main portal trunk: a case study. Clin J Gastroenterol 2021; 14:1517-1524. [PMID: 34291386 DOI: 10.1007/s12328-021-01481-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/11/2021] [Indexed: 10/20/2022]
Abstract
The overall survival of patients with advanced hepatocellular carcinoma with tumor thrombosis of the main trunk or bilobar branches of the portal vein is extremely poor. Moreover, there is no standard treatment established for the condition. Herein, we present the case of a 65-year-old man who were treated the patient with hepatic arterial infusion chemotherapy, radiation therapy for tumor thrombosis, portal vein stent placement, lenvatinib administration, and renal venous shunt embolization. A complete response was observed according to mRECIST and the patient has been alive for 14 months since treatment initiation with no tumor recurrence.
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14
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Choi HS, Kang KM, Jeong BK, Jeong H, Lee YH, Ha IB, Song JH. Effectiveness of stereotactic body radiotherapy for portal vein tumor thrombosis in patients with hepatocellular carcinoma and underlying chronic liver disease. Asia Pac J Clin Oncol 2021; 17:209-215. [PMID: 32757461 DOI: 10.1111/ajco.13361] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 04/14/2020] [Indexed: 01/14/2023]
Abstract
AIM Stereotactic-body radiotherapy (SBRT) is a treatment option for portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC). Here, we report on our experience of treating PVTT using SBRT in patients with concomitant underlying chronic liver disease. METHODS This study included 24 patients. The initial prescription dose was 45 Gy in three fractions in 17 (70.8%) patients, but it was modified in the remaining seven (29.2%) patients, with the dose ranging from 39 to 42 Gy in 3-4 fractions. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients. RESULTS Of the 24 patients, 2 (8.3%) showed complete response, while 11 (45.8%) showed partial response. After a median follow-up of 8.4 months (range: 2.6-56.5 months), the 1-year overall survival (OS) and the median survival were 67.5% and 20.8 months, respectively. Both combined SBRT and TACE and grade ≥3 hepatic toxicity affected the 1-year OS (SBRT alone vs SBRT + TACE: 14.6% vs 71.4%, P < .001; presence of hepatic toxicity vs absence: 0% vs 81.1%, P = .002). CONCLUSIONS Overall, SBRT, especially in combination with TACE, is an effective treatment for patients with HCC and PVTT. An optimal dose schedule must be followed to reduce hepatic toxicity while maintaining tumor response.
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Affiliation(s)
- Hoon Sik Choi
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Ki Mun Kang
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Bae Kwon Jeong
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Hojin Jeong
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Yun Hee Lee
- Department of Radiation Oncology, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Republic of Korea
| | - In Bong Ha
- Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Jin Ho Song
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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15
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Kosaka Y, Kimura T, Kawaoka T, Ogawa Y, Amioka K, Naruto K, Yoshikawa Y, Kikukawa C, Suehiro Y, Yamaoka K, Ando Y, Uchikawa S, Morio K, Nakahara T, Murakami E, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chosa K, Awai K, Nagata Y, Chayama K, Aikata H. Hepatic Arterial Infusion Chemotherapy Combined with Radiation Therapy for Advanced Hepatocellular Carcinoma with Tumor Thrombosis of the Main Trunk or Bilobar of the Portal Vein. Liver Cancer 2021; 10:151-160. [PMID: 33977091 PMCID: PMC8077503 DOI: 10.1159/000513706] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/08/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Overall survival of patients with advanced hepatocellular carcinoma (HCC) with Vp4 (tumor thrombosis of the main trunk or bilobar of the portal vein) is extremely poor. PURPOSE The purpose of this study is to clarify the prognosis of hepatic arterial infusion chemotherapy (HAIC) combined with radiation therapy (RT) for advanced HCC with Vp4 and to analyze the factors that contribute to the prognosis. METHODS In this retrospective cohort study, 51 HCC patients who were treated with HAIC and RT for portal vein tumor thrombosis and met the following criteria were enrolled: (i) with Vp4; (ii) Child-Pugh score of 5-7; (iii) Eastern Cooperative Oncology Group performance status of 0 or 1; (iv) no history of systemic therapy; and (v) from September 2004 to April 2019. RESULTS Median overall survival and median progression-free survival were 12.1 and 4.2 months, respectively. Multivariate analysis showed >50% of relative tumor volume in the liver (HR, 3.027; p = 0.008) and extrahepatic spread with (HR, 3.773; p = 0.040) as significant and independent factors of OS. The total overall response rate (ORR) was 19.6%; ORR in main tumor was 13.7%; and ORR in Vp4 was 51.0%. None of the patients who received HAIC combined with RT for advanced HCC with Vp4 developed hepatic failure. This combination therapy of HAIC with RT was safe and well tolerated in all cases. CONCLUSION Combination therapies of HAIC and RT might be good therapy for advanced HCC with Vp4.
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Affiliation(s)
- Yumi Kosaka
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kimura
- Therapeutic Radiology, Institute and Graduate School of Biomedical Science, and, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yutaro Ogawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Kei Amioka
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Kensuke Naruto
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yuki Yoshikawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Chihiro Kikukawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yosuke Suehiro
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Kenji Yamaoka
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Yuwa Ando
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Shoichi Takahashi
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan
| | - Keigo Chosa
- Diagnostic Radiology, and, Hiroshima University, Hiroshima, Japan
| | - Kazuo Awai
- Diagnostic Radiology, and, Hiroshima University, Hiroshima, Japan
| | - Yasushi Nagata
- Therapeutic Radiology, Institute and Graduate School of Biomedical Science, and, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan,Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan,Institute of Physical and Chemical Research (RIKEN) Center for Integrative Medical Sciences, Yokohama, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan,*Hiroshi Aikata, Division of Frontier Medical Science, Department of Medicine and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8551 (Japan),
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16
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Yang JF, Lo CH, Lee MS, Lin CS, Dai YH, Shen PC, Chao HL, Huang WY. Stereotactic ablative radiotherapy versus conventionally fractionated radiotherapy in the treatment of hepatocellular carcinoma with portal vein invasion: a retrospective analysis. Radiat Oncol 2019; 14:180. [PMID: 31640728 PMCID: PMC6805309 DOI: 10.1186/s13014-019-1382-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 09/23/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND This study aimed to compare the clinical outcomes of stereotactic ablative radiotherapy (SABR) and conventionally fractionated radiotherapy (CFRT) in hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). METHODS HCC patients with PVI treated with radiotherapy from 2007 to 2016 were analysed. CFRT was administered at a median dose of 51.5 Gy (interquartile range, 45-54 Gy) with 1.8-3 Gy per fraction. SABR was administered at a median dose of 45 Gy (interquartile range, 40-48 Gy) with 6-12.5 Gy per fraction. Treatment efficacy, toxicity, and associated predictors were assessed. RESULTS Among the 104 evaluable patients (45 in the SABR group and 59 in the CFRT group), the overall response rate (ORR, complete and partial response) was significantly higher in the SABR group than the CFRT group (62.2% vs. 33.8%, p = 0.003). The 1-year overall survival (OS) rate (34.9% vs. 15.3%, p = 0.012) and in-field progression-free survival (IFPS) rate (69.6% vs. 32.2%, p = 0.007) were also significantly higher in the SABR vs. CFRT group. All 3 rates remained higher in the SABR group after propensity score matching. Multivariable analysis identified SABR and a biologically effective dose ≥65 Gy as favourable predicators of OS. There was no difference between treatment groups in the incidence of radiation-induced liver disease or increase of Child-Pugh score ≥ 2 within 3 months of radiotherapy. CONCLUSIONS SABR was superior to CFRT in terms of ORR, OS, and IFPS. We suggest that SABR should be the preferred technique for HCC patients with PVI.
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Affiliation(s)
- Jen-Fu Yang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Cheng-Hsiang Lo
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Meei-Shyuan Lee
- School of Public Health, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Shu Lin
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Yang-Hong Dai
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Po-Chien Shen
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Hsing-Lung Chao
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kong Rd. Nei-Hu, 11490 Taipei, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
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17
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Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC, Lim YS. Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial. JAMA Oncol 2019; 4:661-669. [PMID: 29543938 DOI: 10.1001/jamaoncol.2017.5847] [Citation(s) in RCA: 307] [Impact Index Per Article: 51.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Importance Patients with hepatocellular carcinoma showing macroscopic vascular invasion have a poor prognosis. Sorafenib is the sole treatment option for these patients, with unsatisfactory response and survival benefit. Combined treatment with transarterial chemoembolization (TACE) plus external beam radiotherapy (RT) has shown promising results for these patients in observational studies. Objective To evaluate the efficacy and safety of TACE plus RT compared with sorafenib for patients with hepatocellular carcinoma and macroscopic vascular invasion. Design, Setting, and Participants In this randomized, open-label clinical trial conducted at an academic tertiary care center between July 1, 2013, and October 31, 2016, 90 treatment-naive patients with liver-confined hepatocellular carcinoma showing macroscopic vascular invasion were randomly assigned to receive sorafenib (400 mg twice daily; 45 participants [the sorafenib group]) or TACE (every 6 weeks) plus RT (within 3 weeks after the first TACE, maximum 45 Gy with the fraction size of 2.5 to 3 Gy; 45 participants [the TACE-RT group]). Main Outcomes and Measures The primary end point was the 12-week progression-free survival rate by intention-to-treat analysis. Radiologic response was assessed by independent review according to the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Treatment crossover was permitted after confirming disease progression. Results Of the 90 patients (median age, 55 years; range, 33-82 years), 77 were men and 13 were women. All patients had portal vein invasion of hepatocellular carcinoma and Child-Pugh class A liver function. The median maximal tumor diameter was 9.7 cm. Most patients (71 [78.9%]) had multiple lesions. At week 12, the progression-free survival rate was significantly higher in the TACE-RT group than the sorafenib group (86.7% vs 34.3%; P < .001). The TACE-RT group showed a significantly higher radiologic response rate than the sorafenib group at 24 weeks (15 [33.3%] vs 1 [2.2%]; P < .001), a significantly longer median time to progression (31.0 vs 11.7 weeks; P < .001), and significantly longer overall survival (55.0 vs 43.0 weeks; P = .04). Curative surgical resection was conducted for 5 patients (11.1%) in the TACE-RT group owing to downstaging. No patients in the TACE-RT group discontinued treatment owing to hepatic decompensation. Conclusions and Relevance For patients with advanced hepatocellular carcinoma showing macroscopic vascular invasion, first-line treatment with TACE plus RT was well tolerated and provided an improved progression-free survival, objective response rate, time to progression, and overall survival compared with sorafenib treatment. Trial Registration clinicaltrials.gov Identifier: NCT01901692.
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Affiliation(s)
- Sang Min Yoon
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Jung Lee
- Department of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ji Hoon Shin
- Department of Radiology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ji Hyun An
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol 2019; 25:4360-4382. [PMID: 31496618 PMCID: PMC6710186 DOI: 10.3748/wjg.v25.i31.4360] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
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MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Contrast Media/administration & dosage
- Disease-Free Survival
- Hepatectomy
- Humans
- Hypertension, Portal/etiology
- Hypertension, Portal/mortality
- Hypertension, Portal/therapy
- Liver Neoplasms/complications
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Liver Transplantation
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Patient Selection
- Portal Vein/diagnostic imaging
- Portal Vein/pathology
- Prognosis
- Survival Analysis
- Thrombectomy
- Time Factors
- Ultrasonography/methods
- Venous Thrombosis/etiology
- Venous Thrombosis/mortality
- Venous Thrombosis/therapy
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Affiliation(s)
- Lucia Cerrito
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Brigida Eleonora Annicchiarico
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maurizio Pompili
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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Lee V, Seong J, Yoon S, Wong T, Wang B, Zhang J, Chiang C, Ho P, Dawson L. Contrasting Some Differences in Managing Advanced Unresectable Hepatocellular Carcinoma Between the East and the West. Clin Oncol (R Coll Radiol) 2019; 31:560-569. [DOI: 10.1016/j.clon.2019.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 05/28/2019] [Accepted: 05/29/2019] [Indexed: 02/07/2023]
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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Lee J, Yoon JS, Kim JS, Koom WS, Cho J, Suh CO. Long-term outcome, relapse patterns, and toxicity after radiotherapy for orbital mucosa-associated lymphoid tissue lymphoma: implications for radiotherapy optimization. Jpn J Clin Oncol 2019; 49:664-670. [PMID: 31505651 DOI: 10.1093/jjco/hyz044] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 02/15/2019] [Accepted: 03/05/2019] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVES Although mucosa-associated lymphoid tissue lymphoma (MALToma) is sensitive to radiation therapy (RT), the optimal RT dose and treatment volumes have not been established. This study aimed to assess the relapse patterns and outcomes of patients with orbital MALToma who underwent RT and to suggest implications for optimized RT. METHODS We reviewed 212 patients (246 orbits) diagnosed with orbital MALToma who received RT between 1993 and 2013. Median RT dose was 25.2 Gy. Generally, conjunctival and eyelid lesions were irradiated with electrons, whereas retrobulbar and lacrimal gland lesions with photons. Lens shielding was used for 70% of treated eyes, mainly conjunctival and eyelid tumors. RESULTS Relapse occurred in 29 patients. Among 11 patients with local relapse (LR), 4 were attributed to insufficient dose (n = 2) and improper RT volume (n = 2). The 10-year LR, contralateral orbit relapse, and distant relapse rates were 8.6%, 12.8% and 4.9%, respectively. Twelve patients died of disease-specific causes (n = 1) and intercurrent diseases (n = 11). The 10-year relapse-free survival, overall survival, and cause-specific survival rates were 69.7%, 88.2% and 98.8%, respectively. Grade 3 cataracts and nasolacrimal duct obstruction were observed in 27 and 4 orbits, respectively. CONCLUSION Low-dose RT with proper lens shielding is an appropriate treatment for orbital MALToma in terms of high disease control rate and acceptable morbidity. However, lower RT dose may be attempted to further reduce toxicity while maintaining excellent outcomes.
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Affiliation(s)
- Jeongshim Lee
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Radiation Oncology, Inha University Hospital, Incheon, Republic of Korea
| | - Jin Sook Yoon
- Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Seok Kim
- Division of Hemato-oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeho Cho
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang-Ok Suh
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
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22
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 240] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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Lee J, Yoon WS, Koom WS, Rim CH. Role of local treatment including radiotherapy in Barcelona Clinic of Liver Cancer stage C patients: a nationwide cohort analysis in South Korea. Cancer Manag Res 2019; 11:1373-1382. [PMID: 30809102 PMCID: PMC6376887 DOI: 10.2147/cmar.s193761] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Purpose Sorafenib is recommended as the standard treatment for hepatocellular carcinoma (HCC) of Barcelona Clinic of Liver Cancer stage C (BCLC C). However, local treatment including radiation therapy (LRT) is also widely administered in practice. The aim of our study was to define the role of LRT among BCLC C patients. Patients and methods Of the patients with HCC enrolled the Korean Central Cancer Registry from 2008 to 2014, the Korean Liver Cancer Study Group randomly extracted 10,580 patient data from ~50 hospitals nationwide. Among them, 3,401 patients were categorized to have BCLC C HCC. Among them, patients with information on initial treatments, defined as the first and secondary treatment within 60 days after the first treatment, were selected and classified into three initial treatment groups: LRT, sorafenib, and no treatment. Results Among 3,401 BCLC C HCC patients, 1,486 were included in the study and the remaining patients were excluded as they did not meet the criteria (eg, underwent local treatments without radiotherapy [RT] or received chemotherapy other than sorafenib). Of these, 266 were assigned to LRT (17.9%), 316 to sorafenib (21.3%), and 904 to no treatment group (60.8%). Median survival time of the sorafenib group was shorter than that of the LRT group (3.8 vs 7.6 months, P<0.001). In multivariable analysis, sorafenib group showed significantly higher risk related to mortality compared to LRT group, not only among all patients (HR: 1.50, 95% CI: 1.23-1.84) but also between subgroup cohorts with portal invasions (1.55, 1.23-1.84), with lymph node metastases (2.42, 1.53-3.83), without distant metastases (1.43, 1.10-1.87), and with distant metastases (1.57, 1.13-2.19). Additionally, no treatment group showed the worst survival among the three treatment groups not only in all patients, but also in all subgroups of patients (P<0.001 in all). Conclusion LRT as an initial treatment showed survival benefit as compared to sorafenib in HCC patients of BCLC C.
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Affiliation(s)
- Jeongshim Lee
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Radiation Oncology, Inha University Hospital, Incheon, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Republic of Korea,
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Ansan, Republic of Korea,
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Arcangeli S, Jereczek-Fossa BA, Alongi F, Aristei C, Becherini C, Belgioia L, Buglione M, Caravatta L, D'Angelillo RM, Filippi AR, Fiore M, Genovesi D, Greco C, Livi L, Magrini SM, Marvaso G, Mazzola R, Meattini I, Merlotti A, Palumbo I, Pergolizzi S, Ramella S, Ricardi U, Russi E, Trovò M, Sindoni A, Valentini V, Corvò R. Combination of novel systemic agents and radiotherapy for solid tumors - part I: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment efficacy. Crit Rev Oncol Hematol 2019; 134:87-103. [PMID: 30658886 DOI: 10.1016/j.critrevonc.2018.11.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 11/13/2018] [Accepted: 11/20/2018] [Indexed: 02/07/2023] Open
Abstract
Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.
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Affiliation(s)
- Stefano Arcangeli
- Department of Radiation Oncology, Policlinico S. Gerardo and University of Milan "Bicocca", Milan, Italy.
| | | | - Filippo Alongi
- Department of Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, and University of Brescia, Brescia, Italy
| | - Cynthia Aristei
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Perugia General Hospital, Perugia, Italy
| | - Carlotta Becherini
- Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy
| | - Liliana Belgioia
- Department of Radiation Oncology, Ospedale Policlinico San Martino and University of Genoa, Genoa, Italy
| | - Michela Buglione
- Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy
| | - Luciana Caravatta
- Department of Radiation Oncology, SS. Annunziata Hospital, G. D'Annunzio University of Chieti, Chieti, Italy
| | | | | | - Michele Fiore
- Radiotherapy Unit, Campus Bio-Medico University, Rome, Italy
| | - Domenico Genovesi
- Department of Radiation Oncology, SS. Annunziata Hospital, G. D'Annunzio University of Chieti, Chieti, Italy
| | - Carlo Greco
- Radiotherapy Unit, Campus Bio-Medico University, Rome, Italy
| | - Lorenzo Livi
- Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy
| | - Stefano Maria Magrini
- Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy
| | - Giulia Marvaso
- Deparment of Radiation Oncology of IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Rosario Mazzola
- Department of Radiation Oncology, Sacro Cuore Don Calabria Cancer Care Center, Negrar-Verona, and University of Brescia, Brescia, Italy
| | - Icro Meattini
- Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Firenze, Italy
| | - Anna Merlotti
- Department of Radiation Oncology, S. Croce and Carle Teaching Hospital, Cuneo, Italy
| | - Isabella Palumbo
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Perugia General Hospital, Perugia, Italy
| | - Stefano Pergolizzi
- Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Italy
| | - Sara Ramella
- Radiotherapy Unit, Campus Bio-Medico University, Rome, Italy
| | | | - Elvio Russi
- Department of Radiation Oncology, S. Croce and Carle Teaching Hospital, Cuneo, Italy
| | - Marco Trovò
- Department of Radiation Oncology, Azienda Sanitaria Universitaria Integrata of Udine, Udine, Italy
| | - Alessandro Sindoni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Vincenzo Valentini
- Gemelli Advanced Radiation Therapy Center, Fondazione Policlinico Universitario "A. Gemelli", Catholic University of Sacred Heart, Rome, Italy
| | - Renzo Corvò
- Department of Radiation Oncology, Ospedale Policlinico San Martino and University of Genoa, Genoa, Italy
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Yuan Z, Wang Y, Hu C, Gao W, Zheng J, Li W. Efficacy of Percutaneous Thermal Ablation Combined With Transarterial Embolization for Recurrent Hepatocellular Carcinoma After Hepatectomy and a Prognostic Nomogram to Predict Survival. Technol Cancer Res Treat 2019; 17:1533033818801362. [PMID: 30244651 PMCID: PMC6153531 DOI: 10.1177/1533033818801362] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
AIM This study aimed to evaluate the efficacy of percutaneous thermal ablation combined with transarterial embolization for recurrent hepatocellular carcinoma after hepatectomy and establish a prognostic nomogram to predict survival. METHODS One hundred seventeen patients with recurrent hepatocellular carcinoma receiving ablation from 2009 to 2014 were included in primary cohort to establish a prognostic nomogram. Between 2014 and 2016, 51 patients with recurrent hepatocellular carcinoma treated by ablation were enrolled in the validation cohort to validate the predictive accuracy of the nomogram. All patients underwent locoregional ablation. Overall survival was the primary end point, and progression-free survival was the second end point. The performance of the nomogram was assessed through concordance index and calibration curve and compared with 5 conventional hepatocellular carcinoma staging systems. RESULTS The 1-, 3-, and 5-year overall survival rates of primary cohort were 88.4%, 70.7%, and 64.1%, respectively. The 1-, 3-, and 5-year progression-free survival rates of primary cohort were 44%, 14%, and 8.7%, respectively. The results of multivariate analysis showed that tumor size ( P = .0469; hazard ratio, 1.020; 95% confidence interval, 1.0004-1.040), preoperative extrahepatic disease ( P = .0675; hazard ratio, 2.604; 95% confidence interval, 0.933-7.264), and close to hepatic hilum <2 cm ( P = .0053; hazard ratio, 3.691; 95% confidence interval, 1.474-9.240) were predictive factors for overall survival. The study established a nomogram to predict survival (concordance index, 0.752; 95% confidence interval, 0.656-0.849). According to the predicted overall survival, patients with recurrent hepatocellular carcinoma were divided into 3 risk classes ( P < .05): low-risk group (total score <55; predicted 5-year overall survival rate, 82.9%), intermediate-risk group (55 ≤ total score < 99; predicted 5-year overall survival rate, 52.8%), and high-risk group (hazard ratio, total score ≥99; predicted 5-year overall survival rate, not available). CONCLUSION Percutaneous thermal ablation appears to be an effective procedure for the treatment of recurrent hepatocellular carcinoma after hepatectomy. The proposed nomogram provides a mechanism to accurately predict survival and could stratify risk among patients with recurrent hepatocellular carcinoma treated by ablation therapy.
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Affiliation(s)
- Zhuhui Yuan
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Yang Wang
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Caixia Hu
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.,Zhuhui Yuan, Yang Wang, and Caixia Hu contributed equally to this work
| | - Wenfeng Gao
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Jiasheng Zheng
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
| | - Wei Li
- 1 Center of Interventional Oncology and Liver Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China
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Lo YC, Hsu FC, Hung SK, Tseng KC, Hsieh YH, Lee MS, Tseng CW, Lin HY, Chen LC, Chiou WY. Prognosticators of hepatocellular carcinoma with intrahepatic vascular invasion. Tzu Chi Med J 2019; 31:40-46. [PMID: 30692831 PMCID: PMC6334563 DOI: 10.4103/tcmj.tcmj_14_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 10/05/2017] [Accepted: 11/08/2017] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE The prognosis of intrahepatic vascular invasion, including unilateral or main portal vein tumor thrombosis (PVTT) and hepatic vein thrombosis, is still poor. Many patients with intrahepatic vascular invasions never receive radiotherapy (RT). In recent years, more conformal RT techniques such as intensity-modulated RT (IMRT) have been developed and applied to treat other cancers and have significantly improved treatment results and decreased side effects. The purpose of this study is to evaluate the treatment results in patients with intrahepatic vascular invasion and explore the role of IMRT in these treatments. MATERIALS AND METHODS There were a total of 73 patients with newly diagnosed AJCC stage IIIB hepatocellular carcinoma (HCC), with either PVTT or hepatic vein tumor thrombosis between 2007 and 2015 in our hospital. IMRT was used for all patients who received RT. Prognostic factors, including treatment modalities, liver function, and comorbidities, were analyzed using univariate and multivariate analysis with the Cox model. Survival time was analyzed using the Kaplan-Meier method. RESULTS The longest follow-up time was 45.3 months. The median age was 67 years. Univariate analyses indicated that IMRT, transarterial chemoembolization (TACE), target therapy (sorafenib), tumor size, Child-Pugh class, and ascites were significantly associated with overall survival (OS). In multivariate analysis, IMRT (hazard ratio [HR], 0.495; P = 0.019), sorafenib (HR, 0.340; P = 0.013), tumor size (HR, 2.085; P = 0.020), and Child-Pugh class (P = 0.004), were independent prognostic predictors for patients with intrahepatic vessel invasion, but TACE and ascites were not. The outcomes of patients who had different treatment modalities were significantly different (P < 0.001). Patients who received IMRT with TACE had the best outcomes. Patients who received an RT dose above 5400 cGy had better outcomes than those who with a dose below 5400 cGy, although the results were not significantly different (P = 0.248). CONCLUSION IMRT is an important treatment component for patients with intrahepatic vascular invasion. Combined treatment modalities, such as IMRT with TACE, could improve the outcomes of HCC patients with intrahepatic vessel invasion.
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Affiliation(s)
- Yuan-Chen Lo
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Feng-Chun Hsu
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Shih-Kai Hung
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Kuo-Chih Tseng
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Yu-His Hsieh
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Moon-Sing Lee
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Wei Tseng
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hon-Yi Lin
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Liang-Cheng Chen
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Wen-Yen Chiou
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Abstract
For patients with unresectable or medically inoperable hepatocellular carcinoma, there are many local and regional therapies available, including stereotactic body radiotherapy, radiofrequency ablation, and transcatheter embolic approaches. This article will describe these treatment options and review the current comparative literature, suggesting that stereotactic body radiotherapy provides similar or better tumor control and a favorable side effect profile.
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Affiliation(s)
- Yao Yu
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA
| | - Mary Feng
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA.
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Predictive factors of benefit from iodine-125 brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis. Brachytherapy 2018; 18:233-239. [PMID: 30467014 DOI: 10.1016/j.brachy.2018.10.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 09/05/2018] [Accepted: 10/01/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE The aims of this study were to evaluate treatment responses and predictive factors for overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) treated with iodine-125 (125I) brachytherapy. METHODS AND MATERIALS Seventy-seven HCC patients with PVTT underwent 125I brachytherapy after transcatheter arterial chemoembolization. Clinical, laboratory, and radiological evaluation were performed before and after treatment, as well as at 4-6 weeks intervals for 7 years to assess the efficacy and toxicity of therapy. Treatment response was assessed using modified response evaluation criteria in solid tumors. OS and predictive factors for each subgroup were evaluated after treatment. RESULTS In total, 11 patients (14.29%) achieved complete response, and 41 patients (53.25%) achieved partial response. The response rate (complete response + partial response) was 67.53% (52/77). The median OS was 9 months. The multivariable Cox regression model indicated that post-treatment tumor size with PVTT (p = 0.016, hazard ratio [HR] = 1.889, 95% confidence interval [CI]: 1.127 to 3.166) and baseline hemoglobin (p = 0.013, HR=0.518, 95% CI: 0.308 to 0.872) and alkaline phosphatase (p = 0.002, HR=2.275, 95% CI: 1.338 to 3.868) levels were significant independent predictors of OS. CONCLUSIONS 125I brachytherapy results in favorable treatment responses in HCC patients with PVTT. Notably, post-treatment tumor size and baseline hemoglobin and alkaline phosphatase levels are significant independent predictive factors for OS and provide the most predictive information regarding OS.
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Yoo GS, Yu JI, Park HC. Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives. World J Gastroenterol 2018; 24:3090-3100. [PMID: 30065555 PMCID: PMC6064962 DOI: 10.3748/wjg.v24.i28.3090] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/28/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, as few patients can be treated with currently available curative local modalities. In patients with HCC where curative modalities are not feasible, radiation therapy (RT) has emerged as an alternative or combination therapy. With the development of various technologies, RT has been increasingly used for the management of HCC. Among these advances, proton beam therapy (PBT) has several unique physical properties that give it a finite range in a distal direction, and thus no exit dose along the beam path. Therefore, PBT has dosimetric advantages compared with X-ray therapy for the treatment of HCC. Indeed, various reports in the literature have described the favorable clinical outcomes and improved safety of PBT for HCC patients compared with X-ray therapy. However, there are some technical issues regarding the use of PBT in HCC, including uncertainty of organ motion and inaccuracy during calculation of tissue density and beam range, all of which may reduce the robustness of a PBT treatment plan. In this review, we discuss the physical properties, current clinical data, technical issues, and future perspectives on PBT for the treatment of HCC.
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Affiliation(s)
- Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
- Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea
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Li X, Guo W, Guo L, Lau WY, Ge N, Wang K, Cheng S. Should transarterial chemoembolization be given before or after intensity-modulated radiotherapy to treat patients with hepatocellular carcinoma with portal vein tumor thrombus? a propensity score matching study. Oncotarget 2018; 9:24537-24547. [PMID: 29849959 PMCID: PMC5966265 DOI: 10.18632/oncotarget.25224] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 04/06/2018] [Indexed: 02/07/2023] Open
Abstract
Background and Objective To compare the survival outcomes of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who received transarterial chemoembolization (TACE) before or after intensity-modulated radiotherapy (IMRT). Methods During the study period, the survival outcomes of HCC patients with PVTT who underwent TACE before (TACE-RT) or after IMRT (RT-TACE) were compared. Using propensity score matching (PSM), matched pairs of patients were compared. Results There were 76 patients in the TACE-RT group and 36 patients in the RT-TACE group. Using a 2:1 matching, 75 patients were included into this study after PSM: 50 patients in the TACE-RT group and 25 patients in the RT-TACE group. Before PSM, patients in the RT-TACE group showed significantly better survival when compared with the TACE-RT group (median survival, 13.2 months vs.7.4 months; P = 0.014) for patients with main trunk PVTT, and after PSM, the corresponding median survival was 13.2 months vs.7.4 months (P = 0.020). When compared with TACE-RT, RT-TACE had a significantly lower rate of worsening in liver function (9.5% vs. 33.3%, P = 0.044) for patients with main trunk PVTT. Conclusions For HCC patients with main trunk PVTT, IMRT followed by TACE yielded better survival outcomes and liver function when compared to TACE followed by IMRT.
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Affiliation(s)
- Xiaolong Li
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.,Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weixing Guo
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Lei Guo
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wan Yee Lau
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Naijian Ge
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Kang Wang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Shuqun Cheng
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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31
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Child-Pugh Score Maintenance in Cirrhotic Hepatocellular Carcinoma Patients after Radiotherapy: Aspects of Gastroduodenal Complications. TUMORI JOURNAL 2018. [DOI: 10.1177/1778.19270] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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32
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Na SK, Yim SY, Suh SJ, Jung YK, Kim JH, Seo YS, Yim HJ, Yeon JE, Byun KS, Um SH. ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma. J Surg Oncol 2018; 117:912-921. [PMID: 29448306 DOI: 10.1002/jso.24992] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 01/02/2018] [Indexed: 01/27/2023]
Abstract
BACKGROUND The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated. METHODS Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments. RESULTS The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade]). CONCLUSIONS ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC.
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Affiliation(s)
- Seong K Na
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea.,Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Sun Y Yim
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Sang J Suh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Young K Jung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Ji H Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Yeon S Seo
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
| | - Hyung J Yim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Jong E Yeon
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Kwan S Byun
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
| | - Soon H Um
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
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Zhang ZH, Liu QX, Zhang W, Ma JQ, Wang JH, Luo JJ, Liu LX, Yan ZP. Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus. World J Gastroenterol 2017; 23:7735-7745. [PMID: 29209114 PMCID: PMC5703933 DOI: 10.3748/wjg.v23.i43.7735] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Revised: 09/18/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT).
METHODS This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and MPVTT. The patients received either EVBT with stent placement, TACE, and sorafenib (group A, n = 37), or TACE with sorafenib (group B, n = 31). The time to progression (TTP) and overall survival (OS) were evaluated by propensity score analysis.
RESULTS In the entire cohort, the 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A, and 45.8%, 0%, and 0% in group B, respectively (P < 0.001). The median TTP and OS were significantly longer in group A than group B (TTP: 9.0 mo vs 3.4 mo, P < 0.001; OS: 12.3 mo vs 5.2 mo, P < 0.001). In the propensity score-matched cohort, the median OS was longer in group A than in group B (10.3 mo vs 6.0 mo, P < 0.001). Similarly, the median TTP was longer in group A than in group B (9.0 mo vs 3.4 mo, P < 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement, TACE, and sorafenib strategy was an independent predictor of favorable OS (HR = 0.18, P < 0.001).
CONCLUSION EVBT combined with stent placement, TACE, and sorafenib might be a safe and effective palliative treatment option for MPVTT.
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Affiliation(s)
- Zi-Han Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Qing-Xin Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Wen Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Jing-Qin Ma
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Jian-Hua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Jian-Jun Luo
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Ling-Xiao Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
| | - Zhi-Ping Yan
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University and Shanghai Institute of Medical Imaging, Shanghai 20032, China
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Son SH, Park EY, Park HH, Kay CS, Jang HS. Pre-radiotherapy neutrophil-to-lymphocyte ratio as an independent prognostic factor in patients with locally advanced hepatocellular carcinoma treated with radiotherapy. Oncotarget 2017; 8:16964-16971. [PMID: 28199977 PMCID: PMC5370014 DOI: 10.18632/oncotarget.15209] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 01/27/2017] [Indexed: 12/16/2022] Open
Abstract
We aimed to investigate the pre-radiotherapy neutrophil-to-lymphocyte ratio (prNLR) as a prognostic factor in patients with locally advanced hepatocellular carcinoma (HCC) treated with radiotherapy (RT), and to determine the optimal cut-off value for prNLR. We retrospectively evaluated 56 patients with locally advanced HCC treated with RT (helical tomotherapy) between March 2006 and February 2012. The optimal cut-off value was determined by using a maximally selected log-rank test. Prognostic factors that influence the local progression-free survival (PFS) and overall survival (OS) were evaluated. A prNLR of 2.1 was determined to be the optimal cut-off value. In a comparison between the high-prNLR group and the low-prNLR group, there was a 13.1-month difference in the median OS (10.3 vs. 23.4 months, p = 0.003) and a 10.4-month difference in the median local PFS (7.1 vs. 17.5 months, p = 0.001). On multivariate analysis of prognostic factors for local PFS and OS, the prNLR was identified as an independent prognostic factor, and the hazard ratio was 4.2 and 2.5, respectively. We demonstrated that a low prNLR was significantly associated with better PFS and OS in patients with locally advanced HCC treated with RT, and the prNLR should be considered as an independent prognostic factor in these patients.
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Affiliation(s)
- Seok Hyun Son
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Young Park
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Hyun Park
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Seung Kay
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Galle PR, Tovoli F, Foerster F, Wörns MA, Cucchetti A, Bolondi L. The treatment of intermediate stage tumours beyond TACE: From surgery to systemic therapy. J Hepatol 2017; 67:173-183. [PMID: 28323121 DOI: 10.1016/j.jhep.2017.03.007] [Citation(s) in RCA: 178] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
Treatment of hepatocellular carcinoma (HCC) is dependent on the stage of the disease. Intermediate stage HCC encompasses the largest subgroup of patients with the disease, and is characterized by substantial heterogeneity. The standard therapeutic approach, transarterial chemoembolization (TACE), is probably over-used and may not be appropriate for all patients with intermediate stage HCC. In patients with extensive tumour bulk, multi-nodular spread or impaired liver function, TACE may not be optimal and other treatments can be considered as a first-line treatment. These include surgery, percutaneous ablation, radioembolization or systemic treatment. In addition, patients who do not achieve complete or partial necrosis (TACE failure) and patients with early recurrence after TACE, should be managed individually, considering systemic treatments usually reserved for advanced disease. In selected cases and in patients who achieve downstaging, radical approaches such as hepatic resection or even liver transplantation can be considered. In this review, we evaluate the current literature for the treatment strategies for patients with intermediate Barcelona Clinic Liver Cancer (BCLC) B stage HCC.
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Affiliation(s)
- Peter R Galle
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany.
| | - Francesco Tovoli
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Friedrich Foerster
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Marcus A Wörns
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Alessandro Cucchetti
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Chirurgia generale e Trapianti, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Luigi Bolondi
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
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36
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Song JE, Jung KS, Kim DY, Song K, Won JY, Lee HW, Kim BK, Kim SU, Park JY, Ahn SH, Seong J, Han KH. Transarterial Radioembolization Versus Concurrent Chemoradiation Therapy for Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis. Int J Radiat Oncol Biol Phys 2017; 99:396-406. [PMID: 28871990 DOI: 10.1016/j.ijrobp.2017.05.049] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 05/13/2017] [Accepted: 05/30/2017] [Indexed: 01/01/2023]
Abstract
PURPOSE It is unclear whether the efficacy and safety of concurrent chemoradiation therapy (CCRT) and transarterial radioembolization (TARE) with 90Y are comparable in patients with locally advanced hepatocellular carcinoma. METHODS AND MATERIALS In total, 209 treatment-naive patients with stage B or C cancer according to the Barcelona Clinic Liver Cancer classification who were treated with TARE or CCRT were analyzed. Propensity scores were calculated and matched at a 1:1 ratio for TARE versus CCRT using age, tumor size, tumor number, portal vein thrombosis, and Barcelona Clinic Liver Cancer staging. In the CCRT group, concurrent hepatic arterial infusion chemotherapy with 5-fluorouracil was delivered at a dosage of 500 mg/d during the first and last 5 days of radiation therapy (median, 45 Gy). Overall survival, freedom from progression, tumor response, and complication rate were compared between the TARE and CCRT groups. RESULTS Among 209 patients, 124 (62 undergoing TARE and 62 undergoing CCRT) were selected after propensity score matching. Overall survival (TARE vs CCRT, 14.0 months vs 13.2 months, P=.435) and freedom from progression (6.9 months vs 7.8 months, P=.437) were comparable between the 2 groups. Objective response rates at 1 month after treatment were higher for CCRT than for TARE (46.8% vs 16.1%, P<.001), while objective response rates at 3 months were significantly higher for TARE than for CCRT (39.3% vs 21.4%, P=.04). There was no significant difference in long-term response rates (at 6 months and 1 year) between the 2 groups. The CCRT group experienced a higher rate of curative resection or liver transplantation after treatment than the TARE group, although the statistical significance was marginal (24.2% vs 11.3%, P=.060). Treatment-related complications were less frequent after TARE than after CCRT. CONCLUSIONS Both treatments yielded comparable survival rates and long-term response rates in patients with intermediate- or advanced-stage hepatocellular carcinoma. The role of these modalities as a bridge to curative therapy requires further investigation.
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Affiliation(s)
- Jeong Eun Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyu Sik Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Kijun Song
- Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Yun Won
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Kuriyama K. 11. Radiotherapy for Hepatocellular Carcinoma. Nihon Hoshasen Gijutsu Gakkai Zasshi 2017; 73:411-422. [PMID: 28529257 DOI: 10.6009/jjrt.2017_jsrt_73.5.411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Kengo Kuriyama
- Department of Radiology and Radiation Oncology, Faculty of Medicine, University of Yamanashi
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Lock MI, Klein J, Chung HT, Herman JM, Kim EY, Small W, Mayr NA, Lo SS. Strategies to tackle the challenges of external beam radiotherapy for liver tumors. World J Hepatol 2017; 9:645-656. [PMID: 28588749 PMCID: PMC5437609 DOI: 10.4254/wjh.v9.i14.645] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 12/20/2016] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity. Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis. However, the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment, management of motion and appropriate selection of dose regimen. This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines. Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation. Indeed, certain sub-populations, such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization, have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration. Implementing a liver radiation program requires three primary challenges to be addressed: (1) immobilization and motion management; (2) localization; and (3) dose regimen and constraint selection. Strategies to deal with motion include simple internal target volume (ITV) expansions, non-gated ITV reduction strategies, breath hold methods, and surrogate marker methods to enable gating or tracking. Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy, imaging modalities, and margin management. Finally, a dose response has been demonstrated and dose regimens appear to be converging. A more uniform approach to treatment in terms of technique, dose selection and patient selection will allow us to study liver radiation in larger and, hopefully, multicenter randomized studies.
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Tarantino L, Busto G, Nasto A, Fristachi R, Cacace L, Talamo M, Accardo C, Bortone S, Gallo P, Tarantino P, Nasto RA, Di Minno MND, Ambrosino P. Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study. World J Gastroenterol 2017; 23:906-918. [PMID: 28223736 PMCID: PMC5296208 DOI: 10.3748/wjg.v23.i5.906] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2016] [Revised: 11/14/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients.
METHODS Six patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter.
RESULTS Post-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT.
CONCLUSION In patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.
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Liao Y, Zheng Y, He W, Li Q, Shen J, Hong J, Zou R, Qiu J, Li B, Yuan Y. Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence. Oncol Lett 2017; 13:984-992. [PMID: 28356989 PMCID: PMC5351299 DOI: 10.3892/ol.2016.5525] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Accepted: 05/13/2016] [Indexed: 01/27/2023] Open
Abstract
Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.e., those with portal vein tumor thrombosis, adjacent organ involvement or tumor rupture) who underwent resection were analyzed. The patients were categorized into the sorafenib group (n=14) or the best supportive care (BSC) group (n=28). Although the histological grade, Barcelona Clinic Liver Cancer Stage, tumor size, nodule number and proportion of patients with high serum α-fetoprotein levels were comparable between the sorafenib and BSC groups, those receiving sorafenib following resection had significantly longer disease-free survival (DFS) of 5.2 months [95% confidence interval (CI), 1.2-9.2 months] compared with the BSC group [1.8 months (95% CI, 0.6-3.0 months)]. No differences in overall survival were noted between the groups. Furthermore, no drug-related adverse events resulted in discontinuation of sorafenib therapy. Univariate log-rank analysis revealed that sorafenib treatment (P=0.002) and treatment prior to resection (P=0.012) were significantly associated with longer DFS; however, sorafenib therapy (P=0.027) and tumor size (P=0.028) were associated with longer DFS by multivariate analysis. Furthermore, sorafenib was well-tolerated and improved DFS in patients with advanced HCC who underwent hepatic resection. Thus, tumor resection followed by sorafenib therapy may represent an effective therapeutic strategy for patients with advanced HCC. This possibility should be confirmed in larger, multicenter studies.
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Affiliation(s)
- Yadi Liao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Wei He
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Qijiong Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jingxian Shen
- Department of Medical Imaging and Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jian Hong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Ruhai Zou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Binkui Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
- Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
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Jeong Y, Shin MH, Yoon SM, Song GW, Kim KH, Ahn CS, Moon DB, Hwang S, Park JH, Kim JH, Lee SG. Liver Transplantation After Transarterial Chemoembolization and Radiotherapy for Hepatocellular Carcinoma with Vascular Invasion. J Gastrointest Surg 2017; 21:275-283. [PMID: 27778254 DOI: 10.1007/s11605-016-3302-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 10/09/2016] [Indexed: 01/31/2023]
Abstract
PURPOSE The study aims to analyze the oncologic outcomes of living donor liver transplantation (LDLT) after combined transarterial chemoembolization (TACE) and radiotherapy for hepatocellular carcinoma (HCC) with major vascular invasion. METHODS We retrospectively reviewed 17 HCC patients with major vascular invasion who underwent LDLT after combined treatment modality between May 2007 and September 2014. The LDLT timing was determined by the surgeons depending on the disease status and liver function. The intrahepatic recurrence-free survival, disease-free survival (DFS), and overall survival (OS) rates were estimated from the date of the LDLT. RESULTS The median follow-up period was 24.5 months (range, 6.4-66.0 months) after the LDLT. The interval between the combined treatment and the LDLT was a median of 5 months (range, 0.4-65.3 months). On the explanted liver, total necrosis was shown in five patients (29.4 %). The 1- and 3-year DFS rates were 70.6 and 57.8 %, respectively. The 1- and 3-year OS rates were 87.4 and 60.5 %, respectively. The major pattern of failure was distant metastasis (35.3 %), and intrahepatic recurrence occurred in three patients (17.6 %) who experienced distant metastasis. CONCLUSIONS In the selected HCC patients with major vascular invasion, LDLT after combined TACE and radiotherapy showed acceptable oncologic outcomes.
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Affiliation(s)
- Yuri Jeong
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Min-Ho Shin
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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Im JH, Yoon SM, Park HC, Kim JH, Yu JI, Kim TH, Kim JW, Nam TK, Kim K, Jang HS, Kim JH, Kim MS, Yoon WS, Jung I, Seong J. Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area. Liver Int 2017; 37:90-100. [PMID: 27317941 DOI: 10.1111/liv.13191] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Accepted: 06/13/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS This nationwide, multicenter study investigated treatment outcomes as well as the optimal radiotherapeutic strategy in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT). METHODS We retrospectively reviewed the records of 985 patients who received radiotherapy (RT) for PVTT. The median equivalent RT dose was 48.75 Gy. Combined treatment, defined as liver-directed treatments performed within a month of RT, was administered to 657 patients (66.7%). The PVTT and primary tumour were irradiated in 413 patients (41.9%), and PVTT only was targeted in 572 patients (58.1%). RESULTS The response rate of the PVTT was 51.8%, and RT responders had a significantly longer survival than non-responders (15.2 vs. 6.9 months). Equivalent RT dose and combined treatment predicted response of PVTT. The median overall survival (OS) was 10.2 months. Multivariate analysis revealed the equivalent RT dose ˃45 Gy and combined treatment as significant positive factors for OS. In the propensity score matching analysis, the combined treatment group had better OS than the no combined treatment group, whereas the OS of the PVTT + primary tumour group did not differ significantly from that of the PVTT only group. CONCLUSION The equivalent RT dose ˃45 Gy, given in combination with other treatments, provided better PVTT control and OS. The optimal RT volume is suggested for either PVTT + primary or PVTT only. Taken together, multimodal treatment with equivalent RT dose higher than 45 Gy is recommended for patients with HCC and PVTT.
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Affiliation(s)
- Jung Ho Im
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Min Yoon
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Jun Won Kim
- Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Taek-Keun Nam
- Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute Radiological & Medical Sciences, Seoul, Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical Center, Ansan, Korea
| | - Inkyung Jung
- Department of Biostatistics, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Zhao Q, Zhu K, Yue J, Qi Z, Jiang S, Xu X, Feng R, Wang R. Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis. Ther Clin Risk Manag 2016; 13:21-31. [PMID: 28053537 PMCID: PMC5189701 DOI: 10.2147/tcrm.s126181] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Purpose Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment.
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Affiliation(s)
- Qianqian Zhao
- School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences; Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Kunli Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Jinbo Yue
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Zhonghua Qi
- School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences; Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Shumei Jiang
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Xiaoqing Xu
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Rui Feng
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Renben Wang
- Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People's Republic of China
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Portal Vein Stenting Combined with Iodine-125 Seeds Endovascular Implantation Followed by Transcatheter Arterial Chemoembolization for Treatment of Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3048261. [PMID: 27999793 PMCID: PMC5143688 DOI: 10.1155/2016/3048261] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/03/2016] [Indexed: 12/20/2022]
Abstract
Aim was to assess the therapeutic value of portal vein stenting (PVS) combined with iodine-125 seed (125I seed) strand endovascular implantation followed by transcatheter arterial chemoembolization (TACE) for treating patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). This was a retrospective study of 34 patients aged 29–81 years, diagnosed HCC with PVTT, and treated with PVS combined with 125I seed strand endovascular implantation followed by TACE between January 2012 and August 2014. Survival, stent patency, technical success rate, complications related to the procedure, and adverse events were recorded. The technical success rate was 100%. No serious procedure-related adverse event was recorded. The median survival was 147 days. The cumulative survival rates and stent patency rates at 90, 180, and 360 days were 94.1%, 61.8%, and 32.4% and 97.1% (33/34), 76.9% (24/34), and 29.4% (10/34), respectively. PVS combined with 125I seed strand endovascular implantation followed by TACE is feasible for patients with HCC and PVTT. It resulted in appropriate survival and stent patency, with no procedure-related adverse effects.
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Li XL, Guo WX, Hong XD, Yang L, Wang K, Shi J, Li N, Wu MC, Cheng SQ. Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus: A propensity score analysis. Hepatol Res 2016; 46:1088-1098. [PMID: 26783741 DOI: 10.1111/hepr.12657] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2015] [Revised: 01/08/2016] [Accepted: 01/12/2016] [Indexed: 12/16/2022]
Abstract
AIM The survival outcome of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) who received transarterial chemoembolization (TACE) combined with radiotherapy (RT) remains unclear. METHODS A total of 112 and 735 HCC patients with PVTT undergoing TACE combined with RT and TACE alone, respectively, were evaluated. One hundred and eight pairs of matched patients were selected from each treatment arm by using a propensity score matching (PSM) analysis. RESULTS Of the whole study population, TACE combined with RT showed significant survival benefits compared with TACE in all patients (median survival, 11.0 vs 4.8 months; P < 0.001), especially in patients with PVTT involving the right/left portal vein (median survival, 12.5 vs 5.2 months; P < 0.001) and main portal vein trunk (median survival, 8.9 vs 4.3 months; P < 0.001). After one-to-one PSM, 108 pairs of matched patients were selected for further analysis. In the propensity model, the median survival time was 10.9 versus 4.1 months (P < 0.001) in all patients, 12.5 versus 4.4 months (P = 0.002) in patients with PVTT involving the right/left portal vein and 8.9 versus 4.0 months (P < 0.001) in patients with PVTT involving the main portal vein trunk. The treatment, maximum lesion diameter and main trunk PVTT were the independent prognostic factors for survival at uni- and multivariate analysis. CONCLUSION TACE combined with RT provides a significantly better survival outcome than TACE for unresectable HCC patients with PVTT, especially for patients with PVTT involving the right/left portal vein or main trunk.
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Affiliation(s)
- Xiao-Long Li
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Xiao-Dong Hong
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Liang Yang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Kang Wang
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Jie Shi
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Nan Li
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
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Son SH, Jang HS, Sung SY, Kang HJ, Lee S, Kay CS. Identifying the optimal criteria of radiotherapeutic parameters for patients with unresectable locally advanced hepatocellular carcinoma. Oncotarget 2016; 6:42372-9. [PMID: 26510905 PMCID: PMC4747233 DOI: 10.18632/oncotarget.5713] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 10/05/2015] [Indexed: 12/26/2022] Open
Abstract
The purpose of this study is to identify the optimal criteria of the radiotherapeutic parameters in patients with unresectable locally advanced hepatocellular carcinoma (HCC). 103 patients were enrolled in this study. All patients received RT delivered using the TomoTherapy Hi-Art system between March 2006 and February 2012. We evaluated the planning target volume (PTV), total dose (Gy10), and NTNL-V(BED20) (non-target normal liver volume receiving more than a biologically effective dose of 20 Gy8) as significant radiotherapeutic parameters associated with hepatic function deterioration and local progression-free survival (PFS). A PTV of 279 cm3 or 304 cm3, a total dose of 60 Gy10, and a NTNL-V(BED20) of 40.8% were identified as the optimal cut-off values of radiotherapeutic parameters to prevent hepatic function deterioration and prolong local PFS. Based on these findings, patients were divided in a favorable and an unfavorable prognosis group. The differences in median local PFS, overall survival, and incidence of deteriorated hepatic function between the two groups were 11.2 months, 11.1 months, and 71.7%, respectively (p < 0.001 in each case). In conclusion, we suggest that the optimal criteria of the radiotherapeutic parameters for patients with unresectable locally advanced HCC are: PTV ≤ 279 cm3, total dose > 60 Gy10, and NTNL-V(BED20) ≤ 40.8%.
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Affiliation(s)
- Seok Hyun Son
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Soo Yoon Sung
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hye Jin Kang
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sojung Lee
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chul Seung Kay
- Department of Radiation Oncology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Iodine-125 implantation plus transarterial chemoembolization for the treatment of hepatocellular carcinoma of 3-5cm: A propensity score matching study. Dig Liver Dis 2016; 48:1082-7. [PMID: 27365224 DOI: 10.1016/j.dld.2016.06.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 05/19/2016] [Accepted: 06/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Both iodine-125 implantation and transarterial chemoembolization (TACE) are feasible options for hepatocellular carcinoma (HCC). The aim of the research is to investigate whether iodine-125 implantation combined with TACE could improve the overall survival of patients with HCC of 3-5cm. METHODS 144 patients with HCC of 3-5cm who underwent iodine-125 implantation plus TACE and TACE alone were retrospectively enrolled in this study. To reduce the selection bias, 55 matched pairs of patients were generated by propensity score matching (PSM). Their overall survival was compared by the Kaplan-Meier method. Independent prognostic factors were identified by Cox proportional hazards regression model. RESULTS patients receiving iodine-125 implantation plus TACE have significantly better overall survival than patients receiving TACE alone (P<0.001). After PSM, treatment of iodine-125 plus TACE still provide better survival (1-year, 89.1% vs. 65.5%; 3-year, 51.0% vs. 7.4%; P<0.001). In multivariate analysis, BCLC stage, vascular invasion and treatment modality independently predicted the prognosis. No severe adverse events occurred in both groups. CONCLUSION for HCC patients of 3-5cm for whom surgical intervention is not an option, iodine-125 implantation combined with TACE might be an effective and viable alternative to provide better overall survival.
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Matsuo Y, Yoshida K, Nishimura H, Ejima Y, Miyawaki D, Uezono H, Ishihara T, Mayahara H, Fukumoto T, Ku Y, Yamaguchi M, Sugimoto K, Sasaki R. Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy. JOURNAL OF RADIATION RESEARCH 2016; 57:512-523. [PMID: 27053259 PMCID: PMC5045071 DOI: 10.1093/jrr/rrw028] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 02/11/2016] [Indexed: 05/12/2023]
Abstract
This study aimed to evaluate the efficacy of stereotactic body radiotherapy (SBRT) compared with three-dimensional conformal radiotherapy (3DCRT). Forty-three patients with portal vein tumor thrombosis (PVTT)/inferior vena cava tumor thrombosis (IVCTT) treated with SBRT (27 with CyberKnife (CK) and 16 with TrueBeam (TB)) from April 2013 to December 2014, and 54 treated with 3DCRT from June 2008 to March 2013 were evaluated. Dosimetric parameters, response to radiotherapy (RT) and survival outcomes were compared in total SBRT vs. 3DCRT, CK vs. 3DCRT and TB vs. 3DCRT, respectively. The median biologically effective dose 10 (BED10) values in total SBRT, CK, TB and 3DCRT were 73.4 Gy10, 75.0 Gy10, 60.5 Gy10 and 58.5 Gy10, respectively (P < 0.001 in total SBRT vs. 3DCRT, P < 0.001 in CK vs. 3DCRT, P = 0.004 in TB vs. 3DCRT). The tumor response rates were 67%, 70%, 62% and 46%, respectively (P = 0.04, P = 0.04, P = 0.25). The 1-year overall survival rates were 49.3%, 56.7%, 38.1% and 29.3%, respectively (P = 0.02, P = 0.02, P = 0.30), and the 1-year local progression rates were 20.4%, 21.9%, 18.8% and 43.6%, respectively (P = 0.01, P = 0.04, P = 0.10). The use of SBRT made it possible to achieve a higher BED10 compared with the use of 3DCRT. Improvements in local control and survival were achieved in the CK group and the total SBRT group. Our results suggest that SBRT may have the potential to be the standard RT technique for the treatment of PVTT/IVCTT.
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Affiliation(s)
- Yoshiro Matsuo
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Kenji Yoshida
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Hideki Nishimura
- Department of Radiation Oncology, Kobe Minimally Invasive Cancer Center, 8-5-1, Minatojima-Nakamachi, Chuou-Ku, Kobe, Hyogo 650-0046, Japan
| | - Yasuo Ejima
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Daisuke Miyawaki
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Haruka Uezono
- Department of Radiation Oncology, Kobe Minimally Invasive Cancer Center, 8-5-1, Minatojima-Nakamachi, Chuou-Ku, Kobe, Hyogo 650-0046, Japan
| | - Takeaki Ishihara
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Hiroshi Mayahara
- Department of Radiation Oncology, Kobe Minimally Invasive Cancer Center, 8-5-1, Minatojima-Nakamachi, Chuou-Ku, Kobe, Hyogo 650-0046, Japan
| | - Takumi Fukumoto
- Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Yonson Ku
- Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Masato Yamaguchi
- Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Koji Sugimoto
- Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
| | - Ryohei Sasaki
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-Cho, Chuou-Ku, Kobe, Hyogo 650-0017, Japan
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Chan SL, Chong CCN, Chan AWH, Poon DMC, Chok KSH. Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016. World J Gastroenterol 2016; 22:7289-7300. [PMID: 27621575 PMCID: PMC4997643 DOI: 10.3748/wjg.v22.i32.7289] [Citation(s) in RCA: 129] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/27/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Portal vein tumor thrombosis (PVTT) is a common phenomenon in hepatocellular carcinoma (HCC). Compared to HCC without PVTT, HCC with PVTT is characterized by an aggressive disease course, worse hepatic function, a higher chance of complications related to portal hypertension and poorer tolerance to treatment. Conventionally, HCC with PVTT is grouped together with metastatic HCC during the planning of its management, and most patients are offered palliative treatment with sorafenib or other systemic agents. As a result, most data on the management of HCC with PVTT comes from subgroup analyses or retrospective series. In the past few years, there have been several updates on management of HCC with PVTT. First, it is evident that HCC with PVTT consists of heterogeneous subgroups with different prognoses. Different classifications have been proposed to stage the degree of portal vein invasion/thrombosis, suggesting that different treatment modalities may be individualized to patients with different risks. Second, more studies indicate that more aggressive treatment, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. In this review, we aim to discuss the recent conceptual changes and summarize the data on the management of HCC with PVTT.
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Park SH, Kim JC, Kang MK. Technical advances in external radiotherapy for hepatocellular carcinoma. World J Gastroenterol 2016; 22:7311-7321. [PMID: 27621577 PMCID: PMC4997637 DOI: 10.3748/wjg.v22.i32.7311] [Citation(s) in RCA: 16] [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: 03/29/2016] [Revised: 06/21/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023] Open
Abstract
Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.
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