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Tadokoro T, Tani J, Morishita A, Fujita K, Masaki T, Kobara H. The Treatment of Hepatocellular Carcinoma with Major Vascular Invasion. Cancers (Basel) 2024; 16:2534. [PMID: 39061174 PMCID: PMC11274937 DOI: 10.3390/cancers16142534] [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: 06/29/2024] [Revised: 07/10/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion.
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Affiliation(s)
| | | | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Takamatsu 761-0793, Kagawa, Japan; (T.T.); (J.T.); (K.F.); (T.M.); (H.K.)
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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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Narita H, Kawaratani H, Shibamoto A, Takeda S, Ozutsumi T, Tsuji Y, Fujinaga Y, Kitagawa K, Nishimura N, Hokuto D, Sho M, Yoshiji H. Long-term survival with sorafenib-based multidisciplinary treatment for Vp4 hepatocellular carcinoma: a case report. Clin J Gastroenterol 2022; 15:953-959. [PMID: 35773571 DOI: 10.1007/s12328-022-01667-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 06/20/2022] [Indexed: 02/07/2023]
Abstract
The prognosis of highly advanced unresectable hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT) is poor. There are currently no reports of long-term survival for up to 5 years in patients with advanced HCC who were treated with sorafenib. We describe a patient with Vp4 HCC who was treated with a sorafenib-based multidisciplinary treatment and experienced long-term survival, which may be the longest survival to date. A man in his late 60 s presented with general fatigue. Eight years previously, he received interferon monotherapy for chronic hepatitis C for 48 weeks and achieved a sustained virological response. He was diagnosed with a PVTT (Vp4) with diffuse-type HCC in the S6 lobe of the liver. He received hepatic arterial infusion of chemotherapy using 5-fluorouracil and cisplatin. Because of the occurrence of adverse effects, he was placed on sorafenib treatment. The treatment was effective and the HCC reduced. However, after 3 years of treatment, a 2-cm HCC was observed in the S5 lobe, and the patient underwent laparoscopic partial hepatectomy. After the operation, he continued to receive sorafenib, with no obvious recurrence, and survived for over 108 months after the first treatment. There are currently no reported cases of long-term progression-free survival by sorafenib for five years in patients of Vp4 HCC. In conclusion, we report a case of longest survival of a patient with Vp4 HCC treated with sorafenib-based multidisciplinary treatment.
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Affiliation(s)
- Hibiki Narita
- Clinical Training Center, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Hideto Kawaratani
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan.
| | - Akihiko Shibamoto
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Soichi Takeda
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Takahiro Ozutsumi
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Yuki Tsuji
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Yukihisa Fujinaga
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Koh Kitagawa
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Norihisa Nishimura
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, Kashihara, Nara, 634-8522, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology and Metabolism, Nara Medical University, Kashihara, Nara, 634-8522, Japan
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Kimura T, Fujiwara T, Kameoka T, Adachi Y, Kariya S. The Current Role of Stereotactic Body Radiation Therapy (SBRT) in Hepatocellular Carcinoma (HCC). Cancers (Basel) 2022; 14:cancers14184383. [PMID: 36139545 PMCID: PMC9496682 DOI: 10.3390/cancers14184383] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 09/06/2022] [Accepted: 09/06/2022] [Indexed: 11/16/2022] Open
Abstract
The role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to pre-transplantation and the treatment of oligometastases from HCC in combination with immune checkpoint inhibitors (ICI). In early-stage HCC, many promising prospective results of SBRT have been reported, although SBRT is not usually indicated as a first treatment potion in localized HCC according to several guidelines. In the treatment of portal vein or inferior vena cava tumor thrombi, several reports using various dose-fraction schedules have shown relatively good response rates with low toxicities and improved survival due to the rapid advancements in systemic therapy. Although SBRT is regarded as a substitute therapy when conventional bridging therapies to transplantation, such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), are not applicable or fail in controlling tumors, SBRT may offer advantages in patients with borderline liver function who may not tolerate TACE or RFA, according to several reports. For oligometastases, the combination of SBRT with ICI could potentially induce an abscopal effect in patients with HCC, which is expected to provide the rationale for SBRT in the treatment of oligometastatic disease in the near future.
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Affiliation(s)
- Tomoki Kimura
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nangoku-shi 783-8505, Kochi, Japan
- Correspondence:
| | - Toshiki Fujiwara
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nangoku-shi 783-8505, Kochi, Japan
| | - Tsubasa Kameoka
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nangoku-shi 783-8505, Kochi, Japan
| | - Yoshinori Adachi
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nangoku-shi 783-8505, Kochi, Japan
- Department of Radiation Oncology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, 1-9-6 Sendamachi, Naka-ku, Hiroshima 730-8619, Hiroshima, Japan
| | - Shinji Kariya
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nangoku-shi 783-8505, Kochi, Japan
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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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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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Chen CT, Liu TH, Shao YY, Liu KL, Liang PC, Lin ZZ. Revisiting Hepatic Artery Infusion Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma. Int J Mol Sci 2021; 22:12880. [PMID: 34884684 PMCID: PMC8657421 DOI: 10.3390/ijms222312880] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/25/2021] [Accepted: 11/25/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results. We propose that future trials of HAIC standardize these key factors to reveal the clinical value of HAIC-based treatments for HCC.
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Affiliation(s)
- Ching-Tso Chen
- Department of Oncology, National Taiwan University Hospital Hsinchu Branch, Hsinchu 300195, Taiwan;
- Department of Oncology, National Taiwan University Hospital, Taipei 100225, Taiwan; (T.-H.L.); (Y.-Y.S.)
| | - Tsung-Hao Liu
- Department of Oncology, National Taiwan University Hospital, Taipei 100225, Taiwan; (T.-H.L.); (Y.-Y.S.)
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
| | - Yu-Yun Shao
- Department of Oncology, National Taiwan University Hospital, Taipei 100225, Taiwan; (T.-H.L.); (Y.-Y.S.)
- Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
| | - Kao-Lang Liu
- Department of Medical Imaging, National Taiwan University Hospital, Taipei 100225, Taiwan;
- Department of Medical Imaging, National Taiwan University Cancer Center, Taipei 106328, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital, Taipei 100225, Taiwan;
- Department of Medical Imaging, National Taiwan University Hospital Hsinchu Branch, Hsinchu 300195, Taiwan
| | - Zhong-Zhe Lin
- Department of Oncology, National Taiwan University Hospital, Taipei 100225, Taiwan; (T.-H.L.); (Y.-Y.S.)
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
- Department of Medical Oncology, National Taiwan University Cancer Center, Taipei 106328, Taiwan
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Khan AR, Wei X, Xu X. Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma - The Changing Tides. J Hepatocell Carcinoma 2021; 8:1089-1115. [PMID: 34522691 PMCID: PMC8434852 DOI: 10.2147/jhc.s318070] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022] Open
Abstract
Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged LFT), and poor performance status of patients. The Barcelona Clinic Liver Cancer staging system places HCC patients with PVTT in advanced stage (BCLC Stage-C). This group contains a fairly heterogeneous patient population, previously considered candidates for palliative systemic therapy with sorafenib. However, this provided modest overall survival (OS) benefit. The results of a recent Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib proved to be non-inferior against sorafenib in a phase III (REFLECT trial), regorafenib (RESORCE trial), ramucirumab (REACH-2), and cabozantinib (CELESTIAL) have been approved second-line therapy in phase III clinical trials. Recently, the data on the prospect of other modalities in the management of HCC with PVTT is mounting with favorable results. Targeting multiple pathways in the HCC cascade using a combination of drugs and other modalities such as RT, TACE, TARE, and HAIC appear effective for systemic and loco-regional control. The quest for the ideal combination therapy and the sequence set is still widely unanswered and prospective trials are lacking. With the armament of available therapeutic options and the advances and refinements in the delivery system, down-staging patients to make them eligible for curative resection has been reported. In a rapidly evolving treatment landscape, performing surgery when appropriate, in the form of LR and even LT to achieve cure does not seem farfetched. Likewise, adjuvant therapy and prompt management of the recurrences holds the key to prolong OS and DFS. This review discusses the management options of HCC patients with PVTT.
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Affiliation(s)
- Abdul Rehman Khan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People's Republic of China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.,NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, People's Republic of China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, People's Republic of China
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Heller M, Parikh ND, Fidelman N, Owen D. Frontiers of therapy for hepatocellular carcinoma. Abdom Radiol (NY) 2021; 46:3648-3659. [PMID: 33837453 DOI: 10.1007/s00261-021-03065-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 12/30/2022]
Abstract
The incidence of hepatocellular carcinoma continues to increase worldwide. Fortunately, there have been notable recent advances in locoregional and systemic therapy. In this current review, we will highlight these new developments and future directions of hepatocellular carcinoma treatment and address the importance of a multidisciplinary approach to treatment.
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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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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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12
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Wu K, Shui Y, Sun W, Lin S, Pang H. Utility of Radiomics for Predicting Patient Survival in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Treated With Stereotactic Body Radiotherapy. Front Oncol 2020; 10:569435. [PMID: 33178598 PMCID: PMC7594107 DOI: 10.3389/fonc.2020.569435] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 09/16/2020] [Indexed: 01/27/2023] Open
Abstract
Introduction: This study aimed to develop and validate the combination of radiomic features and clinical characteristics that can predict patient survival in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) treated with stereotactic body radiotherapy (SBRT). Materials and Methods: The prediction model was developed in a primary cohort of 70 patients with HCC and PVTT treated with SBRT, using data acquired between December 2015 and June 2017. The radiomic features were extracted from computed tomography (CT) scans. A least absolute shrinkage and selection operator regression model was used to build the model. Multivariate Cox-regression hazard models were created for analyzing survival outcomes and the radiomic features and clinical characteristics were presented with a nomogram. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model. Participants were divided into a high-risk group and a low-risk group based on the radiomic features. Results: A total of four radiomic features and six clinical characteristics were extracted for survival analysis. A combination of the radiomic features and clinical characteristics resulted in better performance for the estimation of overall survival (OS) [area under the curve (AUC) = 0.859 (CI: 0.770–0.948)] than that with clinical characteristics alone [AUC = 0.761 (CI: 0.641–0.881)]. These patients were divided into high-risk and low-risk groups according to the radiomic features. Conclusion: This study demonstrated that a nomogram of combined radiomic features and clinical characteristics can be conveniently used to assess individualized preoperative prediction of OS in patients with HCC with PVTT before SBRT.
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Affiliation(s)
- Kui Wu
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yongjie Shui
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenzheng Sun
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Sheng Lin
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Haowen Pang
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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A case of advanced HCC treated with lenvatinib after hepatic arterial infusion chemotherapy combined with radiation therapy treatment for portal vein tumor thrombosis in the main trunk. Clin J Gastroenterol 2020; 13:839-843. [PMID: 31974811 DOI: 10.1007/s12328-020-01093-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 01/14/2020] [Indexed: 12/14/2022]
Abstract
We report a 46-year-old male patient with functional liver damage due to hepatitis B virus infection. A 12 cm hepatocellular carcinoma (HCC) in the left lobe and portal venous tumor thrombosis (PVTT) with vp4 (portal vein tumor thrombosis in the main trunk) were detected by computed tomography (CT). He underwent hepatic arterial infusion chemotherapy (HAIC) with cisplatin 100 mg for HCC and received radiation therapy (39 Gy/13 Fr) for PVTT with vp4. Follow-up CT showed reduction of HCC and reduced PVTT volume after 1 month of treatment. He then initiated lenvatinib therapy at 12 mg/day. One month later, follow-up CT showed no change in HCC size and a reduction in PVTT volume. Two months after initiating lenvatinib, follow-up CT showed no change in HCC, but further reduction in contrast effect and volume of PVTT. Three months after HAIC, he underwent drug-eluting-bead transcatheter arterial chemoembolization (DEB-TACE) with 100 mg of cisplatin (CDDP) for the HCC. After DEB-TACE, he received 12 mg/day with 5-days-on/2-days-off due to vomiting. One month after DEB-TACE, blood evaluation showed decreased tumor markers, and CT revealed that the HCC had grown slightly with no change in PVTT. Five months after HAIC, he underwent DEB-TACE with 100 mg of cisplatin for the HCC. A total of 150 days have passed since the start of lenvatinib treatment, and his Child-Pugh A status has been maintained.
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14
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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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15
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Wei X, Jiang Y, Zhang X, Feng S, Zhou B, Ye X, Xing H, Xu Y, Shi J, Guo W, Zhou D, Zhang H, Sun H, Huang C, Lu C, Zheng Y, Meng Y, Huang B, Cong W, Lau WY, Cheng S. Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study. J Clin Oncol 2019; 37:2141-2151. [PMID: 31283409 PMCID: PMC6698917 DOI: 10.1200/jco.18.02184] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients’ serum before RT and in surgical specimens was correlated with response to RT. RESULTS In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group (P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% (P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.
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Affiliation(s)
- Xubiao Wei
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Yabo Jiang
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Xiuping Zhang
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Shuang Feng
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Bin Zhou
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Xiaofei Ye
- 2Department of Health Statistics, Navy Military Medical University, Shanghai, People's Republic of China
| | - Hui Xing
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Ying Xu
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Jie Shi
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Weixing Guo
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Dong Zhou
- 3Fujian Provincial Cancer Hospital, Fuzhou, People's Republic of China
| | - Hui Zhang
- 3Fujian Provincial Cancer Hospital, Fuzhou, People's Republic of China
| | - Huichuan Sun
- 4Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Cheng Huang
- 4Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Congde Lu
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Yaxin Zheng
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Yan Meng
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Bin Huang
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Wenming Cong
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
| | - Wan Yee Lau
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China.,5The Chinese University of Hong Kong, Sha Tin, People's Republic of China
| | - Shuqun Cheng
- 1Eastern Hepatobiliary Surgery Hospital, Navy Military Medical University, Shanghai, People's Republic of China
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16
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Dose escalation by intensity modulated radiotherapy in liver-directed concurrent chemoradiotherapy for locally advanced BCLC stage C hepatocellular carcinoma. Radiother Oncol 2019; 133:1-8. [DOI: 10.1016/j.radonc.2018.12.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 12/19/2018] [Accepted: 12/20/2018] [Indexed: 12/22/2022]
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17
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Iwamoto H, Nomiyama M, Niizeki T, Shimose S, Shirono T, Nakano M, Satani M, Okamura S, Noda Y, Kamachi N, Sakai M, Suzuki H, Kuromatsu R, Ogo E, Abe T, Tanaka M, Koga H, Torimura T. Dose and Location of Irradiation Determine Survival for Patients with Hepatocellular Carcinoma with Macrovascular Invasion in External Beam Radiation Therapy. Oncology 2019; 96:192-199. [PMID: 30650415 DOI: 10.1159/000495568] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 11/19/2018] [Indexed: 12/28/2022]
Abstract
AIM Prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) is extremely poor. However, proper therapeutic strategies have not been established yet. The purpose of this study is to identify the effects of external beam radiation therapy (EBRT) for MVI of HCC. METHODS We have analyzed and evaluated 80 consecutive patients with HCC with MVI who underwent EBRT, and factors associated with enhanced survival in EBRT were evaluated by univariate and multivariate analysis. RESULTS The local response rate of radiotherapy for the irradiated MVI was 66.2%. The time to progression of the irradiated MVI was 5.8 months. Univariate and multivariate analyses showed that the higher irradiation dose (over 45 Gy) and the irradiation location (hepatic vein tumor thrombus - HVTT) were significant factors associated with survival benefits of EBRT. The response of EBRT for HVTT was significantly superior to that for portal vein or bile duct tumor thrombus. CONCLUSION We conclude that a multidisciplinary therapeutic strategy based on EBRT should be proactively selected in the treatment of advanced HCC with MVI.
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Affiliation(s)
- Hideki Iwamoto
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, .,Division of Liver Cancer Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan, .,Iwamoto Medical Clinic, Kitakyusyu, Japan,
| | - Mika Nomiyama
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takashi Niizeki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Shigeo Shimose
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Tomotake Shirono
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Masahito Nakano
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Manabu Satani
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Syusuke Okamura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yu Noda
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Naoki Kamachi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Miwa Sakai
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Hiroyuki Suzuki
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Etsuyo Ogo
- Department of Radiology, Kurume University School of Medicine, Kurume, Japan
| | - Toshi Abe
- Department of Radiology, Kurume University School of Medicine, Kurume, Japan
| | - Masatoshi Tanaka
- Department of Internal Medicine, Yokokura Hospital, Omuta, Japan
| | - Hironori Koga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.,Division of Liver Cancer Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.,Division of Liver Cancer Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan
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18
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Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review. Radiother Oncol 2018; 129:112-122. [DOI: 10.1016/j.radonc.2017.11.013] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 10/26/2017] [Accepted: 11/13/2017] [Indexed: 02/01/2023]
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19
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Saeki I, Yamasaki T, Maeda M, Hisanaga T, Iwamoto T, Fujisawa K, Matsumoto T, Hidaka I, Marumoto Y, Ishikawa T, Yamamoto N, Suehiro Y, Takami T, Sakaida I. Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy. World J Hepatol 2018; 10:571-584. [PMID: 30310535 PMCID: PMC6177565 DOI: 10.4254/wjh.v10.i9.571] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 07/30/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023] Open
Abstract
Sorafenib is used worldwide as a first-line standard systemic agent for advanced hepatocellular carcinoma (HCC) on the basis of the results of two large-scale Phase III trials. Conversely, hepatic arterial infusion chemotherapy (HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC, several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib, whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization, good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally, sorafenib is generally used to treat patients with Child-Pugh A, while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings, we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A, while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.
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Affiliation(s)
- Issei Saeki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Takahiro Yamasaki
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Masaki Maeda
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Takuro Hisanaga
- Department of Medical Education, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Takuya Iwamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Koichi Fujisawa
- Center of Research and Education for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi, 755-8505, Japan
| | - Toshihiko Matsumoto
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Isao Hidaka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Yoshio Marumoto
- Center for Clinical Research, Yamaguchi University Hospital, Yamaguchi 755-8505, Japan
| | - Tsuyoshi Ishikawa
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Naoki Yamamoto
- Yamaguchi University Health Administration Center, Yamaguchi 753-8511, Japan
| | - Yutaka Suehiro
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 755-8505, Japan
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Su F, Chen K, Liang Z, Wu C, Li L, Qu S, Chen L, Zhu X, Zhong J, Li L, Xiang B. Comparison of three-dimensional conformal radiotherapy and hepatic resection in hepatocellular carcinoma with portal vein tumor thrombus. Cancer Med 2018; 7:4387-4395. [PMID: 30062844 PMCID: PMC6144153 DOI: 10.1002/cam4.1708] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 07/07/2018] [Accepted: 07/09/2018] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVE This study aimed to evaluate the safety and efficacy of three-dimensional conformal radiotherapy (3D-CRT) and hepatic resection for patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT). METHODS We retrospectively analyzed 323 HCC patients involving PVTT. Among them, 134 patients underwent 3D-CRT, while 189 controls treated with hepatic resection (HR). Survival rate and prognostic analysis were performed using Kaplan-Meier method and Cox regression analyses. RESULTS The 1-, 2-, and 3-year overall survival (OS) of RT group and HR group was 54% vs 62%, 33% vs 47%, and 18% vs 43%, respectively (P = 0.003). In the subgroup of PVTT type analysis, the 1-, 2-, and 3-year OS in RT group was 65%, 39%, and 19%, respectively, while that in HR group was 83%, 53%, and 42%, respectively, in type I PVTT (P < 0.001). The 1-, 2-, and 3-year OS in RT group was 52%, 35%, and 11%, while that in HR group was 55%, 42%, and 25%, respectively, in type II PVTT (P = 0.612). In type III PVTT, the 1-, 2-, and 3-year OS in RT group was 16%, 3%, and 0%, respectively, while that in HR group was 11%, 0%, and 0%, respectively (P = 0.041). Multivariate analysis revealed that tumor size ≥10 cm, Child-Pugh class B, and type III PVTT are independent predictors of poor prognosis in HCC with PVTT. CONCLUSION 3D-CRT appears to be an effective treatment for patients with HCC involving type II/III PVTT.
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Affiliation(s)
- Fang Su
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Kai‐Hua Chen
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Zhong‐Guo Liang
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Chun‐Hua Wu
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Ling Li
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Song Qu
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Long Chen
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Xiao‐Dong Zhu
- Department of Radiation OncologyAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Jian‐Hong Zhong
- Hepatobiliary Surgery DepartmentAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Le‐Qun Li
- Hepatobiliary Surgery DepartmentAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
| | - Bang‐De Xiang
- Hepatobiliary Surgery DepartmentAffiliated Tumor Hospital of Guangxi Medical UniversityCancer Institute of Guangxi Zhuang Autonomous RegionNanningChina
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Li MF, Leung HW, Chan AL, Wang SY. Network meta-analysis of treatment regimens for inoperable advanced hepatocellular carcinoma with portal vein invasion. Ther Clin Risk Manag 2018; 14:1157-1168. [PMID: 30013351 PMCID: PMC6038877 DOI: 10.2147/tcrm.s162898] [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] [Indexed: 12/12/2022] Open
Abstract
Purpose We assessed the efficacy and safety of different modalities using the network meta-analysis for inoperable hepatocellular carcinoma (HCC) with portal vein invasion. The interested modalities included stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE), three-dimensional radiotherapy (3D-RT) combined with hepatic arterial infusion chemotherapy (HAIC) or TACE, TACE plus sorafenib, and use of SBRT, HAIC, sorafenib, and TACE alone. Methods PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to June 2017. We used network meta-analysis to compare the disease control rate (DCR) and severe adverse events for the eight interested regimens included in this analysis. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. Results Fifteen studies published between 2010 and 2016 involving a total of 2,359 patients were enrolled in this network meta-analysis. With indirect comparison of DCR and overall safety, the pooled results showed that RT plus HAIC was the most effective regimen in treating advanced HCC with portal vein tumor thrombosis, followed by RT plus TACE. HAIC alone and sorafenib combined with HAIC appeared least effective intervention regimens. The incidence of treatment-related adverse events of grade 3 or 4 occurred less in the patients who received SBRT alone compared with other interested regimens. Conclusion 3D-RT combined with HAIC or TACE showed more favorable treatment responses compared with other regimens in advanced HCC patients with portal vein tumor thrombosis.
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Affiliation(s)
- Ming-Feng Li
- Department of Medical Imaging, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan.,Department of Radiology, An-Nan Hospital, China Medical University, Tainan, Taiwan,
| | - Henry Wc Leung
- Department of Radiation Oncology, An-Nan Hospital, China Medical University, Tainan, Taiwan,
| | - Agnes Lf Chan
- Department of Pharmacy, An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Shyh-Yau Wang
- Department of Radiology, An-Nan Hospital, China Medical University, Tainan, Taiwan,
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22
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Lee SW, Lee HL, Han NI, Kwon JH, Nam SW, Jang JW, Bae SH, Choi JY, Yoon SK. Transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil versus transarterial chemoembolization using doxorubicin for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective analysis. Ther Adv Med Oncol 2017; 9:615-626. [PMID: 28974984 PMCID: PMC5613859 DOI: 10.1177/1758834017728018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 07/03/2017] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND More than one-third of hepatocellular carcinoma (HCC) patients are diagnosed at advanced stage with portal vein tumor thrombosis (PVTT) or extrahepatic metastasis. However, the outcomes of current therapeutic approaches are unsatisfactory. As a novel therapeutic strategy for unresectable HCC with PVTT, we analyzed the outcomes of transarterial infusion of epirubicin and cisplatin combined with systemic infusion of 5-fluorouracil (TAC-ECF) and compared its therapeutic effects and toxicity with transarterial chemoembolization (TACE) using doxorubicin (DOX). METHODS A total of 540 consecutive HCC patients who received TACE at the Catholic Medical Center between January 2007 and November 2013 were enrolled. Of these patients, we retrospectively analyzed 129 Barcelona clinic liver cancer stage C HCC patients with PVTT who received either TAC-ECF or TACE using DOX. RESULTS The objective tumor response rate was higher in the TAC-ECF group, with 31.3% objective response rate after TAC-ECF compared to 10% after DOX treatment (p = 0.004). Median follow-up period was 7 months (range, 1-57 months). The overall survival rate was also significantly higher in the TAC-ECF group compared to the DOX group (median 9.3 versus 4.6 months, p < 0.0001). Multivariate analysis revealed that TAC-ECF and extrahepatic metastasis were independent predictive factors for overall survival (p < 0.0001 and p = 0.002 respectively). No serious adverse effects developed in both groups. CONCLUSIONS TAC-ECF therapy was tolerable and showed higher overall survival rate and tumor response compared to the conventional TACE DOX in advanced stage HCC patients with PVTT. Therefore, TAC-ECF may be considered as an effective treatment option for patients with unresectable HCC.
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Affiliation(s)
- Sung Won Lee
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hae Lim Lee
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Nam Ik Han
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Hyun Kwon
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Soon Woo Nam
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Won Jang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Si Hyun Bae
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Young Choi
- Division of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary’s hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Republic of Korea
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Zhang J, Wu N, Lian Z, Feng H, Jiang Q, Chen X, Gong J, Qiao Z. The Combined Antitumor Effects of 125I Radioactive Particle Implantation and Cytokine-Induced Killer Cell Therapy on Xenograft Hepatocellular Carcinoma in a Mouse Model. Technol Cancer Res Treat 2017; 16:1083-1091. [PMID: 29332456 PMCID: PMC5762075 DOI: 10.1177/1533034617732204] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The combination of radiotherapy and immunotherapy has shown great promise in eradicating tumors. For example, 125I radioactive particle implantation and cytokine-induced killer cell therapies have demonstrated efficacy in treating hepatocellular carcinoma. However, the mechanism of this combination therapy remains unknown. In this study, we utilized cytokine-induced killer cells obtained from human peripheral blood mononuclear cells along with 125I radioactive particle implantation to treat subcutaneous hepatocellular carcinoma xenograft tumors in BALB/c nude mice. The effects of combination therapy on tumor growth, tumor cell apoptosis and proliferation, animal survival, and immune indexes were then assessed. The results indicated that 125I radioactive particle implantation combined with cytokine-induced killer cells shows a much greater antitumor therapeutic effect than either of the therapies alone when compared to control treatments. Mice treated with a combination of radiotherapy and immunotherapy displayed significantly reduced tumor growth. 125I radioactive particle implantation upregulated the expression of major histocompatibility complex (MHC) class I chain-related gene A in hepatocellular carcinoma cells and enhanced cytokine-induced killer cell–mediated apoptosis through activation of caspase-3. Furthermore, cytokine-induced killer cells supplied immune substrates to induce a strong immune response after 125I radioactive particle implantation therapy. In conclusion, 125I radioactive particle implantation combined with cytokine-induced killer cell therapy significantly inhibits the growth of human hepatocellular carcinoma cells in vivo and improves animal survival times through mutual promotion of antitumor immunity, presenting a promising therapy for hepatocellular carcinoma.
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Affiliation(s)
- Junyong Zhang
- 1 Chongqing Key Laboratory of Hepatobiliary Surgery, Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.,2 Department of Urology Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Nian Wu
- 3 Department of General Surgery, the Fifth People's Hospital of Chongqing City, Chongqing, People's Republic of China
| | - Zhengrong Lian
- 4 Department of Clinical Epidemiology and Biostatistics, Population Health Research Institution, McMaster University, Hamilton, Ontario, Canada
| | - Huyi Feng
- 3 Department of General Surgery, the Fifth People's Hospital of Chongqing City, Chongqing, People's Republic of China
| | - Qing Jiang
- 2 Department of Urology Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Xianfeng Chen
- 5 Department of Hepatobiliary Surgery, Fuling Center Hospital, Fuling District, Chongqing, People's Republic of China
| | - Jianping Gong
- 1 Chongqing Key Laboratory of Hepatobiliary Surgery, Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China
| | - Zhengrong Qiao
- 6 Department of General Surgery, People's Hospital of Changshou District, Chongqing, People's Republic of China
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Hepatectomy after down-staging of hepatocellular carcinoma with portal vein tumor thrombus using chemoradiotherapy: A retrospective cohort study. Int J Surg 2017; 44:223-228. [DOI: 10.1016/j.ijsu.2017.06.082] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Accepted: 06/27/2017] [Indexed: 12/15/2022]
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Moriguchi M, Furuta M, Itoh Y. A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus. J Clin Transl Hepatol 2017; 5:177-183. [PMID: 28660156 PMCID: PMC5472939 DOI: 10.14218/jcth.2016.00075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 02/21/2017] [Accepted: 02/25/2017] [Indexed: 12/12/2022] Open
Abstract
Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC. In many cases of HCC with advanced PVTT, treatment is difficult because the tumor has considerable extension into the liver, and portal hypertension is a frequent complication. The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function. However, the outcomes of sorafenib therapy are not completely satisfactory, making the development of another therapy an urgent task. Therefore, this review aims to summarize non-operative treatments for HCC with advanced PVTT and discuss future perspectives based on those therapies, including therapies still being developed.
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Affiliation(s)
- Michihisa Moriguchi
- *Correspondence to: Michihisa Moriguchi, Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokouji, Kamigyo-ku, Kyoto 602-8566, Japan. Tel: +81-75-251-5519, Fax: +81-75-0251-0710, E-mail:
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Ye JZ, Wang YY, Bai T, Chen J, Xiang BD, Wu FX, Li LQ. Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update. Oncotarget 2017; 8:93258-93278. [PMID: 29190996 PMCID: PMC5696262 DOI: 10.18632/oncotarget.18735] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 04/25/2017] [Indexed: 01/27/2023] Open
Abstract
Portal vein tumor thrombus (PVTT) usually worsens prognosis of hepatocellular carcinoma (HCC), as characterized by aggressive disease progression, impaired liver function and tolerance to treatment. Conventionally, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) accepted the Barcelona Clinical Liver Cancer (BCLC) treatment algorithms, identifying PVTT as an absolute contra-indication of surgical resection for HCC. HCC-PVTT patients are offered sorafenib as the standard treatment. Evidently, SHARP and Asia-Pacific trials demonstrated that sorafenib only improves overall survival by approximately 3 months in patients with advanced HCC. Besides, BCLC treatment algorithm does not provide different therapeutic recommendations for different degree of PVTT, and only supports single treatment option for each stage of HCC rather than a combination of comprehensive treatments, which limited individual and best care for every HCC-PVTT patients. In the past few years, many surgeons do not restrict surgical resection to HCC with PVTT. There have been new reports demonstrated that surgical treatment is feasible for selected HCC-PVTT patients with resectable tumor and moderate liver function to prolong survival period and elevate life quality as long as PVTT limited to the first-order branch, whereas non-surgical treatments fail to provide comparable therapeutic effects. At present, guidelines on HCC management from mainland China, Japan, and Hong Kong have been updated and a consensus of Asia-Pacific experts has established that portal venous invasion is not an absolute contradiction of surgical resection for HCC. This review summarized the emerging data on surgical resection for HCC-PVTT patients beyond the BCLC treatment algorithms and discussed recent therapeutic conceptualchanges in the Asia-Pacific region.
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Affiliation(s)
- Jia-Zhou Ye
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Yan-Yan Wang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Jie Chen
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Bang-De Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
| | - Le-Qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, PR China
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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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Chen MY, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Tsang NM, Chan KM, Lee WC. Efficacy of External Beam Radiation-Based Treatment plus Locoregional Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:6017406. [PMID: 27999803 PMCID: PMC5143704 DOI: 10.1155/2016/6017406] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 11/03/2016] [Accepted: 11/07/2016] [Indexed: 01/22/2023]
Abstract
Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management.
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Affiliation(s)
- Ming-Yang Chen
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Yu XJ, Zhao Q, Wang XB, Zhang JX, Wang XB. Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents. Oncol Rep 2016; 36:3611-3618. [PMID: 27779687 DOI: 10.3892/or.2016.5188] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Accepted: 05/11/2016] [Indexed: 11/06/2022] Open
Abstract
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is overexpressed in many human malignancies. It regulates phosphorylated AKT and stabilizes c‑Myc in cell proliferation and tumor formation, suggesting that CIP2A plays an essential role in the development of cancer. In the present study, we report that a natural compound, gambogenic acid (GEA), induced the degradation of CIP2A via the ubiquitin‑proteasome pathway. Interestingly, the combination of GEA and proteasome inhibitors potentiated the accumulation of ubiquitinated CIP2A and aggresome formation. In addition, GEA exhibited an inhibitory effect on cell proliferation and CIP2A‑downstream signaling molecules (c‑Myc and pAKT). Furthermore, GEA and CIP2A silencing enhanced the chemosensitivity of hepatocellular carcinoma cells to anticancer agents, suggesting that a combination of a CIP2A inhibitor and anticancer agents could be a valuable clinical therapeutic strategy. These results indicate that GEA is a CIP2A inhibitor that interferes with the ubiquitination and destabilization of CIP2A, providing a promising strategy to enhance the combinational therapy for hepatocellular carcinoma.
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Affiliation(s)
- Xian-Jun Yu
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital and School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Qun Zhao
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
| | - Xuan-Bin Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital and School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Jing-Xuan Zhang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital and School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Xiao-Bo Wang
- Center for Translational Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei 441300, P.R. China
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Li N, Feng S, Xue J, Wei XB, Shi J, Guo WX, Lau WY, Wu MC, Cheng SQ, Meng Y. Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy. HPB (Oxford) 2016; 18:549-56. [PMID: 27317960 PMCID: PMC4913143 DOI: 10.1016/j.hpb.2016.04.003] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Revised: 03/20/2016] [Accepted: 04/10/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) has a poor prognosis even after surgical resection. Whether neoadjuvant radiotherapy improves surgical outcomes is currently unknown. The aim of this study was to compare the survival of patients with resectable HCC and mPVTT who underwent neoadjuvant therapy to those who underwent surgery alone. METHODS A non-randomized comparative study was performed. For patients in the neoadjuvant radiotherapy group, three-dimensional conformal radiotherapy was administrated with a daily fraction of 300 cGy in 6 consecutive days. Hepatectomy was carried out 4 weeks after completion of irradiation. RESULTS 95 patients were enrolled into this study. In the neoadjuvant radiotherapy group (n = 45), 12 patients showed gross radiological reduction in extent of PVTT. In 6 patients, the extent of PVTT was reduced to be within the ipsilateral side of the portal vein. When compared with patients who underwent surgery alone (n = 50), neoadjuvant radiotherapy significantly decreased the rates of HCC recurrence and HCC-related death, with hazard ratios of 0.36 (95% CI, 0.19-0.70) and 0.32 (95% CI, 0.18-0.57), respectively. CONCLUSION For patients with HCC with mPVTT, neoadjuvant radiotherapy before partial hepatectomy provided better postoperative survival outcomes than partial hepatectomy alone.
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Affiliation(s)
- Nan Li
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shuang Feng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Xue
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xu-Biao Wei
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Yee Lau
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Meng-Chao Wu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Correspondence Shu-Qun Cheng, Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.Department of Hepatic Surgery VIEastern Hepatobiliary Surgery HospitalSecond Military Medical University225 Changhai RoadShanghai200433China
| | - Yan Meng
- Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China,Correspondence Yan Meng, Department of Radiotherapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.Department of RadiotherapyEastern Hepatobiliary Surgery HospitalSecond Military Medical University225 Changhai RoadShanghai200433China
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Han K, Kim JH, Ko GY, Gwon DI, Sung KB. Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review. World J Gastroenterol 2016; 22:407-416. [PMID: 26755886 PMCID: PMC4698503 DOI: 10.3748/wjg.v22.i1.407] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 10/15/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
The natural history of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal (approximately 2-4 mo), and PVTT is reportedly found in 10%-40% of HCC patients at diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) Staging System (which is the most widely adopted HCC management guideline), sorafenib is the standard of care for advanced HCC (i.e., BCLC stage C) and the presence of PVTT is included in this category. However, sorafenib treatment only marginally prolongs patient survival and, notably, its therapeutic efficacy is reduced in patients with PVTT. In this context, there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options. To date, many studies on transarterial chemoembolization, 3-dimensional conformal radiotherapy, hepatic arterial chemotherapy, and transarterial radioembolization report better overall survival than sorafenib therapy alone, but their outcomes need to be verified in future prospective, randomized controlled studies in order to be incorporated into current treatment guidelines. Additionally, combination strategies have been applied to treat HCC patients with PVTT, with the hope that the possible synergistic actions among different treatment modalities would provide promising results. This narrative review describes the current status of the management options for HCC with PVTT, with a focus on overall survival.
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Yim HJ, Suh SJ, Um SH. Current management of hepatocellular carcinoma: an Eastern perspective. World J Gastroenterol 2015; 21:3826-42. [PMID: 25852267 PMCID: PMC4385529 DOI: 10.3748/wjg.v21.i13.3826] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 12/11/2014] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.
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Qi WX, Fu S, Zhang Q, Guo XM. Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis. Radiother Oncol 2014; 114:289-95. [PMID: 25497556 DOI: 10.1016/j.radonc.2014.11.033] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2014] [Revised: 11/03/2014] [Accepted: 11/20/2014] [Indexed: 12/13/2022]
Abstract
PURPOSE To perform a systematic review and meta-analysis to compare the clinical outcomes and toxicity of hepatocellular carcinoma (HCC) patients treated with charged particle therapy (CPT) with those of individuals receiving photon therapy. METHODS We identified relevant clinical studies through searching databases. Primary outcomes of interest were overall survival (OS) at 1, 3, 5 years, progression-free survival (PFS), and locoregional control (LC) at longest follow-up. RESULTS 73 cohorts from 70 non-comparative observational studies were included. Pooled OS was significantly higher at 1, 3, 5 years for CPT than for conventional radiotherapy (CRT) [relative risk (RR) 1·68, 95% CI 1·22-2·31; p<0·001; RR 3.46, 95% CI: 1.72-3.51, p<0.001; RR 25.9, 95% CI: 1.64-408.5, p=0.02; respectively]. PFS and LC at longest follow-up was also significantly higher for CPT than for CRT (p=0·013 and p<0.001, respectively), while comparable efficacy was found between CPT and SBRT in terms of OS, PFS and LC at longest follow-up. Additionally, high-grade acute and late toxicity associated with CPT was lower than that of CRT and SBRT. CONCLUSION Survival rates for CPT are higher than those for CRT, but similar to SBRT in patients with HCC. Toxicity tends to be lower for CPT compared to photon radiotherapy.
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Affiliation(s)
- Wei-Xiang Qi
- Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, China
| | - Shen Fu
- Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, China.
| | - Qing Zhang
- Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, China
| | - Xiao-Mao Guo
- Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, China
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Onishi H, Nouso K, Nakamura S, Katsui K, Wada N, Morimoto Y, Miyahara K, Takeuchi Y, Kuwaki K, Yasunaka T, Miyake Y, Shiraha H, Takaki A, Kobayashi Y, Sakaguchi K, Kanazawa S, Yamamoto K. Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion. Hepatol Int 2014; 9:105-12. [PMID: 25788384 DOI: 10.1007/s12072-014-9592-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 10/23/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients. METHODS We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT). RESULTS Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18%, p < 0.01) and PVTT (45 vs. 18%, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively). CONCLUSIONS CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.
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Affiliation(s)
- Hideki Onishi
- Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City, Okayama, 700-8558, Japan,
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