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Chami P, Diab Y, Khalil DN, Azhari H, Jarnagin WR, Abou-Alfa GK, Harding JJ, Hajj J, Ma J, El Homsi M, Reyngold M, Crane C, Hajj C. Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:16773. [PMID: 38069095 PMCID: PMC10706661 DOI: 10.3390/ijms242316773] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/24/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open
Abstract
The liver tumor immune microenvironment has been thought to possess a critical role in the development and progression of hepatocellular carcinoma (HCC). Despite the approval of immune checkpoint inhibitors (ICIs), such as programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, for several types of cancers, including HCC, liver metastases have shown evidence of resistance or poor response to immunotherapies. Radiation therapy (RT) has displayed evidence of immunosuppressive effects through the upregulation of immune checkpoint molecules post-treatment. However, it was revealed that the limitations of ICIs can be overcome through the use of RT, as it can reshape the liver immune microenvironment. Moreover, ICIs are able to overcome the RT-induced inhibitory signals, effectively restoring anti-tumor activity. Owing to the synergetic effect believed to arise from the combination of ICIs with RT, several clinical trials are currently ongoing to assess the efficacy and safety of this treatment for patients with HCC.
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Affiliation(s)
- Perla Chami
- Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon;
| | - Youssef Diab
- Faculty of Medicine, University of Balamand, Beirut 1100, Lebanon; (Y.D.)
| | - Danny N. Khalil
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Hassan Azhari
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - William R. Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Surgery, Weill Medical College, Cornell University, New York, NY 10021, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA
| | - James J. Harding
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA
| | - Joseph Hajj
- Faculty of Medicine, University of Balamand, Beirut 1100, Lebanon; (Y.D.)
| | - Jennifer Ma
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Maria El Homsi
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Marsha Reyngold
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | | | - Carla Hajj
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- New York Proton Center, New York, NY 10035, USA
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Chami P, Jarnagin W, Abou-Alfa GK, Harding J, Kim N, Lin H, El Homsi M, Crane C, Hajj C. Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:1748. [PMID: 36980634 PMCID: PMC10046599 DOI: 10.3390/cancers15061748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.
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Affiliation(s)
- Perla Chami
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon
| | - William Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Surgery, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - James Harding
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Neal Kim
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Haibo Lin
- New York Proton Center, New York, NY 10035, USA
| | - Maria El Homsi
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | | | - Carla Hajj
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- New York Proton Center, New York, NY 10035, USA
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Tong VJW, Shelat VG, Chao YK. Clinical application of advances and innovation in radiation treatment of hepatocellular carcinoma. J Clin Transl Res 2021; 7:811-833. [PMID: 34988334 PMCID: PMC8715712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 09/22/2021] [Accepted: 09/29/2021] [Indexed: 02/08/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) management has evolved over the past two decades, with the development of newer treatment modalities. While various options are available, unmet needs are reflected through the mixed treatment outcome for intermediate-stage HCC. As HCC is radiosensitive, radiation therapies have a significant role in management. Radiation therapies offer local control for unresectable lesions and for patients who are not surgical candidates. Radiotherapy also provides palliation in metastatic disease, and acts as a bridge to resection and transplantation in selected patients. Advancements in radiotherapy modalities offer improved dose planning and targeted delivery, allowing for better tumor response and safer dose escalations while minimizing the risks of radiation-induced liver damage. Radiotherapy modalities are broadly classified into external beam radiation therapy and selective internal radiation therapy. With emerging modalities, radiotherapy plays a complementary role in the multidisciplinary care of HCC patients. Aim We aim to provide an overview of the role and clinical application of radiation therapies in HCC management. Relevance for Patients The continuous evolution of radiotherapy techniques allows for improved therapeutic outcomes while mitigating unwanted adverse effects, making it an attractive modality in HCC management. Rigorous clinical studies, quality research and comprehensive datasets will further its application in the present era of evidence-based practice in Medicine.
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Affiliation(s)
- Valerie J. W. Tong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Vishal G. Shelat
- Department of General Surgery, Tan Tock Seng Hospital, 308433, Singapore
| | - Yew Kuo Chao
- Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, 308433, Singapore
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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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Lee SJ, Jang HS, Choi YK. Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study. Medicine (Baltimore) 2021; 100:e26390. [PMID: 34160420 PMCID: PMC8238290 DOI: 10.1097/md.0000000000026390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45-55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3-26.5 months). The median overall survival was 9.4 months (range, 3.7-26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.
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Xia Y, Zhang J, Ni X. Diagnosis, treatment and prognosis of hepatocellular carcinoma with inferior vena cava/right atrium tumor thrombus. Oncol Lett 2020; 20:101. [PMID: 32831920 PMCID: PMC7439153 DOI: 10.3892/ol.2020.11962] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Accepted: 06/26/2020] [Indexed: 02/06/2023] Open
Abstract
Although tumor thrombus (TT) infringement of the inferior vena cava (IVC) and right atrium (RA) is rarely observed in hepatocellular carcinoma (HCC), the prognosis for this condition is extremely poor, with a median survival time of several months, given that the condition is often diagnosed at an advanced tumor stage or combined with multiple systemic metastases. Furthermore, there is no established effective treatment for the condition. However, some investigators insist that active treatment, including surgery, chemotherapy (systemic or intra-arterial), radiation therapy, best supportive care or a combination of these, may help prolong overall survival time in these patients. The management of patients with advanced HCC and a TT extending into the RA and IVC is extremely difficult and risky. To this end, the present review assessed the literature on the clinical features and treatments of this condition in recent years, with the aim of providing assistance for clinical work.
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Affiliation(s)
- Yinchuan Xia
- Department of Oncology, Bazhong Central Hospital, Bazhong, Sichuan 636000, P.R. China
| | - Junqi Zhang
- Department of Oncology, Bazhong Central Hospital, Bazhong, Sichuan 636000, P.R. China
| | - Xiaoling Ni
- Department of Oncology, Bazhong Central Hospital, Bazhong, Sichuan 636000, P.R. China
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Sekino Y, Okumura T, Fukumitsu N, Iizumi T, Numajiri H, Mizumoto M, Nakai K, Nonaka T, Ishikawa H, Sakurai H. Proton beam therapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus. J Cancer Res Clin Oncol 2020; 146:711-720. [PMID: 31776663 DOI: 10.1007/s00432-019-03096-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 11/21/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT) is rare and regarded as an advanced disease stage with poor prognosis. Treatment effect data regarding HCC with IVCTT is scarce and clear evidence has not been established. This study, therefore, aims to examine the safety and effectiveness of proton beam therapy (PBT) for HCC patients with IVCTT. METHODS From January 2005 to December 2014, a total of 21 HCC patients with IVCTT were analyzed. The total irradiation doses ranged from 50 to 74 (median 72.6) gray relative biological effectiveness. RESULTS The follow-up period was 4-120 (median 21) months. Regarding acute toxicities, dermatitis of grade 1-2 was observed in all patients, while no grade 3 or higher late toxicity events were encountered. The overall survival (OS) rates for all patients were 62%, 33%, and 19% at 1, 2, and 3 years, respectively. No local recurrences for the treated lesions, including IVCTT, were observed. According to univariate analysis, IVCTT extension type was not associated with prognosis, but only tumor number significantly affected the OS rate (p = 0.003). For 10 single lesion patients, the longest survival time was 120 months with OS rates of 82%, 64%, and 36% at 1, 2, and 3 years, respectively. CONCLUSION PBT is safe and effective for HCC patients with IVCTT, especially those with single lesion status. PBT is an important treatment option for HCC patients with IVCTT.
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Affiliation(s)
- Yuta Sekino
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan.
| | - Toshiyuki Okumura
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Nobuyoshi Fukumitsu
- Kobe Proton Center, 1-6-8 Minatojima Minamimachi, Chuo-ku, Kobe, 650-0047, Japan
| | - Takashi Iizumi
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Haruko Numajiri
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Masashi Mizumoto
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Kei Nakai
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Tetsuo Nonaka
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Hitoshi Ishikawa
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Japan
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Rim CH, Jeong BK, Kim TH, Hee Kim J, Kang HC, Seong J. Effectiveness and feasibility of external beam radiotherapy for hepatocellular carcinoma with inferior vena cava and/or right atrium involvement: a multicenter trial in Korea (KROG 17-10). Int J Radiat Biol 2020; 96:759-766. [PMID: 31977276 DOI: 10.1080/09553002.2020.1721607] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be established due to its rarity and intractability. We sought to determine the clinical efficacy of external beam radiotherapy (EBRT) in HCC treatment.Patients and methods: Our group designed this multicenter trial and recruited patients with HCC and IVC and/or RA involvement. Forty-nine patients from six institutions received EBRT with median dose of 46.7 (range: 35.4-71.5) Gy during 2009-2016. The primary outcome was overall survival (OS), and relevant predictors were evaluated.Results: Median follow-up length was 9.3 (range: 1.1-119) months. Median survival, 1-, and 2- year OS rates were 10.1 months (95% confidence interval [CI]: 7.5-12.7 months), 43.5%, and 30.1%, respectively. Significant factors affecting OS were alpha-fetoprotein level ≥300 ng/mL (risk ratio [RR]: 2.34, p = .025), tumor multiplicity (RR: 2.56, p = .028), and patient volume of institutions (high- vs. middle volume centers) (RR: 3.58, p = .001). Local control rates were 88.7% and 74.5% at 1 and 2 years, respectively. The most common first failure site was the lung (21/49, 42.9%) followed by liver outside the EBRT field (17/49, 34.7%). One case of possible radiation-induced liver disease was noted, with transient alkaline phosphatase elevation.Conclusion: EBRT can yield favorable local control in HCC with IVC and/or RA involvement. Systemic treatment may be more indicated as factors reflecting tumor aggressiveness were significant, and first distant failure is common.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Korea University Medical College, Seoul, Korea
| | - Bae-Kwon Jeong
- Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Gyeonggido, Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Korea
| | - Hyun-Cheol Kang
- Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
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Mourad M, Mabrut JY, Chellakhi M, Lesurtel M, Prevost C, Ducerf C, Rode A, Merle P, Mornex F, Mohkam K. Neoadjuvant conformal radiotherapy before liver transplantation for hepatocellular carcinoma: a propensity score matched analysis of postoperative morbidity and oncological results. Future Oncol 2019; 15:2517-2530. [DOI: 10.2217/fon-2019-0127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Aim: To assess neoadjuvant conformal radiotherapy (CRT) before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) not suitable for standard locoregional treatments. Methods: Patients undergoing OLT for HCC with or without prior CRT were compared using 1:3 propensity score matching. Results: After propensity score matching, 23 patients with CRT were compared with 66 control subjects. Severe morbidity rate was 34.8 versus 24.2% in the CRT and non-CRT groups (p = 0.289). Complete pathological response was observed in 47.8% of CRT-targeted nodules. The 1-/3-/5-year disease-free survivals were 77.3, 77.3 and 68.7% in the CRT group versus 85.4, 68.0 and 61.7% in the non-CRT group (p = 0.829). Conclusion: Conformal radiotherapy represents a satisfactory neoadjuvant therapy for OLT candidates not suitable for standard HCC locoregional therapies.
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Affiliation(s)
- Mohamed Mourad
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
- Ecole Doctorale Biologie Moléculaire Intégrative et Cellulaire (BMIC), Claude Bernard Lyon 1 University, Lyon, France
- Department of General & Digestive Surgery, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Jean-Yves Mabrut
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Madiha Chellakhi
- Department of Oncology & Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Mickaël Lesurtel
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Célia Prevost
- Department of Oncology & Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Christian Ducerf
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
| | - Agnès Rode
- Department of Radiology, Hospices Civils de Lyon, Croix-Rousse University Hospital, Lyon, France
| | - Philippe Merle
- Department of Hepatology, Hospices Civils de Lyon, Croix-Rousse University Hospital, Lyon, France
| | - Françoise Mornex
- Department of Oncology & Radiotherapy, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Kayvan Mohkam
- Department of General Surgery & Liver Transplantation, Hospices Civils de Lyon, Croix-Rousse University Hospital, Claude-Bernard Lyon 1 University, Lyon, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) Unit U1052, Cancer Research Center of Lyon, Lyon, France
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Pao TH, Hsueh WT, Chang WL, Chiang NJ, Lin YJ, Liu YS, Lin FC. Radiotherapy for inferior vena cava tumor thrombus in patients with hepatocellular carcinoma. BMC Cancer 2019; 19:560. [PMID: 31182065 PMCID: PMC6558860 DOI: 10.1186/s12885-019-5654-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 04/29/2019] [Indexed: 01/14/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) with inferior vena cava (IVC) involvement is a rare disease with poor prognosis. This study aimed to evaluate the outcome of HCC patients receiving radiotherapy (RT) to IVC tumor thrombus. Methods A total of 42 consecutive HCC patients treated with RT to IVC tumor thrombus between September 2007 and October 2018 were enrolled. Overall survival (OS), the response of IVC thrombus, prognostic factors and failure pattern were assessed. Results The median follow-up time was 4.4 months. The median RT equivalent dose in 2-Gy fractions was 48.75 Gy (range, 3.25–67.10). The objective response rate of IVC thrombus was 47.6% (95% confidence interval [CI], 33.3–64.3%). The OS rate at 1 year was 30.0%, with a median OS of 6.6 months (95% CI, 3.7–9.5) from the start of RT. On multivariate analysis, Child-Pugh class, lymph node metastasis, lung metastasis and objective response of IVC thrombus were independent predictors for OS. Lung was the most common site of first progression in 14 (33.3%) patients. For 32 patients without lung metastasis before RT, use of systemic treatment concurrent with and/or after RT was associated with a significantly longer lung metastasis-free survival (5.9 vs. 1.5 months, p = 0.0033). Conclusions RT is effective for IVC tumor thrombus of HCC with acceptable adverse effects. RT might be a treatment option incorporated into combination therapy for HCC involving IVC.
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Affiliation(s)
- Tzu-Hui Pao
- Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 70456, Taiwan
| | - Wei-Ting Hsueh
- Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 70456, Taiwan
| | - Wei-Lun Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Nai-Jung Chiang
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.,National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.,Division of Hematology/Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Yih-Jyh Lin
- Division of Transplant surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Sheng Liu
- Department of Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Forn-Chia Lin
- Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 70456, Taiwan.
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Rim CH, Kim CY, Yang DS, Yoon WS. External beam radiation therapy to hepatocellular carcinoma involving inferior vena cava and/or right atrium: A meta-analysis and systemic review. Radiother Oncol 2018; 129:123-129. [PMID: 29606524 DOI: 10.1016/j.radonc.2018.02.030] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 02/25/2018] [Accepted: 02/26/2018] [Indexed: 12/24/2022]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) involving inferior vena cava (IVC) and/or right atrium (RA) is a very rare but serious disease. The objective of this meta-analysis was to assess efficacy and safety of external beam radiotherapy (EBRT) for HCC involving IVC and/or RA. MATERIALS AND METHODS Systematic search of Pubmed, MEDLINE, EMBASE, and Cochrane library published was performed. Primary endpoints were 1-year overall survival (OS) rate and 2-year OS rates. Secondary endpoints were response rate, local control (LC) rate, and grade ≥3 toxicities. According to heterogeneity evaluated with Cochran Q test and I2 statistics, meta-analysis was performed using either random or fixed model. RESULTS A total of 8 studies and 9 cohorts were included, encompassing 164 patients. Pooled 1- and 2-year OS rates were 53.6% (95% CI: 45.7-61.3%) and 36.9% (95% CI: 27.2-42.4%), respectively. Pooled response rate and LC rate were 59.2% (95% CI: 39.0-76.7%) and 83.8% (95% CI: 78.8-97.1%), respectively. Only one study reported 2 grade ≥3 toxicities, an esophageal rupture and a pulmonary embolism cases. The overall rate of possible grade ≥3 complications was 1.2% (2 of 164). CONCLUSIONS EBRT is a feasible and safe option to palliate HCC with IVC and/or RA invasion.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Republic of Korea
| | - Chul Yong Kim
- Department of Radiation Oncology, Anam Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Dae Sik Yang
- Department of Radiation Oncology, Guro Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Republic of Korea.
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Galle PR, Tovoli F, Foerster F, Wörns MA, Cucchetti A, Bolondi L. The treatment of intermediate stage tumours beyond TACE: From surgery to systemic therapy. J Hepatol 2017; 67:173-183. [PMID: 28323121 DOI: 10.1016/j.jhep.2017.03.007] [Citation(s) in RCA: 172] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
Treatment of hepatocellular carcinoma (HCC) is dependent on the stage of the disease. Intermediate stage HCC encompasses the largest subgroup of patients with the disease, and is characterized by substantial heterogeneity. The standard therapeutic approach, transarterial chemoembolization (TACE), is probably over-used and may not be appropriate for all patients with intermediate stage HCC. In patients with extensive tumour bulk, multi-nodular spread or impaired liver function, TACE may not be optimal and other treatments can be considered as a first-line treatment. These include surgery, percutaneous ablation, radioembolization or systemic treatment. In addition, patients who do not achieve complete or partial necrosis (TACE failure) and patients with early recurrence after TACE, should be managed individually, considering systemic treatments usually reserved for advanced disease. In selected cases and in patients who achieve downstaging, radical approaches such as hepatic resection or even liver transplantation can be considered. In this review, we evaluate the current literature for the treatment strategies for patients with intermediate Barcelona Clinic Liver Cancer (BCLC) B stage HCC.
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Affiliation(s)
- Peter R Galle
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany.
| | - Francesco Tovoli
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Friedrich Foerster
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Marcus A Wörns
- University Medical Centre Mainz, I. Dept. of Internal Medicine, Langenbeckstrasse 1, 55131 Mainz, Germany
| | - Alessandro Cucchetti
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Chirurgia generale e Trapianti, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
| | - Luigi Bolondi
- Dipartimento di Scienze Mediche e Chirurgiche, Unità di Medicina Interna, Alma Mater Studiorum-Università di Bologna, Bologna, Italy
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Mori T, Ito Y, Kawabe M, Iwasaki R, Sakai H, Murakami M, Maruo K. Three-dimensional conformal radiation therapy for inoperable massive hepatocellular carcinoma in six dogs. J Small Anim Pract 2015; 56:441-5. [DOI: 10.1111/jsap.12352] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Revised: 02/16/2015] [Accepted: 02/23/2015] [Indexed: 01/15/2023]
Affiliation(s)
- T. Mori
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - Y. Ito
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - M. Kawabe
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - R. Iwasaki
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - H. Sakai
- Department of Veterinary Pathology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - M. Murakami
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
| | - K. Maruo
- Department of Veterinary Clinical Oncology, Faculty of Applied Biological Sciences; Gifu University; 1-1 Yanagido Gifu 501-1193 Japan
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Kalogeridi MA, Zygogianni A, Kyrgias G, Kouvaris J, Chatziioannou S, Kelekis N, Kouloulias V. Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review. World J Hepatol 2015; 7:101-112. [PMID: 25625001 PMCID: PMC4295187 DOI: 10.4254/wjh.v7.i1.101] [Citation(s) in RCA: 112] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Revised: 10/26/2014] [Accepted: 11/19/2014] [Indexed: 02/06/2023] Open
Abstract
Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.
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Chen D, Wang R, Meng X, Yan H, Jiang S, Feng R, Zhu K, Xu X, Dou X, Jin L. Prognostic value of serum γ-glutamyl transferase in unresectable hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization combined with conformal radiotherapy. Oncol Lett 2014; 8:2298-2304. [PMID: 25289109 PMCID: PMC4186547 DOI: 10.3892/ol.2014.2456] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 07/23/2014] [Indexed: 12/13/2022] Open
Abstract
The detection of γ-glutamyl transferase (GGT) has previously been reported to be useful in the diagnosis in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the baseline serum GGT levels in patients with intermediate HCC (Barcelona Clinic Liver Cancer stage B) following treatment with transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT). A total of 154 intermediate HCC patients with Child-Pugh grade A were retrospectively investigated. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold for the GGT serum levels, and univariate and multivariate analyses were used to establish the prognostic factors. The median overall survival (OS) time was 24.3 months. The optimal threshold for GGT was 85 U/L (sensitivity, 75.13%; specificity, 69.81%; and area under the ROC curve, 0.763). The one-, three- and five-year OS rates were 79.9, 49.7 and 17.2%, respectively, for patients with low GGT levels (≤85 U/l) and 52.3, 22.1 and 8.5%, respectively, for patients with high GGT levels (>85 U/l) (P=0.007). The results indicated that the serum GGT level was an independent prognostic factor (hazard ratio=2.32; P=0.007) for OS. Furthermore, in subgroups stratified according to serum α-fetoprotein, gross tumor volume and radiation dose, serum GGT was also found to correlate with OS (P<0.05). Therefore, the baseline GGT level may be a significant prognostic factor for intermediate HCC patients with Child-Pugh grade A following TACE combined with 3DCRT.
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Affiliation(s)
- Dong Chen
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China ; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Renben Wang
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Xiangjiao Meng
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Hongjiang Yan
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Shumei Jiang
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Rui Feng
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Kunli Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Xiaoqing Xu
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Xue Dou
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China ; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
| | - Linzhi Jin
- Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China ; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
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