|
1
|
Yariv O, Newman NB, Yarchoan M, Rabiee A, Wood BJ, Salem R, Hernandez JM, Bang CK, Yanagihara TK, Escorcia FE. Advances in radiation therapy for HCC: Integration with liver-directed treatments. Hepatol Commun 2025; 9:e0653. [PMID: 40163776 PMCID: PMC11927661 DOI: 10.1097/hc9.0000000000000653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/03/2024] [Indexed: 04/02/2025] Open
Abstract
HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.
Collapse
Affiliation(s)
- Orly Yariv
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Neil B. Newman
- Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Mark Yarchoan
- Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Atoosa Rabiee
- Division of Gastroenterology and Hepatology, Washington DC Veterans Affairs Medical Center, Washington, District of Columbia, USA
| | - Bradford J. Wood
- Interventional Radiology, Center for Interventional Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Riad Salem
- Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jonathan M. Hernandez
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Christine K. Bang
- Radiation Oncology Clinical Care Center, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA
| | - Ted K. Yanagihara
- Department of Radiation Oncology, University of North Carolina School of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA
| | - Freddy E. Escorcia
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| |
Collapse
|
|
2
|
Chen R, An Y, Xu M. Prognostic difference between surgery and external radiation in patients with stage I liver cancer based on competitive risk model and conditional survival rate. PLoS One 2024; 19:e0298014. [PMID: 38547200 PMCID: PMC10977706 DOI: 10.1371/journal.pone.0298014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 01/17/2024] [Indexed: 04/02/2024] Open
Abstract
PURPOSE This study aimed to assess the difference in prognosis of patients with early-stage liver cancer after surgery or external radiation. METHODS Between 2010 and 2015, 2155 patients with AJCC 7th stage I liver cancer were enrolled in the SEER database. Among these, 1972 patients had undergone surgery and 183 had undergone external beam radiation. The main research endpoints were overall survival (OS) and disease-specific survival (DSS). The competitive risk model was used to calculate the risk ratio of liver cancer-specific deaths when there was a competitive risk. Propensity Score Matching (PSM) method using a 1:1 ratio was used to match confounders such as sex, age, and treatment method. Conditional survival was dynamically assessed for patient survival after surgery or external radiation. RESULTS Multivariate analysis of the competitive risk model showed that age, disease diagnosis time, grade, and treatment [surgery and external beam radiation therapy (EBRT)] were independent prognostic factors for patients with hepatocellular carcinoma. Surgery had a higher survival improvement rate than that of EBRT. As the survival of patients with liver cancer increased, the survival curve of surgery declined more slowly than that of radiotherapy patients and stabilized around 3 years after surgery. The survival curve of radiotherapy patients significantly dropped within 4 years and then stabilized. CONCLUSION Surgery was better than EBRT for patients with stage I liver cancer. Close follow-up was required for 3 years after surgery or 4 years after external radiation. This study can help clinicians make better informed clinical decisions.
Collapse
Affiliation(s)
- Rong Chen
- Department of Oncology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Yanli An
- Medical School of Southeast University, Nanjing, Jiangsu Province, China
| | - Muhao Xu
- Medical School of Southeast University, Nanjing, Jiangsu Province, China
| |
Collapse
|
|
3
|
Bush DA, Volk M, Smith JC, Reeves ME, Sanghvi S, Slater JD, deVera M. Proton beam radiotherapy versus transarterial chemoembolization for hepatocellular carcinoma: Results of a randomized clinical trial. Cancer 2023; 129:3554-3563. [PMID: 37503907 DOI: 10.1002/cncr.34965] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/08/2023] [Accepted: 05/22/2023] [Indexed: 07/29/2023]
Abstract
BACKGROUND This study compares survival rates, recurrence patterns, toxicity, and treatment cost in patients with hepatocellular carcinoma (HCC) treated with either transarterial chemoembolization (TACE) or proton beam radiotherapy (PBT). METHODS Subjects with untreated HCC meeting Milan or San Francisco transplant criteria were recruited. Subjects were randomized to receive PBT (n = 36) or TACE (n = 40). Proton therapy was administered in 15 fractions over 3 weeks to a total dose of 70.2 Gy. TACE was repeated until complete or maximal response. The primary outcome measure was overall survival (OS). Secondary end points were progression-free survival (PFS), local control (LC), toxicity, and cost. RESULTS Of the 76 randomized patients, 74 were assessed for outcome measures. The 2-year OS for PBT versus TACE was similar at 68%, 95% confidence interval (CI), 0.54-0.86, and 65%, 95% CI, 0.52-0.83 (p = .80), however, median PFS was improved for PBT versus TACE (not reached vs. 12 months, p = .002). LC was improved with PBT versus TACE (hazard ratio, 5.64; 95% CI, 1.78-17.9, p = .003). Days of posttreatment hospitalization were 24 for PBT and 166 for TACE (p < .001). Total mean cost per patient for treatment and posttreatment care revealed a 28% cost savings for PBT. CONCLUSIONS PBT and TACE yielded similar OS for treatment of HCC, but PFS and LC were improved with PBT compared to TACE. Patients treated with PBT required fewer courses of treatment, fewer posttreatment hospitalization days, and reduced cost of treatment compared to TACE. These data support the use of PBT as a viable treatment alternative to TACE for patients with HCC within transplant criteria.
Collapse
Affiliation(s)
- David A Bush
- Loma Linda University Medical Center, Radiation Medicine, Loma Linda, California, USA
| | - Michael Volk
- Loma Linda University Medical Center, Transplant Institute and Liver Center, Loma Linda, California, USA
| | - Jason C Smith
- Loma Linda University Medical Center, Interventional Radiology, Loma Linda, California, USA
| | - Mark E Reeves
- Jerry L. Pettis Memorial Veterans Hospital, Loma Linda, California, USA
| | - Samrat Sanghvi
- Loma Linda University Medical Center, Radiation Medicine, Loma Linda, California, USA
| | - Jerry D Slater
- Loma Linda University Medical Center, Radiation Medicine, Loma Linda, California, USA
| | - Michael deVera
- Loma Linda University Medical Center, Transplant Institute and Liver Center, Loma Linda, California, USA
| |
Collapse
|
|
4
|
Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
| |
Collapse
|
|
5
|
2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
6
|
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Collapse
|
|
7
|
Dionisi F, Scartoni D, Fracchiolla F, Giacomelli I, Siniscalchi B, Goanta L, Cianchetti M, Sanguineti G, Brolese A. Proton therapy in the treatment of hepatocellular carcinoma. Front Oncol 2022; 12:959552. [PMID: 36003769 PMCID: PMC9393743 DOI: 10.3389/fonc.2022.959552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/13/2022] [Indexed: 12/24/2022] Open
Abstract
Liver cancer represents one of the most common causes of death from cancer worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancers. Among local therapies, evidence regarding the use of radiation therapy is growing. Proton therapy currently represents the most advanced radiation therapy technique with unique physical properties which fit well with liver irradiation. Here, in this review, we aim to 1) illustrate the rationale for the use of proton therapy (PT) in the treatment of HCC, 2) discuss the technical challenges of advanced PT in this disease, 3) review the major clinical studies regarding the use of PT for HCC, and 4) analyze the potential developments and future directions of PT in this setting.
Collapse
Affiliation(s)
- Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
- *Correspondence: Francesco Dionisi,
| | - Daniele Scartoni
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari, Trento, Italy
| | | | - Irene Giacomelli
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari, Trento, Italy
| | | | - Lucia Goanta
- Department of Advanced Biomedical Sciences, University of Naples “Federico II”, Napoli, Italy
| | - Marco Cianchetti
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari, Trento, Italy
| | - Giuseppe Sanguineti
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Alberto Brolese
- General Surgery & Hepato-Pancreato-Biliary Unit, Azienda Provinciale per i Servizi Sanitari, Trento, Italy
| |
Collapse
|
|
8
|
Kobeissi JM, Hilal L, Simone CB, Lin H, Crane CH, Hajj C. Proton Therapy in the Management of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:2900. [PMID: 35740567 PMCID: PMC9220794 DOI: 10.3390/cancers14122900] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 05/29/2022] [Accepted: 06/07/2022] [Indexed: 12/04/2022] Open
Abstract
Proton radiation therapy plays a central role in the treatment of hepatocellular carcinoma (HCC). Because of the near-zero exit dose and improved sparing of normal liver parenchyma, protons are being used even in challenging scenarios, including larger or multifocal liver tumors, and those associated with vascular tumor thrombus. There is a mounting level of evidence that suggests that protons are superior to photons in terms of survival and toxicity outcomes, specifically the progression to liver failure. A randomized controlled trial comparing protons to photons is currently underway to verify this hypothesis.
Collapse
Affiliation(s)
- Jana M. Kobeissi
- Department of Radiation Oncology, School of Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon; (J.M.K.); (L.H.)
| | - Lara Hilal
- Department of Radiation Oncology, School of Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon; (J.M.K.); (L.H.)
| | - Charles B. Simone
- New York Proton Center, Department of Radiation Oncology, New York, NY 10035, USA; (C.B.S.2nd); (H.L.)
- Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY 10027, USA;
| | - Haibo Lin
- New York Proton Center, Department of Radiation Oncology, New York, NY 10035, USA; (C.B.S.2nd); (H.L.)
| | - Christopher H. Crane
- Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY 10027, USA;
| | - Carla Hajj
- New York Proton Center, Department of Radiation Oncology, New York, NY 10035, USA; (C.B.S.2nd); (H.L.)
- Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY 10027, USA;
| |
Collapse
|
|
9
|
Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| |
Collapse
|
|
10
|
The Role of Ablative Radiotherapy to Liver Oligometastases from Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00472-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Abstract
Purpose of Review
This review describes recent data supporting locoregional ablative radiation in the treatment of oligometastatic colorectal cancer liver metastases.
Recent Findings
Stereotactic body radiotherapy (SBRT) demonstrates high rates of local control in colorectal cancer liver metastases when a biologically equivalent dose of > 100 Gy is delivered. Future innovations to improve the efficacy of SBRT include MRI-guided radiotherapy (MRgRT) to enhance target accuracy, systemic immune activation to treat extrahepatic disease, and genomic customization. Selective internal radiotherapy (SIRT) with y-90 is an intra-arterial therapy that delivers high doses to liver metastases internally which has shown to increase liver disease control in phase 3 trials. Advancements in transarterial radioembolization (TARE) dosimetry could improve local control and decrease toxicity.
Summary
SBRT and SIRT are both promising options in treating unresectable metastatic colorectal cancer liver metastases. Identification of oligometastatic patients who receive long-term disease control from either therapy is essential. Future advancements focusing on improving radiation design and customization could further improve efficacy and toxicity.
Collapse
|
|
11
|
Yoo GS, Yu JI, Park HC. Current role of proton beam therapy in patients with hepatocellular carcinoma. INTERNATIONAL JOURNAL OF GASTROINTESTINAL INTERVENTION 2021; 10:175-182. [DOI: 10.18528/ijgii210043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/09/2021] [Accepted: 10/09/2021] [Indexed: 04/24/2025] Open
Affiliation(s)
- Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
12
|
Coffman AR, Sufficool DC, Kang JI, Hsueh CT, Swenson S, McGee PQ, Nagaraj G, Patyal B, Reeves ME, Slater JD, Yang GY. Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions. J Gastrointest Oncol 2021; 12:1753-1760. [PMID: 34532125 DOI: 10.21037/jgo-20-424] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 02/01/2021] [Indexed: 12/11/2022] Open
Abstract
Background To report on our institutional experience using Proton stereotactic body radiation therapy (SBRT) for patients with liver metastases. Methods All patients with liver metastases treated with Proton SBRT between September 2012 and December 2017 were retrospectively analyzed. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method calculated from the time of completion of Proton SBRT. LC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results Forty-six patients with 81 lesions were treated with Proton SBRT. The median age was 65.5 years old (range, 33-86 years) and the median follow up was 15 months (range, 1-54 months). The median size of the gross tumor volume (GTV) was 2.5 cm (range, 0.7-8.9 cm). Two or more lesions were treated in 56.5% of patients, with one patient receiving treatment to a total of five lesions. There were 37 lesions treated with a biologically effective dose (BED) ≤60, 9 lesions with a BED of 61-80, 22 lesions with a BED of 81-100, and 13 lesions with a BED >100. The 1-year and 2-year LC for all lesions was 92.5% (95% CI, 82.7% to 96.8%). The grade 1 and grade 2 toxicity rates were 37% and 6.5%, respectively. There were no grade 3 or higher toxicities and no cases of radiation-induced liver disease (RILD). Conclusions Proton SBRT for the treatment of liver metastases has promising LC rates with the ability to safely treat multiple liver metastases. Accrual continues for our phase II trial treating liver metastases with Proton SBRT to 60 GyE (Gray equivalent) in 3 fractions.
Collapse
Affiliation(s)
- Alex R Coffman
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Daniel C Sufficool
- Department of Radiation Oncology, Kettering Health Network, Kettering, OH, USA
| | - Joseph I Kang
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Chung-Tsen Hsueh
- Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Sasha Swenson
- Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Patrick Q McGee
- Loma Linda University School of Medicine, Loma Linda, CA, USA
| | - Gayathri Nagaraj
- Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Baldev Patyal
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Mark E Reeves
- Department of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Jerry D Slater
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| | - Gary Y Yang
- Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, CA, USA
| |
Collapse
|
|
13
|
Chen LC, Lin HY, Hung SK, Chiou WY, Lee MS. Role of modern radiotherapy in managing patients with hepatocellular carcinoma. World J Gastroenterol 2021; 27:2434-2457. [PMID: 34092968 PMCID: PMC8160620 DOI: 10.3748/wjg.v27.i20.2434] [Citation(s) in RCA: 23] [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: 01/26/2021] [Revised: 04/16/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Several treatment options are available for managing HCC patients, classified roughly as local, local-regional, and systemic therapies. The high post-monotherapy recurrence rate of HCC urges the need for the use of combined modalities to increase tumor control and patient survival. Different international guidelines offer treatment recommendations based on different points of view and classification systems. Radiotherapy (RT) is a well-known local-regional treatment modality for managing many types of cancers, including HCC. However, only some of these treatment guidelines include RT, and the role of combined modalities is rarely mentioned. Hence, the present study reviewed clinical evidence for the use of different combined modalities in managing HCC, focusing on modern RT's role. Modern RT has an increased utility in managing HCC patients, mainly due to two driving forces. First, technological advancement (e.g., stereotactic body radiotherapy and advanced proton-beam therapy) enables precise delivery of radiation to increase tumor control and reduce side effects in the surrounding normal tissue. Second, the boom in developing target therapies and checkpoint-blockade immunotherapy prolongs overall survival in HCC patients, re-emphasizing the importance of local tumor control. Remarkably, RT combines with systemic therapies to generate the systemic therapy augmented by radiotherapy effect, a benefit now being actively investigated.
Collapse
Affiliation(s)
- Liang-Cheng Chen
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
| | - Hon-Yi Lin
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
- Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan
| | - Shih-Kai Hung
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Wen-Yen Chiou
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Moon-Sing Lee
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| |
Collapse
|
|
14
|
De B, Ng SP, Liu AY, Avila S, Tao R, Holliday EB, Brownlee Z, Kaseb A, Lee S, Raghav K, Vauthey JN, Minsky BD, Herman JM, Das P, Smith GL, Taniguchi CM, Krishnan S, Crane CH, Grassberger C, Hong TS, Lin SH, Koong AC, Mohan R, Koay EJ. Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy. J Hepatocell Carcinoma 2021; 8:57-69. [PMID: 33688489 PMCID: PMC7937383 DOI: 10.2147/jhc.s282062] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 02/11/2021] [Indexed: 12/14/2022] Open
Abstract
Background The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC). Patients and Methods Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy. Results Of 143 patients identified, the median age was 66 (range, 19-90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13-25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/µL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk. Conclusion Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis.
Collapse
Affiliation(s)
- Brian De
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sweet Ping Ng
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.,Department of Radiation Oncology, Austin Health, Melbourne, Victoria, Australia
| | - Amy Y Liu
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Santiago Avila
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Randa Tao
- Department of Radiation Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Emma B Holliday
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zachary Brownlee
- Department of Radiation Oncology, Tufts Medical Center, Boston, MA, USA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sunyoung Lee
- Department of Radiation Oncology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Joseph M Herman
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Grace L Smith
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cullen M Taniguchi
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, USA
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Clemens Grassberger
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Steven H Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Albert C Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Radhe Mohan
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
15
|
Mortensen HR, Villadsen GE, Worm ES, Weber B. Survival and morbidity following stereotactic radiotherapy of hepatocellular carcinoma: a ten-year, single institution experience. Scand J Gastroenterol 2021; 56:259-265. [PMID: 33430663 DOI: 10.1080/00365521.2020.1869822] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option in hepatocellular carcinoma (HCC) in patients ineligible for other local ablative therapies. This study reports on the safety and efficacy of SABR in a Danish cohort of HCC patients. MATERIALS AND METHODS Between January 2009 and December 2018, 28 patients with HCCs were treated with SABR at our institution. The primary endpoint of this retrospective study was local control; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS In 28 patients, 32 tumors (median size 3.7 cm, range 1.4-6.8 cm) were treated. The median follow-up time was 16 months. Most patients (68%) received previous liver-directed treatments. A dose of 48 Gy in three or six fractions were given to 43% of the patients. Grad 1 or 2 toxicity was reported in 13 patients (46%), whereas 4 patients (14%) needed hospitalization (grade 3). One-year local control and overall survivals were 90% and 71%, respectively. One-year progression-free survival was 32%, and 65% of patients with disease progression received further HCC therapy. In univariate analysis, none of the examined factors predicted recurrence or overall survival. CONCLUSION SABR provides high local control to inoperable HCC. SABR can be delivered safely even after previous liver-directed therapies and subsequent therapies are feasible after treatment with SABR. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximize disease control.
Collapse
Affiliation(s)
- Hanna Rahbek Mortensen
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.,Danish Center of Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
| | | | - Esben Schjødt Worm
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | - Britta Weber
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.,Danish Center of Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
|
16
|
Mahmoud D, Mohammed MA, Zeidan Y, Shamseddine A. Radiotherapy for Hepatocellular Carcinoma. LIVER CANCER IN THE MIDDLE EAST 2021:189-200. [DOI: 10.1007/978-3-030-78737-0_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
17
|
Kumari S, Mukherjee S, Sinha D, Abdisalaam S, Krishnan S, Asaithamby A. Immunomodulatory Effects of Radiotherapy. Int J Mol Sci 2020; 21:E8151. [PMID: 33142765 PMCID: PMC7663574 DOI: 10.3390/ijms21218151] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/22/2020] [Accepted: 10/26/2020] [Indexed: 02/07/2023] Open
Abstract
Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.
Collapse
Affiliation(s)
- Sharda Kumari
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (S.K.); (D.S.); (S.A.)
| | - Shibani Mukherjee
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (S.K.); (D.S.); (S.A.)
| | - Debapriya Sinha
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (S.K.); (D.S.); (S.A.)
| | - Salim Abdisalaam
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (S.K.); (D.S.); (S.A.)
| | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA;
| | - Aroumougame Asaithamby
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; (S.K.); (D.S.); (S.A.)
| |
Collapse
|
|
18
|
Dionisi F, Brolese A, Siniscalchi B, Giacomelli I, Fracchiolla F, Righetto R, Morganti AG, Pravadelli C, Avancini I, Rozzanigo U, Mattiuzzi A, Frisinghelli M, Pertile R, Ciarleglio FA, Vitale A, Schwarz M, Amichetti M. Clinical results of active scanning proton therapy for primary liver tumors. TUMORI JOURNAL 2020; 107:71-79. [PMID: 32648818 DOI: 10.1177/0300891620937809] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Evidence for the efficacy of radiation therapy for primary liver cancer is growing. In this context, proton therapy (PT) can potentially improve the therapeutic ratio, as demonstrated by recent clinical studies. Here we report the first European clinical experience on the use of PT for primary liver cancer. METHODS All patients treated for primary liver cancer in our center entered the analysis. Patients were simulated during deep expiration breath-hold. A 15-fraction treatment schedule was adopted using active scanning PT. Clinical outcome and toxicity were retrospectively analyzed. RESULTS Between January 2018 and December 2019, 18 patients were treated. Fourteen patients had hepatocellular carcinoma (HCC), three patients had intrahepatic cholangiocarcinoma (ICC), and one patient had synchronous ICC-HCC. The Child-Pugh score was A5 in the majority of patients with HCC (71.4%). Median prescription dose was 58.05 Gy (range, 50.31-67.5). Median follow-up was 10 months (range, 1-19). The majority of deaths occurred from liver tumor progression. One-year overall survival (OS) was 63%. A significant correlation between worse OS and patient performance status, vascular invasion, and tumor stage was recorded. One-year local control was 90%. Toxicity was low, with a decrease in Child-Pugh score ⩾2 points detected in one patient. No cases of classic radiation-induced liver disease occurred. CONCLUSIONS Our initial results of active scanning PT for primary liver cancer demonstrated the feasibility, safety, and effectiveness of this advanced technique in this setting. The potential of the combination of PT with other locoregional therapies is under evaluation.
Collapse
Affiliation(s)
- Francesco Dionisi
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | | | | | - Irene Giacomelli
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | - Francesco Fracchiolla
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | - Roberto Righetto
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | | | | | - Ivo Avancini
- Gastroenterology Department, APSS, Trento, Italy
| | | | | | | | | | | | - Alessandro Vitale
- Department of Surgical, Oncological & Gastroenterological Sciences, Padua University Hospital, Italy
| | - Marco Schwarz
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy.,Trento Insitute for Fundamental Physics and Applications, TIFPA, National Institute for Nuclaer Physics, INFN, Trento, Italy
| | - Maurizio Amichetti
- Proton Therapy Unit, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| |
Collapse
|
|
19
|
Siddiqui O, Pollock A, Samanta S, Kaiser A, Molitoris JK. Proton Beam Therapy in Liver Malignancies. Curr Oncol Rep 2020; 22:30. [PMID: 32108284 DOI: 10.1007/s11912-020-0889-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Proton beam therapy (PBT) allows for improved sparing of surrounding normal tissues compared with X-ray-based radiation therapy. This is especially important in the setting of liver malignancies, where an increase in integral dose leads to a higher risk of radiation-induced liver disease (RILD) as well as close proximity to vital gastrointestinal (GI) organs. RECENT FINDINGS We have data from multiple centers demonstrating that PBT can safely deliver high, ablative doses of radiation therapy conferring excellent local control with good tolerance of treatment. PBT is an effective treatment with longstanding evidence of efficacy that is increasing in availability.
Collapse
Affiliation(s)
- Osman Siddiqui
- Department of Radiation Oncology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD, 21201, USA
| | - Ariel Pollock
- Department of Radiation Oncology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD, 21201, USA
| | - Santanu Samanta
- Department of Radiation Oncology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD, 21201, USA
| | - Adeel Kaiser
- Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD, 21201, USA
| | - Jason K Molitoris
- Department of Radiation Oncology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD, 21201, USA.
| |
Collapse
|
|
20
|
Abou-Alfa GK, Jarnagin W, El Dika I, D'Angelica M, Lowery M, Brown K, Ludwig E, Kemeny N, Covey A, Crane CH, Harding J, Shia J, O'Reilly EM. Liver and Bile Duct Cancer. ABELOFF'S CLINICAL ONCOLOGY 2020:1314-1341.e11. [DOI: 10.1016/b978-0-323-47674-4.00077-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
21
|
Novel Radiotherapy Technologies in the Treatment of Gastrointestinal Malignancies. Hematol Oncol Clin North Am 2019; 34:29-43. [PMID: 31739949 DOI: 10.1016/j.hoc.2019.08.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Over the past 2 decades, major technical advances in radiation therapy planning and delivery have made it possible to deliver higher doses to select high-risk volumes. This has helped to expand the role of radiation therapy in the treatment of gastrointestinal malignancies. Whereas dose escalation was previously limited by the radiosensitivity of normal tissues within and adjacent to the gastrointestinal tract, advances in target delineation, patient immobilization, treatment planning, and image-guided treatment delivery have greatly improved the therapeutic ratio. More conformal radiation modalities can offer further dose optimization to target volumes while sparing normal tissue from toxicity.
Collapse
|
|
22
|
A comparison of the outcomes between surgical resection and proton beam therapy for single primary hepatocellular carcinoma. Surg Today 2019; 50:369-378. [PMID: 31602531 DOI: 10.1007/s00595-019-01888-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/13/2019] [Indexed: 12/22/2022]
Abstract
PURPOSE There are many treatment choices for hepatocellular carcinoma (HCC), one of which is proton beam therapy (PBT). The purpose of this study was to compare surgical resection (SR) and PBT to clarify the prognostic factors for operable HCC based on a single institution's database. METHODS Patients with single primary nodular HCC ≤ 100 mm without vessel invasion on pretreatment imaging were divided into the SR group and PBT group. In the PBT group, the patients with unresectable HCC due to their liver function and/or performance status were excluded. RESULTS There were 314 and 31 patients who underwent SR and PBT, respectively. The median survival time in the SR group was significantly better than in the PBT group (104.1 vs. 64.6 months, p = 0.008). Regarding the relapse-free survival (RFS), there was no significant difference between the SR and PBT groups (33.8 vs. 14.0 months, p = 0.099). CONCLUSION The RFS was comparable between the PBT and SR groups. However, the PBT group had a significantly worse overall survival than the SR group. SR may therefore be favorable as an initial treatment for HCC compared to PBT.
Collapse
|
|
23
|
Hojo H, Raturi V, Nakamura N, Arahira S, Akita T, Mitsunaga S, Nakamura M, Motegi A, Kageyama SI, Zenda S, Okumura M, Ikeda M, Akimoto T. Impact of Proton Beam Irradiation of an Anatomic Subsegment of the Liver for Hepatocellular Carcinoma. Pract Radiat Oncol 2019; 10:e264-e271. [PMID: 31585204 DOI: 10.1016/j.prro.2019.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 09/12/2019] [Accepted: 09/24/2019] [Indexed: 10/25/2022]
Abstract
PURPOSE The objective of this research was to elucidate the impact on the prognosis, including the survival prognosis, resulting from proton beam irradiation of an anatomic subsegment of the liver (ASPT) for the treatment of hepatocellular carcinoma (HCC). METHODS AND MATERIALS A total of 110 patients who received a diagnosis of HCC were analyzed in this retrospective study. Definitive proton beam therapy was delivered at a dose of 76 Gy (relative biological effectiveness) in 20 fractions between January 2008 and December 2015. When the HCC widely abutted blood vessels or when multiple HCC tumors occurred within the same liver subsegment, the clinical target volume was outlined as an anatomic subsegment of the liver, according to the portal territory, containing the tumor. In the remaining cases, the clinical target volume was delineated by adding a 5-mm margin around the gross tumor volume. The overall survival (OS), progression-free survival (PFS), and local control rates and adverse events were assessed. A review of the medical charts assessed adverse events that occurred during and after the treatment and were classified according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS The median follow-up duration was 36.5 months (range, 1-90.6 months). The median age of the patients was 73 years (range, 48-90 years). ASPT was performed in 31 patients (28%). Three-year OS, PFS, and local control rates were 74.2%, 40.4%, and 91.7%, respectively. Multivariate analysis identified ASPT as a factor that significantly improved PFS (P = .049) but not OS (P = .79). No association was found between ASPT and the frequency of grade ≥3 acute/late adverse events. CONCLUSIONS ASPT was associated with a reduction in the rate of tumor progression and no significant toxicity but was not associated with OS.
Collapse
Affiliation(s)
- Hidehiro Hojo
- Division of Radiation Oncology and Particle Therapy.
| | - Vijay Raturi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
| | | | | | | | - Shuichi Mitsunaga
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
| | | | | | | | | | | | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan
| | | |
Collapse
|
|
24
|
In Reply to Tsang et al. Int J Radiat Oncol Biol Phys 2019; 105:231. [DOI: 10.1016/j.ijrobp.2019.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 03/04/2019] [Accepted: 03/04/2019] [Indexed: 11/20/2022]
|
|
25
|
Raldow A, Lamb J, Hong T. Proton beam therapy for tumors of the upper abdomen. Br J Radiol 2019; 93:20190226. [PMID: 31430202 DOI: 10.1259/bjr.20190226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Proton radiotherapy has clear dosimetric advantages over photon radiotherapy. In contrast to photons, which are absorbed exponentially, protons have a finite range dependent on the initial proton energy. Protons therefore do not deposit dose beyond the tumor, resulting in great conformality, and offers the promise of dose escalation to increase tumor control while minimizing toxicity. In this review, we discuss the rationale for using proton radiotherapy in the treatment of upper abdominal tumors-hepatocellular carcinomas, cholangiocarcinomas and pancreatic cancers. We also review the clinical outcomes and technical challenges of using proton radiotherapy for the treatment of these malignancies. Finally, we discuss the ongoing clinical trials implementing proton radiotherapy for the treatment of primary liver and pancreatic tumors.
Collapse
Affiliation(s)
- Ann Raldow
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - James Lamb
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Theodore Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| |
Collapse
|
|
26
|
Hsu CY, Wang CW, Cheng AL, Kuo SH. Hypofractionated particle beam therapy for hepatocellular carcinoma-a brief review of clinical effectiveness. World J Gastrointest Oncol 2019; 11:579-588. [PMID: 31435460 PMCID: PMC6700034 DOI: 10.4251/wjgo.v11.i8.579] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/22/2019] [Accepted: 07/16/2019] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer mortality worldwide. The cornerstone to improving the prognosis of HCC patients has been the control of loco-regional disease progression and the lesser toxicities of local treatment. Although radiotherapy has not been considered a preferred treatment modality for HCC, charged particle therapy (CPT), including proton beam therapy (PBT) and carbon ion radiotherapy (CIRT), possesses advantages (for example, it allows ablative radiation doses to be applied to tumors but simultaneously spares the normal liver parenchyma from radiation) and has emerged as an alternative treatment option for HCC. With the technological advancements in CPT, various radiation dosages of CPT have been used for HCC treatment via CPT. However, the efficacy and safety of the evolving dosages remain uncertain. To assess the association between locoregional control of HCC and the dose and regimen of CPT, we provide a brief overview of selected literature on dose regimens from conventional to hypofractionated short-course CPT in the treatment of HCC and the subsequent determinants of clinical outcomes. Overall, CPT provides a better local control rate compared with photon beam therapy, ranging from 80% to 96%, and a 3-year overall survival ranging from 50% to 75%, and it results in rare grade 3 toxicities of the late gastrointestinal tract (including radiation-induced liver disease). Regarding CPT for the treatment of locoregional HCC, conventional CPT is preferred to treat central tumors of HCC to avoid late toxicities of the biliary tract. In contrast, the hypo-fractionation regimen of CPT is suggested for treatment of larger-sized tumors of HCC to overcome potential radio-resistance.
Collapse
Affiliation(s)
- Che-Yu Hsu
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Chun-Wei Wang
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
| | - Ann-Lii Cheng
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Department of Internal Medicine and Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Sung-Hsin Kuo
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
- National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Cancer Research Center, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei 100, Taiwan
| |
Collapse
|
|
27
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
28
|
Sayan M, Yegya-Raman N, Greco SH, Gui B, Zhang A, Chundury A, Grandhi MS, Hochster HS, Kennedy TJ, Langan RC, Malhotra U, Rustgi VK, Shah MM, Spencer KR, Carpizo DR, Nosher JL, Jabbour SK. Rethinking the Role of Radiation Therapy in the Treatment of Unresectable Hepatocellular Carcinoma: A Data Driven Treatment Algorithm for Optimizing Outcomes. Front Oncol 2019; 9:345. [PMID: 31275846 PMCID: PMC6591511 DOI: 10.3389/fonc.2019.00345] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Accepted: 04/15/2019] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, with a majority of HCC patients not suitable for curative therapies. Approximately 70% of initially diagnosed patients cannot undergo surgical resection or transplantation due to locally advanced disease, poor liver function/underlying cirrhosis, or additional comorbidities. Local therapeutic options for patients with unresectable HCC, who are not suitable for thermal ablation, include transarterial embolization (bland, chemoembolization, radioembolization) and/or external beam radiation therapy (EBRT). Regarding EBRT specifically, technological advancements provide a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In multiple prospective studies, EBRT delivery in a variety of different fractionation schemes or in combination with transcatheter arterial chemoembolization (TACE) demonstrate improved outcomes, particularly with combination therapy. The Barcelona Clinic Liver Cancer classification provides a framework for treatment selection; however, given the growing complexity of treatment strategies, this classification system tends to simplify decision-making. In this review, we discuss the current literature regarding unresectable HCC and propose a modified treatment algorithm that emphasizes the role of radiation therapy for Child-Pugh score A or B patients with ≤3 nodules measuring >3 cm, multinodular disease or portal venous thrombosis.
Collapse
Affiliation(s)
- Mutlay Sayan
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Nikhil Yegya-Raman
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Stephanie H. Greco
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Bin Gui
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Andrew Zhang
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Anupama Chundury
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Miral S. Grandhi
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Howard S. Hochster
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States
| | - Timothy J. Kennedy
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Russell C. Langan
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Usha Malhotra
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States
| | - Vinod K. Rustgi
- Division of Gastroenterology and Hepatology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Mihir M. Shah
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, United States
| | - Kristen R. Spencer
- Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, United States
| | - Darren R. Carpizo
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - John L. Nosher
- Department of Radiology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| | - Salma K. Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, United States
| |
Collapse
|
|
29
|
2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
Collapse
|
|
30
|
Komatsu S, Terashima K, Matsuo Y, Takahashi D, Suga M, Nishimura N, Lee D, Tai K, Kido M, Toyama H, Demizu Y, Tokumaru S, Okimoto T, Sasaki R, Fukumoto T. Validation of combination treatment with surgical spacer placement and subsequent particle radiotherapy for unresectable hepatocellular carcinoma. J Surg Oncol 2019; 120:214-222. [PMID: 31075183 DOI: 10.1002/jso.25495] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/12/2019] [Accepted: 04/20/2019] [Indexed: 11/11/2022]
Affiliation(s)
- Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kazuki Terashima
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Yoshiro Matsuo
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Daiki Takahashi
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Masaki Suga
- Department of Radiation Physics, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Naoko Nishimura
- Department of Radiation Technology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Dongha Lee
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kentaro Tai
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yusuke Demizu
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan.,Department of Radiation Oncology, Hyogo Ion Beam Medical Center Kobe Proton Center, Kobe, Hyogo, Japan
| | - Sunao Tokumaru
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Tomoaki Okimoto
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Ryohei Sasaki
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| |
Collapse
|
|
31
|
Shibuya K, Ohno T, Katoh H, Okamoto M, Shiba S, Koyama Y, Kakizaki S, Shirabe K, Nakano T. A feasibility study of high-dose hypofractionated carbon ion radiation therapy using four fractions for localized hepatocellular carcinoma measuring 3 cm or larger. Radiother Oncol 2019; 132:230-235. [PMID: 30366726 DOI: 10.1016/j.radonc.2018.10.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 09/18/2018] [Accepted: 10/08/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND PURPOSE To evaluate the safety of carbon-ion radiotherapy (C-ion RT) using 60 Gy (relative biological effectiveness, RBE) in four fractions for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS The primary outcome was acute toxicities within 90 days. The secondary outcomes were late toxicities, local control, and progression-free survival and overall survival rates. The key inclusion criteria were as follows: (1) 3 cm or larger HCC without major vascular invasion and not adjacent to the alimentary tract; (2) Child-Pugh's grade A/B; and (3) without extrahepatic metastasis. RESULTS A total of 21 cases were analyzed between October 2012 and April 2016. The median follow-up period among the 17 survivors was 24.2 (range: 6.3-43.7) months. Grade 3 or higher acute toxicity was not observed, while three (14.3%) of the 21 patients experienced grade 3 late toxicities. The 1- and 2-year local control, progression-free survival, and overall survival rates were 100% and 92.3%, 81.0% and 50.0%, and 90.5% and 80.0%, respectively. CONCLUSION C-ion RT using 60 Gy (RBE) in four fractions was safe and achieved promising local tumor control.
Collapse
Affiliation(s)
- Kei Shibuya
- Gunma University Heavy Ion Medical Center, Maebashi, Japan; Department of Radiation Oncology, Gunma University Hospital, Maebashi, Japan.
| | - Tatsuya Ohno
- Gunma University Heavy Ion Medical Center, Maebashi, Japan
| | - Hiroyuki Katoh
- Gunma University Heavy Ion Medical Center, Maebashi, Japan
| | | | - Shintaro Shiba
- Department of Radiation Oncology, Gunma University Hospital, Maebashi, Japan
| | - Yoshinori Koyama
- Department of Radiology, National Hospital Organization Shibukawa Medical Center, Japan
| | - Satoru Kakizaki
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Ken Shirabe
- Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Takashi Nakano
- Gunma University Heavy Ion Medical Center, Maebashi, Japan; Department of Radiation Oncology, Gunma University Hospital, Maebashi, Japan
| |
Collapse
|
|
32
|
Hsieh CE, Venkatesulu BP, Lee CH, Hung SP, Wong PF, Aithala SP, Kim BK, Rao A, Tung-Chieh Chang J, Tsang NM, Wang CC, Lee CC, Lin CC, Tseng JH, Chou WC, Wang YC, Krishnan S, Hong JH. Predictors of Radiation-Induced Liver Disease in Eastern and Western Patients With Hepatocellular Carcinoma Undergoing Proton Beam Therapy. Int J Radiat Oncol Biol Phys 2019; 105:73-86. [PMID: 30797890 DOI: 10.1016/j.ijrobp.2019.02.032] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 02/03/2019] [Accepted: 02/11/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE To identify predictors of radiation-induced liver disease (RILD) in patients with hepatocellular carcinoma (HCC) treated with proton beam therapy (PBT). METHODS This multicenter study included 136 patients with HCC (eastern, n = 102; western, n = 34) without evidence of intrahepatic tumor progression after PBT. The RILD was defined as ascites with alkaline-phosphatase abnormality, grade ≥3 hepatic toxicity, or Child-Pugh score worsening by ≥2 within 4 months after PBT completion. The proton doses were converted to equivalent doses in 2-GyE fractions. The unirradiated liver volume (ULV) was defined as the absolute liver volume (LV) receiving <1 GyE; the standard liver volume (SLV) was calculated using body surface area. Possible correlations of clinicodosimetric parameters with RILD were examined. RESULTS The mean pretreatment LV was 85% of SLV, and patients with a history of hepatectomy (P < .001) or hepatitis B virus infection (P = .035) had significantly smaller LV/SLV. Nineteen (14%) patients developed RILD. Multivariate logistic regression analysis identified ULV/SLV (P = .001), gross tumor volume (P = .001), and Child-Pugh classification (P = .002) as independent RILD predictors, and mean liver dose and target-delivered dose were not associated with RILD occurrence. A "volume-response" relationship between ULV/SLV and RILD was consistently observed in both eastern and western cohorts. In Child-Pugh class-A patients whose ULV/SLV were ≥50%, 49.9%-40%, 39.9%-30% and <30%, the RILD incidences were 0%, 6%, 16%, and 39% (P < .001), respectively. For the Child-Pugh class-B group, the RILD incidences in patients with ≥60%, 59.9%-40%, and <40% of ULV/SLV were 0%, 14%, and 83% (P = .006), respectively. CONCLUSIONS The ULV/SLV, not mean liver dose, independently predicts RILD in patients with HCC undergoing PBT. The relative and absolute contraindications for Child-Pugh class-A patient's ULV/SLV are <50% and <30%, and <60% and <40% for Child-Pugh class-B patients, respectively. Our results indicate that the likelihood of hepatic complications for PBT is dictated by similar metrics as that for surgery.
Collapse
Affiliation(s)
- Cheng-En Hsieh
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China; Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; The University of Texas MD Anderson Cancer Center-UT Health Graduate School of Biomedical Sciences, Houston, Texas
| | - Bhanu Prasad Venkatesulu
- Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ching-Hsin Lee
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Sheng-Ping Hung
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Pei-Fong Wong
- Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sathvik Panambur Aithala
- Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Byung Kyu Kim
- Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; The University of Texas MD Anderson Cancer Center-UT Health Graduate School of Biomedical Sciences, Houston, Texas
| | - Arvind Rao
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
| | - Joseph Tung-Chieh Chang
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China; School of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Chun-Chieh Wang
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China; Department of Medical Imaging and Radiological Science, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Chung-Chi Lee
- Department of Medical Imaging and Radiological Science, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Jeng-Hwei Tseng
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Wen-Chi Chou
- Department of Medical Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Yu-Chao Wang
- Department of Surgery, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China
| | - Sunil Krishnan
- Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; The University of Texas MD Anderson Cancer Center-UT Health Graduate School of Biomedical Sciences, Houston, Texas; Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ji-Hong Hong
- Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China; Department of Institute for Radiological Research, Chang Gung Memorial Hospital, Linkou and College of Medicine, Chang Gung University, Taoyuan City, Taiwan, China.
| |
Collapse
|
|
33
|
Sanford NN, Pursley J, Noe B, Yeap BY, Goyal L, Clark JW, Allen JN, Blaszkowsky LS, Ryan DP, Ferrone CR, Tanabe KK, Qadan M, Crane CH, Koay EJ, Eyler C, DeLaney TF, Zhu AX, Wo JY, Grassberger C, Hong TS. Protons versus Photons for Unresectable Hepatocellular Carcinoma: Liver Decompensation and Overall Survival. Int J Radiat Oncol Biol Phys 2019; 105:64-72. [PMID: 30684667 DOI: 10.1016/j.ijrobp.2019.01.076] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 12/29/2018] [Accepted: 01/13/2019] [Indexed: 12/23/2022]
Abstract
PURPOSE Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC. METHODS AND MATERIALS This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date. RESULTS The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons. CONCLUSIONS Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC.
Collapse
Affiliation(s)
- Nina N Sanford
- Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Pursley
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Bridget Noe
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Beow Y Yeap
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Lipika Goyal
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jeffrey W Clark
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jill N Allen
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | | | - David P Ryan
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Christopher H Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Eugene J Koay
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas
| | - Christine Eyler
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Thomas F DeLaney
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrew X Zhu
- Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Clemens Grassberger
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
| |
Collapse
|
|
34
|
Apisarnthanarax S, Bowen SR, Combs SE. Proton Beam Therapy and Carbon Ion Radiotherapy for Hepatocellular Carcinoma. Semin Radiat Oncol 2018; 28:309-320. [PMID: 30309641 DOI: 10.1016/j.semradonc.2018.06.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Charged particle therapy with proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) has emerged as a promising radiation modality to minimize radiation hepatotoxicity while maintaining high rates of tumor local control. Both PBT and CIRT deposit the majority of their dose at the Bragg peak with little to no exit dose, resulting in superior sparing of normal liver tissue. CIRT has an additional biological advantage of increased relative biological effectiveness, which may allow for increased hypofractionation regimens. Retrospective and prospective studies have demonstrated encouragingly high rates of local control and overall survival and low rates of hepatotoxicity with PBT and CIRT. Ongoing randomized trials will evaluate the value of PBT over photons and other standard liver-directed therapies and future randomized trials are needed to assess the value of CIRT over PBT.
Collapse
Affiliation(s)
| | - Stephen R Bowen
- Departments of Radiation Oncology and Radiology, University of Washington, Seattle, WA
| | - Stephanie E Combs
- Department of Radiation Oncology, University Hospital Rechts der Isar, Technical University München, Munich, Germany; Institute of Innovative Radiotherapy, Helmholtzzentrum München, Munich, Germany
| |
Collapse
|
|
35
|
Shibuya K, Ohno T, Terashima K, Toyama S, Yasuda S, Tsuji H, Okimoto T, Shioyama Y, Nemoto K, Kamada T, Nakano T. Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi-institutional retrospective study. Liver Int 2018; 38:2239-2247. [PMID: 30240527 DOI: 10.1111/liv.13969] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 08/21/2018] [Accepted: 09/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Carbon-ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single-centre studies. We evaluated the effectiveness and safety of short-course carbon-ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. METHODS Consecutive hepatocellular carcinoma patients who were treated with carbon-ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment-related toxicity and radiation-induced liver disease. RESULTS A total of 174 patients were included in this study. Prescribed carbon-ion radiation therapy doses were (relative biological effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0 Gy (n = 20) in four fractions. The median follow-up period was 20.3 (range, 2.9-103.5) months. The overall survival and local control rates at 1, 2 and 3 years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1-2, Child-Pugh class B, maximum tumour diameter ≥3 cm, multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant prognostic factors of overall survival. No treatment-related death occurred during the follow-up period. Grades 3 or 4 treatment-related toxicities were observed in 10 patients (5.7%); radiation-induced liver disease was observed in three patients (1.7%). CONCLUSIONS Short-course carbon-ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma.
Collapse
Affiliation(s)
- Kei Shibuya
- Gunma University Heavy Ion Medical Center, Maebashi, Japan
| | - Tatsuya Ohno
- Gunma University Heavy Ion Medical Center, Maebashi, Japan
| | - Kazuki Terashima
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Japan
| | - Shingo Toyama
- Ion Beam Therapy Center, SAGA-HIMAT Foundation, Tosu, Japan
| | - Shigeo Yasuda
- National Institute of Radiological Science Hospital, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan
| | - Hiroshi Tsuji
- National Institute of Radiological Science Hospital, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan
| | - Tomoaki Okimoto
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Japan
| | | | - Kenji Nemoto
- Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Tadashi Kamada
- National Institute of Radiological Science Hospital, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan
| | - Takashi Nakano
- Gunma University Heavy Ion Medical Center, Maebashi, Japan
| | | |
Collapse
|
|
36
|
|
|
37
|
Huang Y, Hidaka M, Takatsuki M, Soyama A, Adachi T, Ono S, Kugiyama T, Hara T, Okada S, Yoshimoto T, Hamada T, Eguchi S. Surgical findings and technical knacks to performing living donor liver transplantation for hepatocellular carcinoma recurrence after carbon ion radiotherapy. J Surg Case Rep 2018; 2018:rjy228. [PMID: 30151117 PMCID: PMC6105107 DOI: 10.1093/jscr/rjy228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 07/31/2018] [Accepted: 08/06/2018] [Indexed: 11/18/2022] Open
Abstract
Although carbon-ion radiotherapy (CIRT) has been reported to achieve good local control of hepatocellular carcinoma (HCC), liver transplantation is still required in patients with tumor recurrence. However, few cases of living donor liver transplantation (LDLT) after curative CIRT for HCC has been reported. It would be of great interest to ascertain the true situation of the irradiated region as well as to clarify the surgical points. We herein report the surgical findings and our experience along with technical difficulties and knacks concerning two cases of LDLT for HCC after CIRT. Both patients suffered tumor recurrence after curative CIRT for HCC. Severe adhesions were found between the irradiated region and the surrounding tissues, which resulted in surgical difficulties. Histological findings showed severe tissue fibrosis in the CIRT area. We should pay attention to adhesions in the irradiated area caused by CIRT including the vascular reconstruction during surgery.
Collapse
Affiliation(s)
- Yu Huang
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Shinichiro Ono
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tota Kugiyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Satomi Okada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoko Yoshimoto
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takashi Hamada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| |
Collapse
|
|
38
|
Yoo GS, Yu JI, Park HC. Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives. World J Gastroenterol 2018; 24:3090-3100. [PMID: 30065555 PMCID: PMC6064962 DOI: 10.3748/wjg.v24.i28.3090] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/28/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, as few patients can be treated with currently available curative local modalities. In patients with HCC where curative modalities are not feasible, radiation therapy (RT) has emerged as an alternative or combination therapy. With the development of various technologies, RT has been increasingly used for the management of HCC. Among these advances, proton beam therapy (PBT) has several unique physical properties that give it a finite range in a distal direction, and thus no exit dose along the beam path. Therefore, PBT has dosimetric advantages compared with X-ray therapy for the treatment of HCC. Indeed, various reports in the literature have described the favorable clinical outcomes and improved safety of PBT for HCC patients compared with X-ray therapy. However, there are some technical issues regarding the use of PBT in HCC, including uncertainty of organ motion and inaccuracy during calculation of tissue density and beam range, all of which may reduce the robustness of a PBT treatment plan. In this review, we discuss the physical properties, current clinical data, technical issues, and future perspectives on PBT for the treatment of HCC.
Collapse
Affiliation(s)
- Gyu Sang Yoo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea
- Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea
| |
Collapse
|
|
39
|
McDuff SGR, Remillard KA, Zheng H, Raldow AC, Wo JY, Eyler CE, Drapek LC, Goyal L, Blaszkowsky LS, Clark JW, Allen JN, Parikh AR, Ryan DP, Ferrone CR, Tanabe KK, Wolfgang JA, Zhu AX, Hong TS. Liver reirradiation for patients with hepatocellular carcinoma and liver metastasis. Pract Radiat Oncol 2018; 8:414-421. [PMID: 29937235 DOI: 10.1016/j.prro.2018.04.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 03/27/2018] [Accepted: 04/18/2018] [Indexed: 01/20/2023]
Abstract
PURPOSE This study aimed to assess the safety and efficacy of administering liver reirradiation to patients with primary liver tumors or liver metastasis. METHODS AND MATERIALS A total of 49 patients (with 64 individual tumors) who received liver reirradiation at our institution between June 2008 and December 2016 were identified for retrospective review. Patients were treated to the same, different, or a combination of previously treated liver tumors for recurrent primary (53%) or metastatic (47%) disease using photons or protons. Clinical and treatment-related factors were compiled and patients were monitored for toxicity and evidence of classic or nonclassic radiation-induced liver disease. Survival was estimated with the Kaplan-Meier method and cumulative incidence of local failure (LF) was used to estimate LF using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS The median age at the time of reirradiation was 72 years and the median interval between radiation courses was 9 months. At a median follow-up of 10.5 months, 36 patients (73%) had died, 9 patients (18%) were alive, and 4 patients (8%) were lost to follow-up. The median survival for the cohort was 14 months. The overall 1-year estimate of LF was 46.4%. The 1-year estimates of LF for liver metastases and hepatocellular carcinoma were 61.0% and 32.5%, respectively. The average prescription dose was similar between the reirradiation and initial courses (equivalent dose in 2 Gy fractions EQD2: 65.0 vs 64.3 Gyα/β = 10, respectively) but the average dose to the untreated liver was lower at the time of reirradiation (EQD2: 10.5 vs 13.9 Gyα/β = 3, respectively, P = .01). Among patients with hepatocellular carcinoma, the average normal liver dose was significantly larger for patients who exhibited a worsening of Child-Pugh score after reirradiation compared with those who did not (1210 cGy vs 759 cGy, P = .04). With regard to toxicity, 85.7% of patients experienced grade 1 to 2 toxicity, 4.1% developed grade 3, and only 2 patients (4.1%) met the criteria for radiation-induced liver disease after reirradiation. CONCLUSIONS Liver reirradiation may be an effective and safe option for select patients; however, further prospective study is necessary to establish treatment guidelines and recommended dosing.
Collapse
Affiliation(s)
- Susan G R McDuff
- Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts; Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
| | - Kyla A Remillard
- Department of Radiation Oncology, Medical Physics and Dosimetry, Massachusetts General Hospital, Boston, Massachusetts
| | - Hui Zheng
- Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Ann C Raldow
- Department of Radiation Oncology, Ronald Reagan UCLA Medical Center, Los Angeles, California
| | - Jennifer Y Wo
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Christine E Eyler
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Lorraine C Drapek
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Lipika Goyal
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Lawrence S Blaszkowsky
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jeffrey W Clark
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Jill N Allen
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Aparna R Parikh
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - David P Ryan
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Department of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - John A Wolfgang
- Department of Radiation Oncology, Medical Physics and Dosimetry, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrew X Zhu
- Department of Internal Medicine and Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| |
Collapse
|
|
40
|
Mizuhata M, Takamatsu S, Shibata S, Bou S, Sato Y, Kawamura M, Asahi S, Tameshige Y, Maeda Y, Sasaki M, Kumano T, Kobayashi S, Yamamoto K, Tamamura H, Gabata T. Respiratory-gated Proton Beam Therapy for Hepatocellular Carcinoma Adjacent to the Gastrointestinal Tract without Fiducial Markers. Cancers (Basel) 2018; 10:cancers10020058. [PMID: 29466294 PMCID: PMC5836090 DOI: 10.3390/cancers10020058] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 02/16/2018] [Accepted: 02/19/2018] [Indexed: 12/14/2022] Open
Abstract
The efficacy of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) has been reported, but insertion of fiducial markers in the liver is usually required. We evaluated the efficacy and toxicity of respiratory-gated PBT without fiducial markers for HCC located within 2 cm of the gastrointestinal tract. From March 2011 to December 2015 at our institution, 40 patients were evaluated (median age, 72 years; range, 38-87 years). All patients underwent PBT at a dose of 60 to 80 cobalt gray equivalents (CGE) in 20 to 38 fractions. The median follow-up period was 19.9 months (range, 1.2-72.3 months). The median tumor size was 36.5 mm (range, 11-124 mm). Kaplan-Meier estimates of the 2-year overall survival, progression-free survival, and local tumor control rates were 76%, 60%, and 94%, respectively. One patient (2.5%) developed a grade 3 gastric ulcer and one (2.5%) developed grade 3 ascites retention; none of the remaining patients developed grade >3 toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.0.). This study indicates that PBT without fiducial markers achieves good local control without severe treatment-related toxicity of the gastrointestinal tract for HCC located within 2 cm of the gastrointestinal tract.
Collapse
Affiliation(s)
- Miu Mizuhata
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Shigeyuki Takamatsu
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
- Department of Radiotherapy, Kanazawa University Hospital, Kanazawa city, Ishikawa 920-8641, Japan.
| | - Satoshi Shibata
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Sayuri Bou
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Yoshitaka Sato
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Mariko Kawamura
- Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya city, Aichi 466-8560, Japan.
| | - Satoko Asahi
- Department of Radiology, University of Fukui, Fukui City 910-1193, Fukui, Japan.
| | - Yuji Tameshige
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Yoshikazu Maeda
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Makoto Sasaki
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Tomoyasu Kumano
- Department of Radiotherapy, Kanazawa University Hospital, Kanazawa city, Ishikawa 920-8641, Japan.
| | - Satoshi Kobayashi
- Department of Radiology, Kanazawa University, Kanazawa City, Ishikawa 920-8641, Japan.
| | - Kazutaka Yamamoto
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Hiroyasu Tamamura
- Proton Therapy Center, Fukui Prefectural Hospital, Fukui city, Fukui 910-8526, Japan.
| | - Toshifumi Gabata
- Department of Radiology, Kanazawa University, Kanazawa City, Ishikawa 920-8641, Japan.
| |
Collapse
|
|
41
|
Choi SH, Seong J. Strategic application of radiotherapy for hepatocellular carcinoma. Clin Mol Hepatol 2018; 24:114-134. [PMID: 29439305 PMCID: PMC6038936 DOI: 10.3350/cmh.2017.0073] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Accepted: 12/06/2017] [Indexed: 12/22/2022] Open
Abstract
With increasing clinical use, radiotherapy (RT) has been considered reliable and effective method for hepatocellular carcinoma (HCC) treatment, depending on extent of disease and patient characteristics. RT for HCC can improve therapeutic outcomes through excellent local control, downstaging, conversion from unresectable to resectable status, and treatments of unresectable HCCs with vessel invasion or multiple intrahepatic metastases. In addition, further development of modern RT technologies, including image-guided radiotherapy (IGRT), intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy, has expanded the indication of RT. An essential feature of IGRT is that it allows image guidance therapy through in-room images obtained during radiation delivery. Compared with 3D-conformal RT, distinctions of IMRT are inverse treatment planning process and use of a large number of treatment fields or subfields, which provide high precision and exquisitely conformal dose distribution. These modern RT techniques allow more precise treatment by reducing inter- and intra-fractional errors resulting from daily changes and irradiated dose at surrounding normal tissues. More recently, particle therapy has been actively investigated to improve effectiveness of RT. This review discusses modern RT strategies for HCC, as well as optimal selection of RT in multimodal approach for HCC.
Collapse
Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
42
|
Kasuya G, Kato H, Yasuda S, Tsuji H, Yamada S, Haruyama Y, Kobashi G, Ebner DK, Okada NN, Makishima H, Miyazaki M, Kamada T, Tsujii H, for the Liver Cancer Working Group. Progressive hypofractionated carbon-ion radiotherapy for hepatocellular carcinoma: Combined analyses of 2 prospective trials. Cancer 2017; 123:3955-3965. [PMID: 28662297 PMCID: PMC5655922 DOI: 10.1002/cncr.30816] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 04/29/2017] [Accepted: 05/05/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND The objective of this study was to evaluate the safety and efficacy of carbon-ion radiotherapy (CIRT) in patients with hepatocellular carcinoma (HCC) with stepwise dose escalation and hypofractionation in 2 combined prospective trials. METHODS Sequential phase 1/2 (protocol 9603) and phase 2 (protocol 0004) trials were conducted for patients with histologically proven HCC. The phase 1 component of protocol 9603 was a dose-escalation study; CIRT was delivered in 12, 8, or 4 fractions. After determination of the recommended dose, 2 phase 2 trials were performed in an expanded cohort, and the data were pooled to analyze toxicity, local control, and overall survival. RESULTS In the phase 1 component of protocol 9603, 69.6, 58.0, and 52.8 Gy (relative biological effectiveness [RBE]) in 12, 8, and 4 fractions, respectively, constituted the maximum tolerated doses, and 52.8 Gy (RBE) in 4 fractions was established as the recommended dose regimen for the 2 phase 2 studies. In 124 patients with a total of 133 lesions, few severe adverse effects occurred, and local-control and overall survival rates at 1, 3, and 5 years were 94.7% and 90.3%, 91.4% and 50.0%, and 90.0% and 25.0%, respectively; this included 1-, 3-, and 5-year local-control rates of 97.8%, 95.5%, and 91.6%, respectively, in the phase 2 study. In a multivariate analysis, Child-Pugh class B and the presence of a tumor thrombus were significant factors for mortality. CONCLUSIONS The safety and efficacy of CIRT in 12, 8, and 4 fractions were confirmed, with 52.8 Gy (RBE) in 4 fractions established as the recommended treatment course for eligible HCC patients. Cancer 2017;123:3955-65. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Collapse
Affiliation(s)
- Goro Kasuya
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | | | - Shigeo Yasuda
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
- Chiba Rosai HospitalChibaJapan
| | - Hiroshi Tsuji
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | - Shigeru Yamada
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | - Yasuo Haruyama
- Department of Public HealthDokkyo Medical UniversityTochigiJapan
| | - Gen Kobashi
- Department of Public HealthDokkyo Medical UniversityTochigiJapan
| | - Daniel K. Ebner
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
- Brown University Alpert Medical SchoolProvidenceRhode Island
| | - Naomi Nagatake Okada
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | - Hirokazu Makishima
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | - Masaru Miyazaki
- International University of Health and WelfareMita HospitalTokyoJapan
| | - Tadashi Kamada
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | - Hirohiko Tsujii
- Hospital of the National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChibaJapan
| | | |
Collapse
|
|
43
|
Komatsu S, Kido M, Asari S, Toyama H, Ajiki T, Demizu Y, Terashima K, Okimoto T, Sasaki R, Fukumoto T. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: A matched-pair analysis. Surgery 2017; 162:1241-1249. [PMID: 29031927 DOI: 10.1016/j.surg.2017.08.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 08/04/2017] [Accepted: 08/16/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus carries a dismal prognosis, and the feasibility of local treatment has remained controversial. The present study aimed to compare the outcomes of particle radiotherapy and liver resection in patients with hepatocellular carcinoma with inferior vena cava tumor thrombus. METHODS Thirty-one and 19 patients, respectively, underwent particle radiotherapy and liver resection for hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair analysis was undertaken to compare the short- and long-term outcomes according to tumor stage determined using the tumor-node-metastasis classification. RESULTS Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors, including treatment policy and patient and tumor characteristics. The median survival time of matched patients with stage IIIB tumors in the particle radiotherapy group was greater than that in the liver resection group (748 vs 272 days, P = .029), whereas no significant difference was observed in the median survival times of patients with stage IV tumors (239 vs 311 days, respectively). There were significantly fewer treatment-related complications of grade 3 or greater in the particle radiotherapy group (0%) than in the liver resection group (26%). CONCLUSION Particle radiotherapy is potentially preferable in hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor thrombus and at least equal in efficiency to liver resection in those with stage IV disease, while causing significantly fewer complications. Considering the relatively high survival and low invasiveness of particle radiotherapy when compared to liver resection, this approach may represent a novel treatment modality for hepatocellular carcinoma with inferior vena cava tumor thrombus.
Collapse
Affiliation(s)
- Shohei Komatsu
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Sadaki Asari
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Tetsuo Ajiki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yusuke Demizu
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Kazuki Terashima
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Tomoaki Okimoto
- Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo, Japan
| | - Ryohei Sasaki
- Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| |
Collapse
|
|
44
|
A systematic review of publications on charged particle therapy for hepatocellular carcinoma. Int J Clin Oncol 2017; 23:423-433. [PMID: 28871342 DOI: 10.1007/s10147-017-1190-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 08/21/2017] [Indexed: 02/08/2023]
Abstract
Charged particle therapy (proton beam therapy and carbon ion therapy) is a form of radiotherapy which has the unique characteristic of superior depth dose distribution, and has been used for the treatment of hepatocellular carcinoma (HCC) in a limited number of patients, especially in Japan. We undertook a systematic review to define the clinical utility of charged particle therapy for patients with HCC. We searched the MEDLINE database from 1983 to June 2016 to identify clinical studies on charged particle therapy for HCC. Primary outcomes of interest were local control, overall survival, and late radiation morbidities. A total of 13 cohorts from 11 papers were selected from an initial dataset of 78 papers. They included a randomized controlled trial comparing proton beam therapy with transarterial chemoembolization, 9 phase I or II trials and 2 retrospective studies. The reported actuarial local control rates ranged from 71.4-95% at 3 years, and the overall survival rates ranged from 25-42.3% at 5 years. Late severe radiation morbidities were uncommon, and a total of 18 patients with grade ≥3 late adverse events were reported among the 787 patients included in this analysis. Charged particle therapy for HCC was associated with good local control with limited probability of severe morbidities. The cost-effectiveness and the distinctive clinical advantages of charged particle therapies should be clarified in order to become a socially accepted treatment modality for HCC.
Collapse
|
|
45
|
Yeung RH, Chapman TR, Bowen SR, Apisarnthanarax S. Proton beam therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 2017; 17:911-924. [PMID: 28825506 DOI: 10.1080/14737140.2017.1368392] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Radiation therapy is an effective treatment option for hepatocellular carcinoma (HCC) patients. However, radiotherapy for HCC still has limited recognition as a standard treatment option in international consensus guidelines due to a paucity of randomized controlled trials and the risk of hepatotoxicity, which is primarily mediated by baseline liver function and dose delivered to non-tumor liver cells. Proton beam therapy (PBT) may offer advantages over photon-based radiation treatments through its dosimetric characteristic of sparing more liver volume at low to moderate doses. PBT has the potential to reduce radiation-related hepatotoxicity and allow for tumor dose escalation. Areas covered: This article reviews the clinical rationale for using PBT for HCC patients and clinical outcome and toxicity data from retrospective and prospective studies. PBT-specific technical challenges for these tumors and appropriate selection of patients to be treated with PBT are discussed. Expert commentary: Local control, overall survival, and toxicity results are promising for liver PBT. Future studies, including ongoing randomized cooperative group trials, will aim to determine the incremental benefit of PBT over photons and which patients are most suitable for PBT.
Collapse
Affiliation(s)
- Rosanna H Yeung
- a Department of Radiation Oncology , University of Washington , Seattle WA , USA
| | - Tobias R Chapman
- b Department of Radiation Oncology , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston MA , USA
| | - Stephen R Bowen
- a Department of Radiation Oncology , University of Washington , Seattle WA , USA.,c Department of Radiology , University of Washington , Seattle WA , USA
| | | |
Collapse
|
|
46
|
Keane FK, Hong TS. Role and Future Directions of External Beam Radiotherapy for Primary Liver Cancer. Cancer Control 2017; 24:1073274817729242. [PMID: 28975835 PMCID: PMC5937246 DOI: 10.1177/1073274817729242] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 02/28/2017] [Indexed: 12/13/2022] Open
Abstract
The incidence of primary liver cancers continues to increase in the United States and worldwide. The majority of patients with primary liver cancer are not candidates for curative therapies such as surgical resection or orthotopic liver transplantation due to tumor size, vascular invasion, or underlying comorbidities. Therefore, while primary liver cancer is the sixth-most common cancer diagnosis worldwide, it represents the second leading cause of cancer-related deaths. Radiotherapy traditionally played a limited role in the treatment of primary liver cancer due to concerns over hepatic tolerance and the inability to deliver a tumoricidal dose of radiotherapy while still sparing normal hepatic parenchyma. However, the development of modern radiotherapy techniques has made liver-directed radiotherapy a safe and effective treatment option for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. An increasing body of literature has demonstrated the excellent local control and survival rates associated with liver-directed radiotherapy. These data include multiple radiotherapy techniques and modalities, including stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and charged particle therapy, including proton therapy. In this review, we discuss the development of liver-directed radiotherapy and evidence in support of its use, particularly in patients who are not candidates for resection or orthotopic liver transplantation. We also discuss future directions for its role in the management of primary liver cancers.
Collapse
Affiliation(s)
- Florence K. Keane
- Department of Radiation Oncology, Massachusetts General Hospital,
Boston, MA, USA
| | - Theodore S. Hong
- Department of Radiation Oncology, Massachusetts General Hospital,
Boston, MA, USA
| |
Collapse
|
|
47
|
Fukuda K, Okumura T, Abei M, Fukumitsu N, Ishige K, Mizumoto M, Hasegawa N, Numajiri H, Ohnishi K, Ishikawa H, Tsuboi K, Sakurai H, Hyodo I. Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma. Cancer Sci 2017; 108:497-503. [PMID: 28012214 PMCID: PMC5378259 DOI: 10.1111/cas.13145] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 12/07/2016] [Accepted: 12/18/2016] [Indexed: 12/16/2022] Open
Abstract
Long-term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long-term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0-2, Child-Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0-77.0 GyE was administered in 10-35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression-free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5-year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5-year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1-2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long-term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).
Collapse
Affiliation(s)
- Kuniaki Fukuda
- Department of GastroenterologyFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Toshiyuki Okumura
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Masato Abei
- Department of GastroenterologyFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Nobuyoshi Fukumitsu
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Kazunori Ishige
- Department of GastroenterologyFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Masashi Mizumoto
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Naoyuki Hasegawa
- Department of GastroenterologyFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Haruko Numajiri
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Kayoko Ohnishi
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Hitoshi Ishikawa
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Koji Tsuboi
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Hideyuki Sakurai
- Department of Radiation Oncology and Proton Medical Research CenterFaculty of MedicineUniversity of TsukubaIbarakiJapan
| | - Ichinosuke Hyodo
- Department of GastroenterologyFaculty of MedicineUniversity of TsukubaIbarakiJapan
| |
Collapse
|
|
48
|
Abstract
Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer.
Collapse
Affiliation(s)
- Makoto Shinoto
- Ion Beam Therapy Center, SAGA HIMAT Foundation, Saga, Japan
| | - Daniel K Ebner
- Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.,Brown University Alpert Medical School, Providence, RI, USA
| | - Shigeru Yamada
- Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
| |
Collapse
|
|
49
|
Rim CH, Seong J. Application of radiotherapy for hepatocellular carcinoma in current clinical practice guidelines. Radiat Oncol J 2016; 34:160-167. [PMID: 27730805 PMCID: PMC5066447 DOI: 10.3857/roj.2016.01970] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 09/19/2016] [Accepted: 09/20/2016] [Indexed: 12/19/2022] Open
Abstract
In oncologic practice, treatment guidelines provide appropriate treatment strategies based on evidence. Currently, many guidelines are used, including those of the European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL-EORTC), National Comprehensive Cancer Network (NCCN), Asia-Pacific Primary Liver Cancer Expert (APPLE), and Korean Liver Cancer Study Group and National Cancer Centre (KLCSG-NCC). Although radiotherapy is commonly used in clinical practice, some guidelines do not accept it as a standard treatment modality. In this review, we will investigate the clinical practice guidelines currently used, and discuss the application of radiotherapy.
Collapse
Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
50
|
Park SH, Kim JC, Kang MK. Technical advances in external radiotherapy for hepatocellular carcinoma. World J Gastroenterol 2016; 22:7311-7321. [PMID: 27621577 PMCID: PMC4997637 DOI: 10.3748/wjg.v22.i32.7311] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 06/21/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023] Open
Abstract
Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy.
Collapse
|