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Shu J, Zhang J, Jee K, Liu L, Hu M, Huo W, Cui X, Wang H, Lu HM. Impact of iodinated oil in proton therapy on relative stopping power of liver post-cTACE. Phys Med Biol 2024; 69:09NT03. [PMID: 38537311 DOI: 10.1088/1361-6560/ad388b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 03/27/2024] [Indexed: 04/18/2024]
Abstract
Objective. Conventional transarterial chemoembolization (cTACE) is a common treatment for hepatocellular carcinoma (HCC), often with unsatisfactory local controls. Combining cTACE with radiotherapy shows a promise for unresectable large HCC, with proton therapy preserving healthy liver tissue. However, the proton therapy benefits are subject to the accuracy of tissue relative stopping power (RSP) prediction. The RSP values are typically derived from computed tomography (CT) images using stoichiometric calibration. Lipiodol deposition significantly increases CT numbers in liver regions of post-cTACE. Hence, it is necessary to evaluate the accuracy of RSP in liver regions of post-cTACE.Approach. Liver, water, and iodinated oil samples were prepared. Some liver samples contained iodinated oil. The water equivalent path length (WEPL) of sample was measured through the pullbacks of spread-out Bragg peak (SOBP) depth-dose profiles scanned in a water tank with and without sample in the beam path. Measured RSP values were compared to estimated RSP values derived from the CT number based on the stoichiometric calibration method.Main results. The measured RSP of water was 0.991, confirming measurement system calibration. After removing the RSP contribution from container walls, the pure iodinated oil and liver samples had RSP values of 1.12 and 1.06, while the liver samples mixed with varying oil volumes (5 ml, 10 ml, 15 ml) showed RSP values of 1.05, 1.05 and 1.06. Using the stoichiometric calibration method, pure iodinated oil and liver samples had RSP values of 2.79 and 1.06. Liver samples mixed with iodinated oil (5 ml, 10 ml, 15 ml) had calculated RSP values of 1.21, 1.34, and 1.46. The RSP discrepancy reached 149.1% for pure iodinated oil.Significance.Iodinated oil notably raises CT numbers in liver tissue. However, there is almost no effect on its RSP value. Proton treatment of post-cTACE HCC patients can therefore be overshooting if no proper measures are taken against this specific effect.
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Affiliation(s)
- Jiong Shu
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
- University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Jianguang Zhang
- Department of oncology, zibo wanjie hospital, Zibo, Shandong, 255213, People's Republic of China
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, United States of America
| | - Kyungwook Jee
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, United States of America
| | - LingLing Liu
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
- University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Man Hu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People's Republic of China
| | - Wanli Huo
- Key Laboratory of Electromagnetic Wave Information Technology and Metrology of Zhejiang Province, College of Information Engineering, China Jiliang University, Hangzhou, 310018, People's Republic of China
| | - Xiangli Cui
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Hongzhi Wang
- Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
- University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, People's Republic of China
| | - Hsiao-Ming Lu
- Hefei Ion Medical Center, Hefei, Anhui, 230088, People's Republic of China
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Bonù ML, Nicosia L, Turkaj A, Pastorello E, Vitali P, Frassine F, Toraci C, Spiazzi L, Lechiara M, Frittoli B, Grazioli L, Ghirardelli P, Costantino G, Barbera F, Borghetti P, Triggiani L, Portolani N, Buglione M, Dionisi F, Giacomelli I, Lancia A, Magrini SM, Tomasini D. High dose proton and photon-based radiation therapy for 213 liver lesions: a multi-institutional dosimetric comparison with a clinical perspective. LA RADIOLOGIA MEDICA 2024; 129:497-506. [PMID: 38345714 PMCID: PMC10942931 DOI: 10.1007/s11547-024-01788-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 01/15/2024] [Indexed: 03/16/2024]
Abstract
BACKGROUND Stereotactic radiotherapy (SRT) and Proton therapy (PT) are both options in the management of liver lesions. Limited clinical-dosimetric comparison are available. Moreover, dose-constraint routinely used in liver PT and SRT considers only the liver spared, while optimization strategies to limit the liver damaged are poorly reported. METHODS Primary endpoint was to assess and compare liver sparing of four contemporary RT techniques. Secondary endpoints were freedom from local recurrence (FFLR), overall survival (OS), acute and late toxicity. We hypothesize that Focal Liver Reaction (FLR) is determined by a similar biologic dose. FLR was delineated on follow-up MRI. Mean C.I. was computed for all the schedules used. A so-called Fall-off Volume (FOV) was defined as the area of healthy liver (liver-PTV) receiving more than the isotoxic dose. Fall-off Volume Ratio (FOVR) was defined as ratio between FOV and PTV. RESULTS 213 lesions were identified. Mean best fitting isodose (isotoxic doses) for FLR were 18Gy, 21.5 Gy and 28.5 Gy for 3, 5 and 15 fractions. Among photons, an advantage in terms of healthy liver sparing was found for Vmat FFF with 5mm jaws (p = 0.013) and Cyberknife (p = 0.03). FOV and FOVR resulted lower for PT (p < 0.001). Three years FFLR resulted 83%. Classic Radiation induced liver disease (RILD, any grade) affected 2 patients. CONCLUSIONS Cyberknife and V-MAT FFF with 5mm jaws spare more liver than V-MAT FF with 10 mm jaws. PT spare more liver compared to photons. FOV and FOVR allows a quantitative analysis of healthy tissue sparing performance showing also the quality of plan in terms of dose fall-off.
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Affiliation(s)
- Marco Lorenzo Bonù
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy.
| | - Luca Nicosia
- Department of Radiation Oncology, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | | | - Edoardo Pastorello
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Paola Vitali
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Francesco Frassine
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Cristian Toraci
- Department of Medical Physics, Spedali Civili di Brescia, Brescia, Italy
| | - Luigi Spiazzi
- Department of Medical Physics, Spedali Civili di Brescia, Brescia, Italy
| | - Marco Lechiara
- Department of Radiology, Spedali Civili di Brescia, Brescia, Italy
| | - Barbara Frittoli
- Department of Radiology, Spedali Civili di Brescia, Brescia, Italy
| | - Luigi Grazioli
- Department of Radiology, Spedali Civili di Brescia, Brescia, Italy
| | - Paolo Ghirardelli
- Department of Radiation Oncology, Humanitas Gavazzeni Hospital, Bergamo, Italy
| | - Gianluca Costantino
- Department of Radiation Oncology, Humanitas Gavazzeni Hospital, Bergamo, Italy
| | - Fernando Barbera
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Paolo Borghetti
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Luca Triggiani
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | | | - Michela Buglione
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | | | | | - Andrea Lancia
- Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Stefano Maria Magrini
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
| | - Davide Tomasini
- Department of Radiation Oncology, Istituto del Radio O. Alberti, University of Brescia and Spedali Civili Hospital, Piazzale Spedali Civili 1, 25121, Brescia, Italy
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Niitsu H, Mizumoto M, Li Y, Nakamura M, Ishida T, Iizumi T, Saito T, Numajiri H, Makishima H, Nakai K, Oshiro Y, Maruo K, Sakurai H. Tumor Response on Diagnostic Imaging after Proton Beam Therapy for Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:357. [PMID: 38254846 PMCID: PMC10814092 DOI: 10.3390/cancers16020357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. METHODS Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. RESULTS The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6-12 months, and 14.5% at 13-24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. CONCLUSIONS It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.
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Affiliation(s)
- Hikaru Niitsu
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Masashi Mizumoto
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Yinuo Li
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Masatoshi Nakamura
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Toshiki Ishida
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Takashi Iizumi
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Takashi Saito
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Haruko Numajiri
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Hirokazu Makishima
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Kei Nakai
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
| | - Yoshiko Oshiro
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
- Department of Radiation Oncology, Tsukuba Medical Center Hospital, Tsukuba 305-8558, Ibaraki, Japan
| | - Kazushi Maruo
- Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tsukuba 305-8576, Ibaraki, Japan;
| | - Hideyuki Sakurai
- Proton Medical Research Center, Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, Japan; (H.N.); (Y.L.); (M.N.); (T.I.); (T.I.); (T.S.); (H.N.); (H.M.); (K.N.); (Y.O.); (H.S.)
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Lee SU, Kim TH. Current evidence and the potential role of proton beam therapy for hepatocellular carcinoma. Clin Mol Hepatol 2023; 29:958-968. [PMID: 37822213 PMCID: PMC10577334 DOI: 10.3350/cmh.2023.0274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 08/24/2023] [Accepted: 08/27/2023] [Indexed: 10/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and external beam radiation therapy has emerged as a promising approach for managing HCC. Proton beam therapy (PBT) offers dosimetric advantages over X-ray therapy, with superior physical properties known as the Bragg peak. PBT holds promise for reducing hepatotoxicity and allowing safe dose-escalation to the tumor. It has been tried in various clinical conditions and has shown promising local tumor control and survival outcomes. A recent phase III trial demonstrated the non-inferiority of PBT in local tumor control compared to current standard radiofrequency ablation in early-stage HCC. PBT also tended to show more favorable outcomes compared to transarterial chemoembolization in the intermediate stage, and has proven effective in-field disease control and safe toxicity profiles in advanced HCC. In this review, we discuss the rationale, clinical studies, optimal indication, and future directions of PBT in HCC treatment.
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Affiliation(s)
- Sung Uk Lee
- Center for Proton Therapy, National Cancer Center, Goyang, Korea
| | - Tae Hyun Kim
- Center for Proton Therapy, National Cancer Center, Goyang, Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
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Shanbhag NM. A Radiation Oncologist's Journey Through Technological Advancements in Oncology: Reflections on the Proton Therapy Winterschool at Paul Scherrer Institute, Switzerland. Cureus 2023; 15:e39551. [PMID: 37250609 PMCID: PMC10220324 DOI: 10.7759/cureus.39551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 05/31/2023] Open
Abstract
The proton therapy course at the Paul Scherrer Institute (PSI) in Switzerland provided a comprehensive insight into the clinical, physics, and technological aspects of proton therapy, with a particular focus on pencil beam scanning techniques. The program consisted of engaging lectures, hands-on workshops, and facility tours, which covered topics such as the history of proton therapy, treatment planning systems, clinical applications, and future developments. Participants gained practical experience with treatment planning and simulation, while also exploring the challenges associated with various tumor types and motion management. The collaborative and supportive learning environment fostered by the faculty and staff at PSI enriched the educational experience, empowering participants to better serve their patients in the field of radiation oncology.
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Affiliation(s)
- Nandan M Shanbhag
- Oncology/Palliative Care, Tawam Hospital, Al Ain, ARE
- Oncology/Radiation Oncolgy, Tawam Hospital, Al Ain, ARE
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6
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Chami P, Jarnagin W, Abou-Alfa GK, Harding J, Kim N, Lin H, El Homsi M, Crane C, Hajj C. Non-Surgical Locoregional Therapies Alone or in Combination with Systemic Therapy in Patients with Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:1748. [PMID: 36980634 PMCID: PMC10046599 DOI: 10.3390/cancers15061748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/09/2023] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the third-leading cause of cancer-related deaths worldwide. Curative intent treatment options for patients with HCC include liver transplantation, resection and ablation of small lesions. Other potentially curative therapies include cryoablation, microwave ablation and percutaneous alcohol injection. For locally advanced disease, different arterially directed therapies including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation including three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, stereotactic body radiation therapy and proton beam therapy, are available or studied. Systemic therapies based on checkpoint inhibitors and tyrosine kinase inhibitors are available for the management of metastatic HCC and sometimes for locally advanced disease. Combinations of locoregional therapies with systemic drugs are currently the subject of several clinical trials.
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Affiliation(s)
- Perla Chami
- Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut 1107, Lebanon
| | - William Jarnagin
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Surgery, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - James Harding
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY 10021, USA
| | - Neal Kim
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Haibo Lin
- New York Proton Center, New York, NY 10035, USA
| | - Maria El Homsi
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | | | - Carla Hajj
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
- New York Proton Center, New York, NY 10035, USA
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7
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Zaki P, Chuong MD, Schaub SK, Lo SS, Ibrahim M, Apisarnthanarax S. Proton Beam Therapy and Photon-Based Magnetic Resonance Image-Guided Radiation Therapy: The Next Frontiers of Radiation Therapy for Hepatocellular Carcinoma. Technol Cancer Res Treat 2023; 22:15330338231206335. [PMID: 37908130 PMCID: PMC10621304 DOI: 10.1177/15330338231206335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 08/21/2023] [Accepted: 09/21/2023] [Indexed: 11/02/2023] Open
Abstract
External beam radiation therapy (EBRT) has increasingly been utilized in the treatment of hepatocellular carcinoma (HCC) due to technological advances with positive clinical outcomes. Innovations in EBRT include improved image guidance, motion management, treatment planning, and highly conformal techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT). Moreover, proton beam therapy (PBT) and magnetic resonance image-guided radiation therapy (MRgRT) have expanded the capabilities of EBRT. PBT offers the advantage of minimizing low- and moderate-dose radiation to the surrounding normal tissue, thereby preserving uninvolved liver and allowing for dose escalation. MRgRT provides the advantage of improved soft tissue delineation compared to computerized tomography (CT) guidance. Additionally, MRgRT with online adaptive therapy is particularly useful for addressing motion not otherwise managed and reducing high-dose radiation to the normal tissue such as the stomach and bowel. PBT and online adaptive MRgRT are emerging technological advancements in EBRT that may provide a significant clinical benefit for patients with HCC.
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Affiliation(s)
- Peter Zaki
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Michael D. Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, FL, USA
| | - Stephanie K. Schaub
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Simon S. Lo
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Mariam Ibrahim
- School of Medicine, St. George's University, St. George's, Grenada
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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.
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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;
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9
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Apisarnthanarax S, Barry A, Cao M, Czito B, DeMatteo R, Drinane M, Hallemeier CL, Koay EJ, Lasley F, Meyer J, Owen D, Pursley J, Schaub SK, Smith G, Venepalli NK, Zibari G, Cardenes H. External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2022; 12:28-51. [PMID: 34688956 DOI: 10.1016/j.prro.2021.09.004] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/07/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). METHODS The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. This guideline is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, as consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or before surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies. CONCLUSIONS The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.
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Affiliation(s)
| | - Aisling Barry
- Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Ontario, Canada
| | - Minsong Cao
- Department of Radiation Oncology, University of California, Los Angeles, California
| | - Brian Czito
- Department of Radiation Oncology, Duke University, Durham, North Carolina
| | - Ronald DeMatteo
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Mary Drinane
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | | | - Eugene J Koay
- Department of Radiation Oncology, UT-MD Anderson Cancer Center, Houston, Texas
| | - Foster Lasley
- Department of Radiation Oncology, GenesisCare, Rogers, Arkansas
| | - Jeffrey Meyer
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland
| | - Dawn Owen
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Jennifer Pursley
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Stephanie K Schaub
- Department of Radiation Oncology, University of Washington, Seattle, Washington
| | - Grace Smith
- Department of Radiation Oncology, UT-MD Anderson Cancer Center, Houston, Texas
| | - Neeta K Venepalli
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
| | - Gazi Zibari
- Department of Transplantation Services, Willis-Knighton Medical Center, Shreveport, Louisiana
| | - Higinia Cardenes
- Department of Radiation Oncology, Weill Cornell, New York, New York
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10
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Duda DG, Hauth FD. Use of Radiotherapy Alone and in Combination with Other Therapies for Hepatocellular Carcinoma: Rationale and Future Directions. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:153-164. [DOI: 10.1007/978-981-19-0063-1_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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11
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Kim TH, Lee KS, Sim SH, Kim YJ, Kim DY, Chae H, Lee EG, Han JH, Jung SY, Lee S, Kang HS, Lee ES. Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer. Front Oncol 2021; 11:783327. [PMID: 34804986 PMCID: PMC8595332 DOI: 10.3389/fonc.2021.783327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 10/20/2021] [Indexed: 11/13/2022] Open
Abstract
Background Few studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC. Material and Methods Seventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60-80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed. Results The median follow-up time was 34.2 months (range, 11.5-56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9-105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3-10.5) and 39.3 months (95% CI, 33.2-51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8-41.0) and 71.7% (95% CI, 46.8-96.6), respectively. Grade 3 or higher adverse events were not observed. Conclusion PBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.
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Affiliation(s)
- Tae Hyun Kim
- Center for Proton Therapy, National Cancer Center, Goyang, South Korea
| | - Keun Seok Lee
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Sung Hoon Sim
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Yeon-Joo Kim
- Center for Proton Therapy, National Cancer Center, Goyang, South Korea
| | - Dae Yong Kim
- Center for Proton Therapy, National Cancer Center, Goyang, South Korea
| | - Heejung Chae
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Eun-Gyeong Lee
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Jai Hong Han
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - So Youn Jung
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Seeyoun Lee
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Han Sung Kang
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
| | - Eun Sook Lee
- Center for Breast Cancer, National Cancer Center, Goyang, South Korea
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12
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Fracchiolla F, Dionisi F, Righetto R, Widesott L, Giacomelli I, Cartechini G, Farace P, Bertolini M, Amichetti M, Schwarz M. Clinical implementation of pencil beam scanning proton therapy for liver cancer with forced deep expiration breath hold. Radiother Oncol 2020; 154:137-144. [PMID: 32976870 DOI: 10.1016/j.radonc.2020.09.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 01/04/2023]
Abstract
PURPOSE To present our technique for liver cancer treatments with proton therapy in pencil beam scanning mode and to evaluate the impact of uncertainties on plan quality. MATERIALS AND METHODS Seventeen patients affected by liver cancer were included in this study. Patients were imaged and treated in forced breath-hold using the Active Breathing Coordinator system and monitored with an optical tracking system. Three simulation CTs were acquired to estimate the anatomical variability between breath-holds and generate an internal target volume (ITV). The treatment plans were optimized with a Single Field Optimization technique aimed at minimizing the use of range shifter. Plan robustness was tested simulating systematic range and setup uncertainties, as well as the interplay effect between breath-holds. The appropriateness of margin was further verified based on the actual positioning data acquired during treatment. RESULTS The dose distributions of the nominal plans achieved a satisfactory target coverage in 11 out of 17 patients, while in the remaining 6 D95 to the PTV was affected by the constraint on mean liver dose. The constraints for all other organs at risk were always within tolerances. The interplay effect had a limited impact on the dose distributions: the worst case scenario showed a D95 reduction in the ITV < 3.9 GyRBE and no OAR with D1 > 105% of the prescription dose. The robustness analysis showed that for 13 out of 17 patients the ITV coverage in terms of D95 was better than D95 of the PTV in the nominal plan. For the remaining 4 patients, the maximum difference between ITV D95 and PTV D95 was ≤0.7% even for the largest simulated setup error and it was deemed clinically acceptable. Hot spots in the OARs were always lower than 105% of the prescription dose. Positioning images confirmed that the breath hold technique and the PTV margin were adequate to compensate for inter- and intra-breath-hold variations in liver position. CONCLUSION We designed and clinically applied a technique for the treatment of liver cancer with proton pencil beam scanning in forced deep expiration breath-hold. The initial data on plan robustness and patient positioning suggest that the choices in terms of planning technique and treatment margins are able to reach the desired balance between target coverage and organ at risk sparing.
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Affiliation(s)
- Francesco Fracchiolla
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy.
| | - Francesco Dionisi
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Roberto Righetto
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Lamberto Widesott
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Irene Giacomelli
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | | | - Paolo Farace
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Mattia Bertolini
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Maurizio Amichetti
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy
| | - Marco Schwarz
- Azienda Provinciale per i Servizi Sanitari (APSS) Protontherapy Department, Trento, Italy; TIFPA Trento Institute for Fundamental Physics and Applications, Italy
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13
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Kim TH, Park JW, Kim BH, Oh ES, Youn SH, Moon SH, Kim SS, Woo SM, Koh YH, Lee WJ, Kim DY. Phase II Study of Hypofractionated Proton Beam Therapy for Hepatocellular Carcinoma. Front Oncol 2020; 10:542. [PMID: 32411594 PMCID: PMC7198869 DOI: 10.3389/fonc.2020.00542] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 03/26/2020] [Indexed: 12/16/2022] Open
Abstract
Background: Proton beam has an excellent depth dose distribution due to its unique physical properties, and thus proton beam therapy (PBT) has been tried and showed promising outcomes in hepatocellular carcinoma (HCC). The purpose of this phase II study is to evaluate the efficacy of hypofractionated PBT in HCC. Methods: The eligibility criteria for this study were as follows: patients with HCC lesion(s) who were failed after, were difficult to treat with, or refused to other local treatments; tumor size and number of ≤7 and ≤2 cm, respectively, and HCC lesion(s) of ≥2 cm from gastrointestinal organs; Child–Pugh score of ≤7; Eastern Cooperative Oncology Group performance status ≤1; and age ≥18 years. The prescribed dose of PBT was 70 Gy equivalent in 10 fractions. The primary endpoint was 3-year local progression-free survival (LPFS) rate. Results: Forty-five patients were prospectively enrolled, and there were 35 men and 10 women with a median age of 63 years (range, 46–78 years). Thirty-seven patients had recurrent and/or residual disease, and eight patients had treatment-naive disease. All patients received the planned treatments without treatment interruption, and grade ≥3 acute toxicity did not occur. The median follow-up duration was 35.1 months (range, 11.2–56.3 months) and local progression occurred in two patients (8.7%). The 3-year rates of LPFS and overall survival (OS) were 95.2% (95% confidence interval [CI], 89.1%−100%) and 86.4% (95% CI, 72.9–99.9%), respectively. Conclusion: Hypofractionated PBT showed promising LPFS and OS, and further studies are warranted to compare PBT with other local modalities.
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Affiliation(s)
- Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.,Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Eun Sang Oh
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Sang Hee Youn
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Sung Ho Moon
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Sang Soo Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Young-Hwan Koh
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
| | - Dae Yong Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, South Korea
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14
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Cerrito L, Annicchiarico BE, Iezzi R, Gasbarrini A, Pompili M, Ponziani FR. Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers. World J Gastroenterol 2019; 25:4360-4382. [PMID: 31496618 PMCID: PMC6710186 DOI: 10.3748/wjg.v25.i31.4360] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 06/24/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
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MESH Headings
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Hepatocellular/complications
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Contrast Media/administration & dosage
- Disease-Free Survival
- Hepatectomy
- Humans
- Hypertension, Portal/etiology
- Hypertension, Portal/mortality
- Hypertension, Portal/therapy
- Liver Neoplasms/complications
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Liver Transplantation
- Neoadjuvant Therapy/methods
- Neoplasm Invasiveness/pathology
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/prevention & control
- Patient Selection
- Portal Vein/diagnostic imaging
- Portal Vein/pathology
- Prognosis
- Survival Analysis
- Thrombectomy
- Time Factors
- Ultrasonography/methods
- Venous Thrombosis/etiology
- Venous Thrombosis/mortality
- Venous Thrombosis/therapy
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Affiliation(s)
- Lucia Cerrito
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Brigida Eleonora Annicchiarico
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maurizio Pompili
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Division of Internal Medicine, Gastroenterology and Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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15
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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.
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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
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16
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Kim TH, Park JW, Kim BH, Kim H, Moon SH, Kim SS, Woo SM, Koh YH, Lee WJ, Kim DY, Kim CM. Does Risk-Adapted Proton Beam Therapy Have a Role as a Complementary or Alternative Therapeutic Option for Hepatocellular Carcinoma? Cancers (Basel) 2019; 11:cancers11020230. [PMID: 30781391 PMCID: PMC6406298 DOI: 10.3390/cancers11020230] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Revised: 01/30/2019] [Accepted: 02/12/2019] [Indexed: 02/08/2023] Open
Abstract
To evaluate the role of risk-adapted proton beam therapy (PBT) in hepatocellular carcinoma (HCC) patients, a total of 243 HCC patients receiving risk-adapted PBT with three dose-fractionation regimens (regimen A [n = 40], B [n = 60], and C [n = 143]) according to the proximity of their gastrointestinal organs (<1 cm, 1–1.9 cm, and ≥2 cm, respectively) were reviewed: The prescribed doses to planning target volume 1 (PTV1) were 50 gray equivalents (GyE) (EQD2 [equivalent dose in 2 Gy fractions], 62.5 GyE10), 60 GyE (EQD2, 80 GyE10), and 66 GyE (EQD2, 91.3 GyE10) in 10 fractions, respectively, and those of PTV2 were 30 GyE (EQD2, 32.5 GyE10) in 10 fractions. In all patients, the five-year local recurrence-free survival (LRFS) and overall survival (OS) rates were 87.5% and 48.1%, respectively, with grade ≥3 toxicity of 0.4%. In regimens A, B, and C, the five-year LRFS and OS rates were 54.6%, 94.7%, and 92.4% (p < 0.001), and 16.7%, 39.2%, and 67.9% (p < 0.001), respectively. The five-year OS rates of the patients with the Modified Union for International Cancer Control (mUICC) stages I, II, III, and IVA and Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C were 69.2%, 65.4%, 43.8%, and 26.6% (p < 0.001), respectively, and 65.1%, 40%, and 32.2% (p < 0.001), respectively. PBT could achieve promising long-term tumor control and have a potential role as a complementary or alternative therapeutic option across all stages of HCC.
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Affiliation(s)
- Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Hyunjung Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Sung Ho Moon
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Sang Soo Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Young-Hwan Koh
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Dae Yong Kim
- Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea.
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17
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Schaub SK, Hartvigson PE, Lock MI, Høyer M, Brunner TB, Cardenes HR, Dawson LA, Kim EY, Mayr NA, Lo SS, Apisarnthanarax S. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Current Trends and Controversies. Technol Cancer Res Treat 2018; 17:1533033818790217. [PMID: 30068240 PMCID: PMC6071169 DOI: 10.1177/1533033818790217] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide.
Depending on the extent of disease and competing comorbidities for mortality, multiple
liver-directed therapy options exist for the treatment of hepatocellular carcinoma.
Advancements in radiation oncology have led to the emergence of stereotactic body
radiation therapy as a promising liver-directed therapy, which delivers high doses of
radiation with a steep dose gradient to maximize local tumor control and minimize
radiation-induced treatment toxicity. In this study, we review the current clinical data
as well as the unresolved issues and controversies regarding stereotactic body radiation
therapy for hepatocellular carcinoma: (1) Is there a radiation dose–response relationship
with hepatocellular carcinoma? (2) What are the optimal dosimetric predictors of
radiation-induced liver disease, and do they differ for patients with varying liver
function? (3) How do we assess treatment response on imaging? (4) How does stereotactic
body radiation therapy compare to other liver-directed therapy modalities, including
proton beam therapy? Based on the current literature discussed, this review highlights
future possible research and clinical directions.
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Affiliation(s)
- Stephanie K Schaub
- 1 Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Pehr E Hartvigson
- 1 Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Michael I Lock
- 2 Department of Radiation Oncology, University of Western Ontario, London, Canada
| | - Morten Høyer
- 3 Aarhus University Hospital, Danish Center for Particle Therapy, Aarhus, Denmark
| | - Thomas B Brunner
- 4 Klinik für Strahlentherapie, Universitätsklinikum Magdeburg, Magdeburg, Germany
| | | | - Laura A Dawson
- 6 Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
| | - Edward Y Kim
- 1 Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Nina A Mayr
- 1 Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Simon S Lo
- 1 Department of Radiation Oncology, University of Washington, Seattle, WA, USA
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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.
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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
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Kim TH, Park JW, Kim BH, Kim DY, Moon SH, Kim SS, Lee JH, Woo SM, Koh YH, Lee WJ, Kim CM. Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma. Oncotarget 2017; 9:4034-4043. [PMID: 29423102 PMCID: PMC5790519 DOI: 10.18632/oncotarget.23428] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2017] [Accepted: 11/26/2017] [Indexed: 12/17/2022] Open
Abstract
Objective To evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC). Results Overall, treatment was well tolerated with no grade toxicity ≥3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The three-year local progression-free survival (LPFS), relapse-free survival (RFS) and OS rates were 89.9%, 26.8%, and 74.4%, respectively. Multivariate analysis revealed that the tumour response was an independent prognostic factor for LPFS, RFS, and OS. Conclusion Most CR was achieved within 1 year after PBT and further salvage treatments in PBT field might be postponed up to approximately 18–24 months. Hypofractionated PBT could be good alternative for HCC patients who are unsuitable for surgical or invasive treatments with curative intent. Materials and Methods Seventy-one inoperable or recurrent HCC patients underwent hypofractionated PBT using 66 GyE in 10 fractions. The tumour responses were defined as the maximal tumour response observed during the follow-up period using the modified Response Evaluation Criteria in Solid Tumors criteria.
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Affiliation(s)
- Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Dae Yong Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sung Ho Moon
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sang Soo Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Ju Hee Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Young-Hwan Koh
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
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20
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Nielsen S, Bassler N, Grzanka L, Swakon J, Olko P, Andreassen CN, Overgaard J, Alsner J, Sørensen BS. Differential gene expression in primary fibroblasts induced by proton and cobalt-60 beam irradiation. Acta Oncol 2017; 56:1406-1412. [PMID: 28885067 DOI: 10.1080/0284186x.2017.1351623] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Proton beam therapy delivers a more conformal dose distribution than conventional radiotherapy, thus improving normal tissue sparring. Increasing linear energy transfer (LET) along the proton track increases the relative biological effectiveness (RBE) near the distal edge of the Spread-out Bragg peak (SOBP). The severity of normal tissue side effects following photon beam radiotherapy vary considerably between patients. AIM The dual study aim was to identify gene expression patterns specific to radiation type and proton beam position, and to assess whether individual radiation sensitivity influences gene expression levels in fibroblast cultures irradiated in vitro. METHODS The study includes 30 primary fibroblast cell cultures from patients previously classified as either radiosensitive or radioresistant. Cells were irradiated at three different positions in the proton beam profile: entrance, mid-SOBP and at the SOBP distal edge. Dose was delivered in three fractions × 3.5 Gy(RBE) (RBE 1.1). Cobalt-60 (Co-60) irradiation was used as reference. Real-time qPCR was performed to determine gene expression levels for 17 genes associated with inflammation response, fibrosis and angiogenesis. RESULTS Differences in median gene expression levels were observed for multiple genes such as IL6, IL8 and CXCL12. Median IL6 expression was 30%, 24% and 47% lower in entrance, mid-SOBP and SOBP distal edge groups than in Co-60 irradiated cells. No genes were found to be oppositely regulated by different radiation qualities. Radiosensitive patient samples had the strongest regulation of gene expression; irrespective of radiation type. CONCLUSIONS Our findings indicate that the increased LET at the SOBP distal edge position did not generally lead to increased transcriptive response in primary fibroblast cultures. Inflammatory factors were generally less extensively upregulated by proton irradiation compared with Co-60 photon irradiation. These effects may possibly influence the development of normal tissue damage in patients treated with proton beam therapy.
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Affiliation(s)
- Steffen Nielsen
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Niels Bassler
- Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, Sweden
| | - Leszek Grzanka
- Proton Radiotherapy Group, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Jan Swakon
- Proton Radiotherapy Group, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Pawel Olko
- Proton Radiotherapy Group, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | | | - Jens Overgaard
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Jan Alsner
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Brita Singers Sørensen
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
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21
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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.
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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
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22
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Mondlane G, Gubanski M, Lind PA, Henry T, Ureba A, Siegbahn A. Dosimetric Comparison of Plans for Photon- or Proton-Beam Based Radiosurgery of Liver Metastases. Int J Part Ther 2016; 3:277-284. [PMID: 31772978 DOI: 10.14338/ijpt-16-00010.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 07/06/2016] [Indexed: 12/12/2022] Open
Abstract
Purpose Radiosurgery treatment of liver metastases with photon beams has been an established method for more than a decade. One method commonly used is the stereotactic body radiation therapy (SBRT) technique. The aim of this study was to investigate the potential sparing of the organs at risk (OARs) that the use of intensity-modulated proton therapy (IMPT), instead of SBRT, could enable. Patients and Methods A comparative treatment-planning study of photon-beam and proton-beam based liver-cancer radiosurgery was performed. Ten patients diagnosed with liver metastasis and previously treated with SBRT at the Karolinska University Hospital were included in the study. New IMPT plans were prepared for all patients, while the original plans were set as reference plans. The IMPT planning was performed with the objective of achieving the same target dose coverage as with the SBRT plans. Pairwise dosimetric comparisons of the treatment plans were then performed for the OARs. A 2-sided Wilcoxon signed-rank test with significance level of 5% was carried out. Results Improved sparing of the OARs was made possible with the IMPT plans. There was a significant decrease of the mean doses delivered to the following risk organs: the nontargeted part of the liver (P = .002), the esophagus (P = .002), the right kidney (P = .008), the spinal cord (P = .004), and the lungs (P = .002). The volume of the liver receiving less than 15 Gy was significantly increased with the IMPT plans (P = .004). Conclusion The IMPT-based radiosurgery plans provided similar target coverage and significant dose reductions for the OARs compared with the photon-beam based SBRT plans. Further studies including detailed information about varying tissue heterogeneities in the beam path, due to organ motion, are required to evaluate more accurately whether IMPT is preferable for the radiosurgical treatment of liver metastases.
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Affiliation(s)
- Gracinda Mondlane
- Department of Physics - Medical Radiation Physics, Stockholm University, Stockholm, Sweden.,Department of Physics, Universidade Eduardo Mondlane, Maputo, Mozambique
| | - Michael Gubanski
- Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden
| | - Pehr A Lind
- Department of Oncology and Pathology, Karolinska University Hospital, Stockholm, Sweden.,Centre for Clinical Research Sörmland, Uppsala University, Sweden
| | - Thomas Henry
- Department of Physics - Medical Radiation Physics, Stockholm University, Stockholm, Sweden
| | - Ana Ureba
- Department of Physics - Medical Radiation Physics, Stockholm University, Stockholm, Sweden
| | - Albert Siegbahn
- Department of Physics - Medical Radiation Physics, Stockholm University, Stockholm, Sweden
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23
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Kim DY, Park JW, Kim TH, Kim BH, Moon SH, Kim SS, Woo SM, Koh YH, Lee WJ, Kim CM. Risk-adapted simultaneous integrated boost-proton beam therapy (SIB-PBT) for advanced hepatocellular carcinoma with tumour vascular thrombosis. Radiother Oncol 2016; 122:122-129. [PMID: 28034460 DOI: 10.1016/j.radonc.2016.12.014] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 10/09/2016] [Accepted: 12/08/2016] [Indexed: 01/11/2023]
Abstract
PURPOSE To evaluate clinical effectiveness and safety of simultaneous integrated boost-proton beam therapy (SIB-PBT) in hepatocellular carcinoma (HCC) patients with tumour vascular thrombosis (TVT). MATERIAL AND METHODS Forty-one HCC patients with TVT underwent SIB-PBT using three dose-fractionation schemes: if gross tumour volume <1cm (n=27), 1-1.9cm (n=7), and ⩾2cm (n=7) from gastrointestinal structures, 50GyE (EQD2, 62.5GyE10), 60Gy (EQD2, 80GyE10), 66Gy (EQD2, 91.3GyE10), respectively, in 10 fractions was prescribed to planning target volume 1 (PTV1), and 30GyE (EQD2, 32.5GyE10) in 10 fractions was prescribed to PTV2. RESULTS Overall, treatment was well tolerated, with no grade toxicity ⩾3. Median overall survival (OS) was 34.4months and 2-year local progression-free survival (LPFS), relapse free survival (RFS), and OS rates were 88.1%, 25%, and 51.1%, respectively. Patients treated with EQD2 of ⩾80GyE10 tended to show better TVT response (92.8% vs. 55.5%, p=0.002) 2-year LPFS (92.9% vs. 82.5%, p=0.463), RFS (28.8% vs. 19%, p=0.545), and OS (58.4% vs. 46.8%, p=0.428) rates than those with EQD2 of <80GyE10. Multivariate analysis showed that TVT response and Child Pugh classification were independent prognostic factors for OS. CONCLUSIONS SIB-PBT is feasible and promising for HCC patients with TVT.
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Affiliation(s)
- Dae Yong Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Joong-Won Park
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
| | - Bo Hyun Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Sung Ho Moon
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Sang Soo Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Sang Myung Woo
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Young-Hwan Koh
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Woo Jin Lee
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
| | - Chang-Min Kim
- Center for Liver Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
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