|
1
|
Chok KSH, Joeng TYT, Poon DMC. Proton beam therapy in the management of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2025; 19:495-504. [PMID: 40272863 DOI: 10.1080/17474124.2025.2495080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 04/15/2025] [Indexed: 04/26/2025]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Photon radiotherapy shows efficacy in treating HCC but carries risks of high exit dose and radiation-induced liver disease. Additionally, HCCs with portal vein tumor thrombosis (PVTT) have a poor prognosis and are associated with higher risk of death. In recent years, proton beam therapy (PBT) has emerged as a novel treatment with the ability to downstage HCC for liver transplant (LT). AREAS COVERED This review will provide an overview of dosimetric benefits of PBT, efficacy of PBT in treating HCC, downstaging HCC-PVTT for LT, and a comparison of PBT with other non-surgical techniques. A search of PubMed until 3 September 2024 was conducted using free search and the following keywords: hepatocellular carcinoma, proton beam therapy, portal vein tumor thrombosis, local ablative therapy, trans-arterial chemoembolization, stereotactic body radiotherapy, Y-90 radioembolization. EXPERT OPINION Various clinical trials using PBT have shown promising tumor local control and overall survival rates. PBT is mostly safe and efficacious for downstaging HCC-PVTT for LT. PBT has also been shown to be non-inferior to various other treatment modalities. Future research should focus on combinations of PBT with other modalities.
Collapse
Affiliation(s)
- Kenneth S H Chok
- Department of Surgery, The Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Tiffany Y T Joeng
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Darren M C Poon
- Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong, China
| |
Collapse
|
|
2
|
Yamano A, Inoue T, Shiba S, Shimo T, Yamanaka M, Shirata R, Matsumoto K, Yagihashi T, Tokuuye K, Chang W. Dosimetric Evaluation of Beam-specific PTV and Worst-case Optimization Methods for Liver Proton Therapy. In Vivo 2024; 38:3059-3067. [PMID: 39477417 PMCID: PMC11535939 DOI: 10.21873/invivo.13790] [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: 08/05/2024] [Revised: 09/02/2024] [Accepted: 09/12/2024] [Indexed: 11/07/2024]
Abstract
BACKGROUND/AIM In spot-scanning proton therapy, intra-fractional anatomical changes by organ movement can lead to deterioration in dose distribution due to beam range variation. To explore a more robust treatment planning method, this study evaluated the dosimetric characteristics and robustness of two proton therapy planning methods for liver cancer. PATIENTS AND METHODS Two- or three-field treatment plans were created for 11 patients with hepatocellular carcinoma or metastatic liver cancer using a single-field uniform dose (SFUD) technique. The plans were optimized using either beam-specific planning target volume (BSPTV) or worst-case optimization (WCO). The target coverage for the gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OAR) parameters related to toxicity were calculated from the perturbed dose distributions, considering setup and range uncertainties. Statistical analyses of the BSPTV and WCO plans were performed using the Wilcoxon signed-rank sum test (p<0.05). The calculation times for a single optimization process were also recorded and compared. RESULTS The robustness of the WCO plans in the worst-case scenario was significantly higher than that of the BSPTV plan in terms of GTV target coverage, prevention of maximum dose increase to the gastrointestinal tract, and the dose received by normal liver regions. However, there were no significant differences in PTV, and the calculation time required to create the WCO plan was considerably longer. CONCLUSION In SFUD proton therapy for liver cancer, the WCO plans required a longer optimization time but exhibited superior robustness in GTV coverage and sparing of OARs.
Collapse
Affiliation(s)
- Akihiro Yamano
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
- Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan
| | - Tatsuya Inoue
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan;
- Department of Radiation Oncology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Shintaro Shiba
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Takahiro Shimo
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Masashi Yamanaka
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Ryosuke Shirata
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Kazuki Matsumoto
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Takayuki Yagihashi
- Department of Medical Physics, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Koichi Tokuuye
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Weishan Chang
- Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan
| |
Collapse
|
|
3
|
Salem PP, Chami P, Daou R, Hajj J, Lin H, Chhabra AM, Simone CB, Lee NY, Hajj C. Proton Radiation Therapy: A Systematic Review of Treatment-Related Side Effects and Toxicities. Int J Mol Sci 2024; 25:10969. [PMID: 39456752 PMCID: PMC11506991 DOI: 10.3390/ijms252010969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle's biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered.
Collapse
Affiliation(s)
- Peter P. Salem
- Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon; (P.P.S.); (P.C.)
| | - Perla Chami
- Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon; (P.P.S.); (P.C.)
| | - Remy Daou
- Family Medicine Department, Hotel Dieu de France Hospital, Beirut 1660, Lebanon;
| | - Joseph Hajj
- Faculty of Medicine, University of Balamand, Beirut 1100, Lebanon;
| | - Haibo Lin
- New York Proton Center, New York, NY 10035, USA; (H.L.); (A.M.C.); (C.B.S.II); (N.Y.L.)
| | - Arpit M. Chhabra
- New York Proton Center, New York, NY 10035, USA; (H.L.); (A.M.C.); (C.B.S.II); (N.Y.L.)
| | - Charles B. Simone
- New York Proton Center, New York, NY 10035, USA; (H.L.); (A.M.C.); (C.B.S.II); (N.Y.L.)
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Nancy Y. Lee
- New York Proton Center, New York, NY 10035, USA; (H.L.); (A.M.C.); (C.B.S.II); (N.Y.L.)
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| | - Carla Hajj
- New York Proton Center, New York, NY 10035, USA; (H.L.); (A.M.C.); (C.B.S.II); (N.Y.L.)
- Memorial Sloan Kettering Cancer Center, New York, NY 10027, USA
| |
Collapse
|
|
4
|
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.
Collapse
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
| |
Collapse
|
|
5
|
Liou Y, Lan TL, Lan CC. A Meta-Analysis and Review of Radiation Dose Escalation in Definitive Radiation Therapy between Squamous Cell Carcinoma and Adenocarcinoma of Esophageal Cancer. Cancers (Basel) 2024; 16:658. [PMID: 38339409 PMCID: PMC10854668 DOI: 10.3390/cancers16030658] [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: 01/15/2024] [Revised: 01/30/2024] [Accepted: 02/02/2024] [Indexed: 02/12/2024] Open
Abstract
Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management.
Collapse
Affiliation(s)
- Yu Liou
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Beitou District, Taipei City 112, Taiwan
| | - Tien-Li Lan
- Department of Heavy Particles and Radiation Oncology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City 112, Taiwan
| | - Chin-Chun Lan
- Thoracic Surgery Group, Clinical Research Center, Department of Surgery, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua City 500, Taiwan
- Department of Emergency and Critical Care Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua City 500, Taiwan
- Post-Baccalaureate Medical School, National Chung Hsing University, 145 Xingda Rd., South District, Taichung City 402, Taiwan
| |
Collapse
|
|
6
|
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.
Collapse
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.)
| |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Chuang YC, Wu PH, Shen YA, Kuo CC, Wang WJ, Chen YC, Lee HL, Chiou JF. Recent Advances in Metal-Based NanoEnhancers for Particle Therapy. NANOMATERIALS (BASEL, SWITZERLAND) 2023; 13:1011. [PMID: 36985905 PMCID: PMC10056155 DOI: 10.3390/nano13061011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/02/2023] [Accepted: 03/07/2023] [Indexed: 06/18/2023]
Abstract
Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine.
Collapse
Affiliation(s)
- Yao-Chen Chuang
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
| | - Ping-Hsiu Wu
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Proton Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
| | - Yao-An Shen
- Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
| | - Chia-Chun Kuo
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
- Proton Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
- School of Health Care Administration, College of Management, Taipei Medical University, Taipei 110301, Taiwan
- Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Wei-Jun Wang
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
- Proton Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
| | - Yu-Chen Chen
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
| | - Hsin-Lun Lee
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Proton Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
| | - Jeng-Fong Chiou
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 110301, Taiwan; (Y.-C.C.)
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan
- Proton Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan
| |
Collapse
|
|
9
|
Uchinami Y, Katoh N, Abo D, Morita R, Taguchi H, Fujita Y, Kanehira T, Suzuki R, Miyamoto N, Takao S, Matsuura T, Sho T, Ogawa K, Orimo T, Kakisaka T, Kobashi K, Aoyama H. Study of hepatic toxicity in small liver tumors after photon or proton therapy based on factors predicting the benefits of proton. Br J Radiol 2023; 96:20220720. [PMID: 36633335 PMCID: PMC10078862 DOI: 10.1259/bjr.20220720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 11/29/2022] [Accepted: 12/12/2022] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVES In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCCs) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (1 vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity. METHODS We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment. RESULTS In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median: 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors. CONCLUSION The predictive factor numbers predicted the ALBI score change in PBT but not in XRT. ADVANCES IN KNOWLEDGE This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.
Collapse
Affiliation(s)
- Yusuke Uchinami
- Department of Radiation Oncology, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Norio Katoh
- Department of Radiation Oncology, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Daisuke Abo
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Hokkaido, Japan
| | - Ryo Morita
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Hokkaido, Japan
| | - Hiroshi Taguchi
- Department of Radiation Oncology, Hokkaido University Hospital, Hokkaido, Japan
| | - Yoshihiro Fujita
- Department of Radiation Oncology, Hokkaido University Hospital, Hokkaido, Japan
| | - Takahiro Kanehira
- Department of Medical Physics, Hokkaido University Hospital, Hokkaido, Japan
| | - Ryusuke Suzuki
- Department of Medical Physics, Hokkaido University Hospital, Hokkaido, Japan
| | - Naoki Miyamoto
- Department of Medical Physics, Hokkaido University Hospital, Hokkaido, Japan
| | - Seishin Takao
- Department of Radiation Medical Science and Engineering, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Taeko Matsuura
- Department of Radiation Medical Science and Engineering, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Keiji Kobashi
- Global Center for Biomedical Science and Engineering, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| | - Hidefumi Aoyama
- Department of Radiation Oncology, Hokkaido University Faculty of Medicine, Hokkaido, Japan
| |
Collapse
|
|
10
|
Roberts HJ, Hong TS. Proton versus photon radiotherapy for hepatocellular carcinoma: Current data and technical considerations. JOURNAL OF RADIOSURGERY AND SBRT 2023; 9:9-16. [PMID: 38029005 PMCID: PMC10681146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 07/15/2023] [Indexed: 12/01/2023]
Abstract
Radiation is an accepted standard of care for unresectable hepatocellular carcinoma (HCC), and while photon radiation is the current standard, the use of proton beam radiotherapy (PBT) is an active area of investigation given its ability to better spare uninvolved liver. Patients with HCC typically have background liver disease and many patients die of their underlying liver function in the absence of tumor progression. Early photon-based series showed promising rates of local control however the risk of non-classic radiation induced liver disease (RILD) remains relatively high and may be associated with poorer outcomes. There is a theoretical advantage to PBT in its ability to spare uninvolved liver parenchyma and potentially allow for further dose escalation. There are technical considerations for image guidance, respiratory motion management, and conformality to both PBT and photon radiotherapy that are critical to optimizing each modality. Whether the use of PBT affects clinical outcomes is the subject of the ongoing NRG Oncology GI003 trial, that randomizes patients with HCC to protons or photons. This article reviews the technical differences and literature on individual outcomes for PBT and photon radiation as well as the available comparative data.
Collapse
Affiliation(s)
- Hannah J Roberts
- Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA
| |
Collapse
|
|
11
|
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.
Collapse
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
| | | |
Collapse
|
|
12
|
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
|
|
13
|
Uchinami Y, Katoh N, Suzuki R, Kanehira T, Tamura M, Takao S, Matsuura T, Miyamoto N, Fujita Y, Koizumi F, Taguchi H, Yasuda K, Nishioka K, Yokota I, Kobashi K, Aoyama H. A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity. Clin Transl Radiat Oncol 2022; 35:70-75. [PMID: 35633653 PMCID: PMC9130086 DOI: 10.1016/j.ctro.2022.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 05/02/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022] Open
Abstract
An advantage of PBT is reducing the liver receiving low doses of radiation. The factors predicting the benefit in PBT are different among NTCP models. The tumor size, number, and location are useful in estimating the benefits of PBT. Background Materials and methods Results Conclusions
Collapse
|
|
14
|
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
|
|
15
|
Su CW, Hou MM, Huang PW, Chou YC, Huang BS, Tseng JH, Hsu CW, Chang TC, Lin SM, Lin CC. Proton beam radiotherapy combined with anti-PD1/PDL1 immune checkpoint inhibitors for advanced hepatocellular carcinoma. Am J Cancer Res 2022; 12:1606-1620. [PMID: 35530291 PMCID: PMC9077059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 03/23/2022] [Indexed: 06/14/2023] Open
Abstract
Anti-Programmed cell Death protein 1 (Anti-PD1) or Programmed Death-Ligand 1 (PDL1) immune checkpoint inhibitors provide treatment options for advanced HCC patients with low response rates. Combination therapy is becoming a major issue to improve the unmet need. Proton beam radiotherapy (PBT) could effectively control the local tumor with a low-risk injury to peripheral liver parenchyma. We retrospectively reviewed the patients who have received PBT combined with anti-PD1/PDL1 to evaluate the efficacy and safety of the advanced HCC patients. This study reviewed 29 advanced HCC patients who have received PBT and anti-PD1/PDL1 during 2016 and 2019. All were Child-Pugh A and performance status 0-1. Seventeen patients (58.6%) had extrahepatic spreading. Concurrent PBT started during anti-PD1/PDL1 with a median of 96.6 grays equivalent dose. The PBT field covered all tumors in 13 (44.8%) patients under curative intent. Other patients (55.2%) received palliative PBT that covered only the principal tumors. All patients have completed the concurrent PBT protocol. The median anti-PD1/PDL1 duration was 3.9 months. After a median follow-up of 13.2 months, the rates of 1-year PBT infield tumor control, 1-year outfield tumor control, and overall response were 90.5%, 90.9%, and 61.5%, and 70.8%, 69.2%, and 43.8%, respectively for curative-intent and palliative-control PBT. Complete response was found in 4 (30.8%) curative-intent and 1 (6.3%) palliative-control patients. The median overall progression-free survival was 27.2 months for curative-intent patients and 15.9 months for palliative-control patients. The overall survival was non-reached for both groups. The ALBI grade and Child-Pugh score change at 3-month and 6-month after PBT initiation were nonsignificant. No unexpected adverse event occurred except nine patients (31.0%) had treatment-related adverse events higher than or equal to Grade 3, including 2 (6.9%) had a radiation-induced liver injury. PBT combined with anti-PD1/PDL1 was safe without unexpected adverse events. The concurrent therapy could effectively treat advanced HCC through sustained local tumor necrosis and effective systemic tumor control for the patients who received curative-intent or palliative-control PBT combined with anti-PD1/PDL1.
Collapse
Affiliation(s)
- Chung-Wei Su
- Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Ming-Mo Hou
- Department of Oncology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Pei-Wei Huang
- Department of Oncology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Yung-Chih Chou
- Department of Radiation Oncology, Proton and Radiotherapy Center, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Bing-Shen Huang
- Department of Radiation Oncology, Proton and Radiotherapy Center, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Jeng-Hwei Tseng
- Department of Medical Imaging & Intervention, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Chao-Wei Hsu
- Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Tung-Chieh Chang
- Department of Radiation Oncology, Proton and Radiotherapy Center, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Chang Gung UniversityTaiwan
| |
Collapse
|
|
16
|
Lee CH, Chen AH, Hung SP, Hsieh CE, Tseng JH, Chen PJ, Cheng JY, Chang JTC, Chan KM, Lin SM, Lin CC, Chen WT, Chen WY, Huang BS. Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion. Cancers (Basel) 2022; 14:1616. [PMID: 35406392 PMCID: PMC8997051 DOI: 10.3390/cancers14071616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/12/2022] [Accepted: 03/21/2022] [Indexed: 12/07/2022] Open
Abstract
Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.
Collapse
Affiliation(s)
- Ching-Hsin Lee
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
| | - An-Hsin Chen
- Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (A.-H.C.); (J.-H.T.)
| | - Sheng-Ping Hung
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
| | - Cheng-En Hsieh
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
- Cancer Biology and Immunology Programs, Graduate School of Biomedical Sciences, University of Texas MD Anderson UTHealth, Houston, TX 77030, USA
| | - Jeng-Hwei Tseng
- Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (A.-H.C.); (J.-H.T.)
| | - Po-Jui Chen
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
| | - Jen-Yu Cheng
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, Taiwan;
| | - Joseph Tung-Chieh Chang
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
| | - Kun-Ming Chan
- Department of General Surgery, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan;
| | - Shi-Ming Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (S.-M.L.); (C.-C.L.); (W.-T.C.)
| | - Chen-Chun Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (S.-M.L.); (C.-C.L.); (W.-T.C.)
| | - Wei-Ting Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (S.-M.L.); (C.-C.L.); (W.-T.C.)
| | - Wan-Yu Chen
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei City 100225, Taiwan;
- Cancer Research Center, National Taiwan University College of Medicine, Taipei City 100225, Taiwan
| | - Bing-Shen Huang
- Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and University, Taoyuan City 333423, Taiwan; (C.-H.L.); (S.-P.H.); (C.-E.H.); (P.-J.C.); (J.T.-C.C.)
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung City 83301, Taiwan;
- Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan City 333323, Taiwan
| |
Collapse
|
|
17
|
Shen PC, Huang WY, Dai YH, Lo CH, Yang JF, Su YF, Wang YF, Lu CF, Lin CS. Radiomics-Based Predictive Model of Radiation-Induced Liver Disease in Hepatocellular Carcinoma Patients Receiving Stereo-Tactic Body Radiotherapy. Biomedicines 2022; 10:biomedicines10030597. [PMID: 35327398 PMCID: PMC8945465 DOI: 10.3390/biomedicines10030597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/27/2022] [Accepted: 03/01/2022] [Indexed: 11/16/2022] Open
Abstract
(1) Background: The application of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) limited the risk of the radiation-induced liver disease (RILD) and we aimed to predict the occurrence of RILD more accurately. (2) Methods: 86 HCC patients were enrolled. We identified key predictive factors from clinical, radiomic, and dose-volumetric parameters using a multivariate analysis, sequential forward selection (SFS), and a K-nearest neighbor (KNN) algorithm. We developed a predictive model for RILD based on these factors, using the random forest or logistic regression algorithms. (3) Results: Five key predictive factors in the training set were identified, including the albumin–bilirubin grade, difference average, strength, V5, and V30. After model training, the F1 score, sensitivity, specificity, and accuracy of the final random forest model were 0.857, 100, 93.3, and 94.4% in the test set, respectively. Meanwhile, the logistic regression model yielded an F1 score, sensitivity, specificity, and accuracy of 0.8, 66.7, 100, and 94.4% in the test set, respectively. (4) Conclusions: Based on clinical, radiomic, and dose-volumetric factors, our models achieved satisfactory performance on the prediction of the occurrence of SBRT-related RILD in HCC patients. Before undergoing SBRT, the proposed models may detect patients at high risk of RILD, allowing to assist in treatment strategies accordingly.
Collapse
Affiliation(s)
- Po-Chien Shen
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
| | - Wen-Yen Huang
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 114, Taiwan
| | - Yang-Hong Dai
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
| | - Cheng-Hsiang Lo
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
| | - Jen-Fu Yang
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
- National Defense Medical Center, Institute of Medical Science, Taipei 114, Taiwan
| | - Yu-Fu Su
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
- National Defense Medical Center, Institute of Medical Science, Taipei 114, Taiwan
| | - Ying-Fu Wang
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
| | - Chia-Feng Lu
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- Correspondence: (C.-F.L.); (C.-S.L.); Tel.: +886-2-2826-7308 (C.-F.L.); +886-2-8792-7122 (C.-S.L.)
| | - Chun-Shu Lin
- National Defense Medical Center, Department of Radiation Oncology, Tri-Service General Hospital, Taipei 114, Taiwan; (P.-C.S.); (W.-Y.H.); (Y.-H.D.); (C.-H.L.); (J.-F.Y.); (Y.-F.S.); (Y.-F.W.)
- Correspondence: (C.-F.L.); (C.-S.L.); Tel.: +886-2-2826-7308 (C.-F.L.); +886-2-8792-7122 (C.-S.L.)
| |
Collapse
|
|
18
|
Choe JW, Lee HY, Rim CH. Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis? World J Gastroenterol 2022; 28:704-714. [PMID: 35317274 PMCID: PMC8891726 DOI: 10.3748/wjg.v28.i7.704] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 12/17/2021] [Accepted: 01/19/2022] [Indexed: 02/06/2023] Open
Abstract
Portal invasion of hepatocellular carcinoma (HCC) occurs in 12.5%-40% of patients diagnosed with cancer and yields poor clinical outcomes. Since it is a common cause of inoperability, sorafenib was regarded as the standard treatment for HCC in the Barcelona Clinic of Liver Cancer guidelines. However, the median survival of the Asian population was only approximately 6 mo, and the tumor response rate was less than moderate (< 5%). Various locoregional modalities were performed, including external beam radiotherapy (EBRT), transarterial chemoembolization, hepatic arterial infusion chemotherapy, and surgery, alone or in combination. Among them, EBRT is a noninvasive method and can safely treat tumors involving the major vessels. Palliative EBRT has been commonly performed, especially in East Asian countries, where locally invasive HCC is highly prevalent. Although surgery is not commonly indicated, pioneering studies have demonstrated encouraging results in recent decades. Furthermore, the combination of neo- or adjuvant EBRT and surgery has been recently used and has significantly improved the outcomes of HCC patients, as reported in a few randomized studies. Regarding systemic modality, a combination of novel immunotherapy and vascular endothelial growth factor inhibitor showed results superior to that of sorafenib as a first-line agent. Future clinical trials investigating the combined use of these novel agents, surgery, and EBRT are expected to improve the prognosis of HCC with portal invasion.
Collapse
Affiliation(s)
- Jung Wan Choe
- Department ofInternal Medicine, Korea University Ansan Hospital, Ansan 15355, South Korea
| | - Hye Yoon Lee
- Department of Surgery, Korea University Ansan Hospital, Ansan 15355, South Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan 15355, South Korea
| |
Collapse
|
|
19
|
Li Y, Li X, Yang J, Wang S, Tang M, Xia J, Gao Y. Flourish of Proton and Carbon Ion Radiotherapy in China. Front Oncol 2022; 12:819905. [PMID: 35237518 PMCID: PMC8882681 DOI: 10.3389/fonc.2022.819905] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/24/2022] [Indexed: 11/13/2022] Open
Abstract
Proton and heavy ion therapy offer superior relative biological effectiveness (RBE) in the treatment of deep-seated tumors compared with conventional photon radiotherapy due to its Bragg-peak feature of energy deposition in organs. Many proton and carbon ion therapy centers are active all over the world. At present, five particle radiotherapy institutes have been built and are receiving patient in China, mainly including Wanjie Proton Therapy Center (WPTC), Shanghai Proton Heavy Ion Center (SPHIC), Heavy Ion Cancer Treatment Center (HIMM), Chang Gung Memorial Hospital (CGMH), and Ruijin Hospital affiliated with Jiao Tong University. Many cancer patients have benefited from ion therapy, showing unique advantages over surgery and chemotherapy. By the end of 2020, nearly 8,000 patients had been treated with proton, carbon ion or carbon ion combined with proton therapy. So far, there is no systemic review for proton and carbon ion therapy facility and clinical outcome in China. We reviewed the development of proton and heavy ion therapy, as well as providing the representative clinical data and future directions for particle therapy in China. It has important guiding significance for the design and construction of new particle therapy center and patients’ choice of treatment equipment.
Collapse
Affiliation(s)
- Yue Li
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- *Correspondence: Yue Li,
| | - Xiaoman Li
- Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Jiancheng Yang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
| | - Sicheng Wang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
| | - Meitang Tang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
| | - Jiawen Xia
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- Huizhou Research Center of Ion Science, Chinese Academy of Sciences, Huizhou, China
| | - Yunzhe Gao
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, China
| |
Collapse
|
|
20
|
Chen CL, Ong AD, Cheng JY, Yong CC, Lin CC, Chen CY, Cheng YF. Proton beam therapy to bridge or downstage locally advanced hepatocellular carcinoma to living donor liver transplantation. Hepatobiliary Surg Nutr 2022; 11:103-111. [PMID: 35284524 DOI: 10.21037/hbsn-21-379] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/16/2021] [Indexed: 12/11/2022]
Affiliation(s)
- Chao-Long Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Aldwin D Ong
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Jen-Yu Cheng
- Liver Transplantation Center, Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Chee-Chien Yong
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Chih-Che Lin
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Chih-Yi Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| | - Yu-Fan Cheng
- Liver Transplantation Center, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, China
| |
Collapse
|
|
21
|
Akinduro OO, De Biase G, Goyal A, Meyer JH, Sandhu SJS, Kowalchuk RO, Trifiletti DM, Sheehan J, Merrell KW, Vora SA, Broderick DF, Clarke MJ, Bydon M, McClendon J, Kalani MA, Quiñones-Hinojosa A, Abode-Iyamah K. Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis? J Neurooncol 2022; 156:329-339. [PMID: 34993721 DOI: 10.1007/s11060-021-03915-3] [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: 10/26/2021] [Accepted: 11/26/2021] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed. METHODS We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timing and radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes. RESULTS After review of 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043). CONCLUSION Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.
Collapse
Affiliation(s)
| | - Gaetano De Biase
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA
| | - Anshit Goyal
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA
| | - Jenna H Meyer
- Department of Neurosurgery, Mayo Clinic, Phoenix, AZ, USA
| | | | | | | | - Jason Sheehan
- Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA
| | | | - Sujay A Vora
- Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA
| | | | | | - Mohamad Bydon
- Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA
| | | | | | | | | |
Collapse
|
|
22
|
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]
|
|
23
|
Moteabbed M, Smeets J, Hong TS, Janssens G, Labarbe R, Wolfgang JA, Bortfeld TR. Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors. Phys Med Biol 2021; 66. [PMID: 34407528 DOI: 10.1088/1361-6560/ac1ef2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 08/18/2021] [Indexed: 12/25/2022]
Abstract
Magnetic resonance imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice cone-beam CT (CBCT)-guided PT, and other MR-guided methods, i.e. offline MR-guided PT and MR-linac, for treatment of liver tumors. Clinical outcomes were assessed by quantifying the dosimetric and biological impact of target margin reduction enabled by each image-guided approach. Planning target volume (PTV) margins were calculated using random and systematic setup, delineation and motion uncertainties, which were quantified by analyzing longitudinal MRI data for 10 patients with liver tumors. Proton treatment plans were created using appropriate PTV margins for each image-guided PT method. Photon plans with margins equivalent to MRiPT were generated to represent MR-linac. Normal tissue complication probabilities (NTCP) of the uninvolved liver were compared. We found that PTV margin can be reduced by 20% and 40% for offline MR-guided PT and MRiPT, respectively, compared with CBCT-guided PT. Furthermore, clinical target volume expansion could be largely alleviated when delineating on MRI rather than CT. Dosimetric implications included decreased equivalent mean dose of the uninvolved liver, i.e. up to 24.4 Gy and 27.3 Gy for offline MR-guided PT and MRiPT compared to CBCT-guided PT, respectively. Considering Child-Pugh score increase as endpoint, NTCP of the uninvolved liver was significantly decreased for MRiPT compared to CBCT-guided PT (up to 48.4%,p < 0.01), offline MR-guided PT (up to 12.9%,p < 0.01) and MR-linac (up to 30.8%,p < 0.05). Target underdose was possible in the absence of MRI-guidance (D90 reduction up to 4.2 Gy in 20% of cases). In conclusion, MRiPT has the potential to significantly reduce healthy liver toxicities in patients with liver tumors. It is superior to other image-guided techniques currently available.
Collapse
Affiliation(s)
- Maryam Moteabbed
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| | | | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| | | | - Rudi Labarbe
- Ion Beam Applications, Louvain-La-Neuve, Belguim
| | - John A Wolfgang
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| | - Thomas R Bortfeld
- Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America
| |
Collapse
|
|
24
|
Walter F, Fuchs F, Gerum S, Rottler MC, Erdelkamp R, Neumann J, Nierer L, Guba M, De Toni EN, Seidensticker M, Ricke J, Belka C, Corradini S. HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience. Front Oncol 2021; 11:717792. [PMID: 34513694 PMCID: PMC8426600 DOI: 10.3389/fonc.2021.717792] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/03/2021] [Indexed: 12/24/2022] Open
Abstract
Background In the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT). Methods All patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT. Results A total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47–311) after BT and 202 days (range 44–775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT. Conclusion Both SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.
Collapse
Affiliation(s)
- Franziska Walter
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Frederik Fuchs
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Sabine Gerum
- Department of Radiation Oncology, Landeskrankenhaus Salzburg, Uniklinikum der Paracelsus Medizinischen Universität, Salzburg, Austria
| | - Maya C Rottler
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Robert Erdelkamp
- Department of Pathology, University Hospital, LMU Munich, Munich, Germany
| | - Jens Neumann
- Department of Pathology, University Hospital, LMU Munich, Munich, Germany
| | - Lukas Nierer
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Markus Guba
- Department of Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Enrico N De Toni
- Department of Gastroenterology, University Hospital, LMU Munich, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| |
Collapse
|
|
25
|
Bhangoo RS, Mullikin TC, Ashman JB, Cheng TW, Golafshar MA, DeWees TA, Johnson JE, Shiraishi S, Liu W, Hu Y, Merrell KW, Haddock MG, Krishnan S, Rule WG, Sio TT, Hallemeier CL. Intensity Modulated Proton Therapy for Hepatocellular Carcinoma: Initial Clinical Experience. Adv Radiat Oncol 2021; 6:100675. [PMID: 34409199 PMCID: PMC8361033 DOI: 10.1016/j.adro.2021.100675] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/14/2021] [Accepted: 02/10/2021] [Indexed: 02/08/2023] Open
Abstract
Purpose Our purpose was to assess the safety and efficacy of intensity modulated proton therapy (IMPT) for the treatment of hepatocellular carcinoma (HCC). Methods and Materials A retrospective review was conducted on all patients who were treated with IMPT for HCC with curative intent from June 2015 to December 2018. All patients had fiducials placed before treatment. Inverse treatment planning used robust optimization with 2 to 3 beams. The majority of patients were treated in 15 fractions (n = 30, 81%, 52.5-67.5 Gy, relative biological effectiveness), whereas the remainder were treated in 5 fractions (n = 7, 19%, 37.5-50 Gy, relative biological effectiveness). Daily image guidance consisted of orthogonal kilovoltage x-rays and use of a 6° of freedom robotic couch. Outcomes (local control, progression free survival, and overall survival) were determined using Kaplan-Meier methods. Results Thirty-seven patients were included. The median follow-up for living patients was 21 months (Q1-Q3, 17-30 months). Pretreatment Child-Pugh score was A5-6 in 70% of patients and B7-9 in 30% of patients. Nineteen patients had prior liver directed therapy for HCC before IMPT. Eight patients (22%) required a replan during treatment, most commonly due to inadequate clinical target volume coverage. One patient (3%) experienced a grade 3 acute toxicity (pain) with no recorded grade 4 or 5 toxicities. An increase in Child-Pugh score by ≥ 2 within 3 months of treatment was observed in 6 patients (16%). At 1 year, local control was 94%, intrahepatic control was 54%, progression free survival was 35%, and overall survival was 78%. Conclusions IMPT is safe and feasible for treatment of HCC.
Collapse
Affiliation(s)
- Ronik S Bhangoo
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Trey C Mullikin
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Tiffany W Cheng
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | | - Todd A DeWees
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona.,Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona
| | | | - Satomi Shiraishi
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Wei Liu
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Yanle Hu
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | | | | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida
| | - William G Rule
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - Terence T Sio
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | |
Collapse
|
|
26
|
Iizumi T, Okumura T, Sekino Y, Takahashi H, Tsai YL, Takizawa D, Ishida T, Hiroshima Y, Nakamura M, Shimizu S, Saito T, Numajiri H, Mizumoto M, Nakai K, Sakurai H. Long-term clinical outcomes of patients receiving proton beam therapy for caudate lobe hepatocellular carcinoma. JOURNAL OF RADIATION RESEARCH 2021; 62:682-687. [PMID: 34036362 PMCID: PMC8273797 DOI: 10.1093/jrr/rrab040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/27/2021] [Indexed: 05/09/2023]
Abstract
Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0-152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P < 0.01), having a single tumour (P = 0.02) and a low serum alpha-fetoprotein level (AFP; P < 0.01) were significant factors predicting longer survival. The local control (LC) rates at one, three and five years were 100%, 85.9% and 85.9%, respectively, while the corresponding progression-free survival (PFS) rates were 65%, 27.5% and 22%, respectively. No grade 3 or worse adverse events were observed. PBT is effective and safe for the treatment of caudate HCC, and should therefore be considered a feasible option for intervention in patients with this disease.
Collapse
Affiliation(s)
- Takashi Iizumi
- Corresponding author. Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan. TEL: +81-29-853-7100; FAX: +81-29-853-7102; E-mail:
| | - Toshiyuki Okumura
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Yuta Sekino
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Hiroaki Takahashi
- Department of Diagnostic Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | - Yu-Lun Tsai
- Department of Radiation Oncology, Cathay General Hospital, Taipei, 106, Taiwan
| | - Daichi Takizawa
- Department of Radiation Oncology, Hitachi General Hospital, Ibaraki, 317-0077, Japan
| | - Toshiki Ishida
- Department of Radiation Therapy, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, Ibaraki, 309-1793, Japan
| | - Yuichi Hiroshima
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Masatoshi Nakamura
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Shosei Shimizu
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Takashi Saito
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Haruko Numajiri
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Masashi Mizumoto
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Kei Nakai
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology and Proton Medical Research Centre, University of Tsukuba, Ibaraki 305-8576, Japan
| |
Collapse
|
|
27
|
Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells. Cells 2021; 10:cells10030554. [PMID: 33806487 PMCID: PMC7999709 DOI: 10.3390/cells10030554] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 12/12/2022] Open
Abstract
Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Panobinostat increased G2/M arrest and production of intracellular reactive oxygen species, which was further enhanced by proton irradiation. Immunofluorescence staining of γH2AX showed that panobinostat enhanced proton-induced DNA damage. Panobinostat dose-dependently decreased expression of an anti-apoptotic protein, Mcl-1, concomitant with increasing acetylation of histone H4. The combination of panobinostat with proton irradiation enhanced apoptotic cell death to a greater extent than that with X-ray irradiation. Depletion of Mcl-1 by RNA interference enhanced proton-induced apoptosis and proton radiosensitization, suggesting a potential role of Mcl-1 in determining proton sensitivity. Together, our findings suggest that panobinostat may be a promising combination agent for proton beam therapy in HCC treatment.
Collapse
|