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For: Yoo GS, Yu JI, Park HC. Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives. World J Gastroenterol 2018; 24(28): 3090-3100 [PMID: 30065555 DOI: 10.3748/wjg.v24.i28.3090] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

For:	Yoo GS, Yu JI, Park HC. Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives. World J Gastroenterol 2018; 24(28): 3090-3100 [PMID: 30065555 DOI: 10.3748/wjg.v24.i28.3090] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] Open

Number

Cited by Other Article(s)

Xing S, Correa-Alfonso CM, Shin J, Pursley J, Depauw N, Domal S, Withrow J, Bolch W, Grassberger C, Paganetti H. Evaluating the Impact of Liver Vasculature Model Complexity for Estimating Dose to Circulating Blood During Radiation Therapy. Int J Radiat Oncol Biol Phys 2025;121:1339-1348. [PMID: 39608610 PMCID: PMC11911079 DOI: 10.1016/j.ijrobp.2024.11.087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 10/15/2024] [Accepted: 11/08/2024] [Indexed: 11/30/2024]

Abstract

PURPOSE

To assess the impact of liver model complexity on the estimated radiation dose to circulating blood during radiation therapy.

METHODS AND MATERIALS

Six patients with hepatocellular carcinoma (HCC) were selected covering a range of clinical treatment volume (CTV) sizes and locations. Photon and proton treatment plans were generated for each patient. Planning computed tomography, CTV contours, and dose distributions were deformably registered to the reference livers provided by the International Commission on Radiological Protection report. Three vasculature models were considered: (1) main vascular tree (MVT), (2) coarse vascular tree (CVT) of 1045 vessels, and (3) detailed vascular tree (DVT) of 2041 vessels. Blood dose-volume histograms (bDVHMVT, bDVHCVT, and bDVHDVT) and the mean circulating blood dose (μb,MVT, μb,CVT, and μb,DVT) were estimated using Monte Carlo simulations for all 3 models. The effect of varying blood velocity (vb) in HCC tumors on dose estimation was also evaluated through increasing the tumor vb by 1.5, 2, and 4.2 times.

RESULTS

For the 3 lesions located in the left lobe, the estimated μb,MVT was lower than μb,DVT by an average ± standard deviation of (6 ± 4)% and (17 ± 7)% for photon and proton treatments, respectively. Smaller differences were found for lesions in the right lobe, where μb,MVT was on average (2 ± 1)% lower than μb,DVT for photon and (3 ± 1)% lower for proton treatments. More pronounced difference between μb,MVT and μb,DVT was seen in lesions with smaller CTV sizes. We also found that considering the elevated tumor vb led to a reduction of estimated dose to circulating blood, with a maximum reduction in the estimated μb of 39% and 8% for CTV of 603 and 249 mL, respectively.

CONCLUSION

Our study revealed that the impact of liver vasculature model complexity on the estimated dose to blood depended on lesion-specific characteristics. For lesions with larger CTV size on the right liver lobe treated with photons, modeling only major vessels could generate bDVHs that are dosimetrically comparable with bDVHs of more complex vascular models. Increased tumor vb resulted in a reduction of the estimated blood dose.

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Sharma D, Khosla D, Meena BL, Yadav HP, Kapoor R. Exploring the Evolving Landscape of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma. J Clin Exp Hepatol 2025;15:102386. [PMID: 39282593 PMCID: PMC11399579 DOI: 10.1016/j.jceh.2024.102386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 07/29/2024] [Indexed: 09/19/2024] Open

Abstract

Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80-90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.

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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]

Chen CY, Huang BS, Hong JH, Chang JTC, Chen MC, Tang WR, Shun SC, Chen ML. Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy. J Nurs Res 2024;32:e319. [PMID: 38506576 DOI: 10.1097/jnr.0000000000000606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2024] Open

Lee PY, Huang BS, Lee SH, Chan TY, Yen E, Lee TF, Cho IC. An investigation into the impact of volumetric rescanning and fractionation treatment on dose homogeneity in liver cancer proton therapy. JOURNAL OF RADIATION RESEARCH 2024;65:100-108. [PMID: 38037473 PMCID: PMC10803156 DOI: 10.1093/jrr/rrad093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 09/16/2023] [Indexed: 12/02/2023]

Affiliation(s)

Pei-Yi Lee Proton and Radiation Therapy Center, Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, No. 129, Dapi Rd., Niaosong Dist., Kaohsiung City, 833401, Taiwan
Bing-Shen Huang Proton and Radiation Therapy Center, Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, No. 129, Dapi Rd., Niaosong Dist., Kaohsiung City, 833401, Taiwan Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital, No. 15, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333011, Taiwan Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333323, Taiwan Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333323, Taiwan
Shen-Hao Lee Proton and Radiation Therapy Center, Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital, No. 15, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333011, Taiwan
Tsz-Yui Chan Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333323, Taiwan
Eric Yen Institute of Physics, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nangang Dist., Taipei City, 115201, Taiwan
Tsair-Fwu Lee Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University of Science and Technology, No. 415, Jiangong Rd., Sanmin Dist., Kaohsiung City, 807618, Taiwan
I-Chun Cho Research Center for Radiation Medicine, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 333323, Taiwan Institute for Radiological Research, Chang Gung University, No. 259, Wenhua 1st Rd., Guishan Dist., Taiwan Taoyuan City, 333323 Taiwan

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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

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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Chami P, Diab Y, Khalil DN, Azhari H, Jarnagin WR, Abou-Alfa GK, Harding JJ, Hajj J, Ma J, El Homsi M, Reyngold M, Crane C, Hajj C. Radiation and Immune Checkpoint Inhibitors: Combination Therapy for Treatment of Hepatocellular Carcinoma. Int J Mol Sci 2023;24:16773. [PMID: 38069095 PMCID: PMC10706661 DOI: 10.3390/ijms242316773] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/24/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open

Li X, Ma Z, Mei L. Comprehensive analysis of UBE2C expression and its potential roles and mechanisms in hepatocellular carcinoma. Aging (Albany NY) 2023;15:7397-7407. [PMID: 37580802 PMCID: PMC10457065 DOI: 10.18632/aging.204792] [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: 09/01/2022] [Accepted: 05/01/2023] [Indexed: 08/16/2023]

Bae BK, Yu JI, Park HC, Goh MJ, Paik YH. Radiotherapy trend in elderly hepatocellular carcinoma: retrospective analysis of patients diagnosed between 2005 and 2017. Radiat Oncol J 2023;41:98-107. [PMID: 37403352 DOI: 10.3857/roj.2023.00353] [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: 04/20/2023] [Accepted: 05/19/2023] [Indexed: 07/06/2023] Open

Chen MF, Chen PT, Hsieh CC, Wang CC. Effect of Proton Therapy on Tumor Cell Killing and Immune Microenvironment for Hepatocellular Carcinoma. Cells 2023;12:cells12020332. [PMID: 36672266 PMCID: PMC9857172 DOI: 10.3390/cells12020332] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/31/2022] [Accepted: 01/13/2023] [Indexed: 01/19/2023] Open

Abstract

Radiotherapy with proton therapy (PT) has dosimetric advantages over photon therapy, which helps to enlarge the therapeutic window of radiotherapy for hepatocellular carcinoma (HCC). We evaluated the response of HCC to PT and examined the underlying mechanisms. The human liver cancer cell lines HepG2 and HuH7 and the murine liver cancer cell line Hepa1-6 were selected for cell and animal experiments to examine the response induced by PT irradiation. Biological changes and the immunological response following PT irradiation were examined. In vitro experiments showed no significant difference in cell survival following PT compared with photon radiotherapy. In a murine tumor model, the tumors were obviously smaller in size 12 days after PT irradiation. The underlying changes included increased DNA damage, upregulated IL-6 levels, and a regulated immune tumor microenvironment. Protein analysis in vitro and in vivo showed that PT increased the level of programmed cell death ligand 1 (PD-L1) expressed in tumor cells and recruited myeloid-derived suppressor cells (MDSCs). The increase in PD-L1 was positively correlated with the irradiation dose. In Hepa1-6 syngeneic mouse models, the combination of PT with anti-PD-L1 increased tumor growth delay compared with PT alone, which was associated with increased tumor-infiltrating T cells and attenuated MDSC recruitment in the microenvironment. Furthermore, when PT was applied to the primary HCC tumor, anti-PD-L1 antibody-treated mice showed smaller synchronous unirradiated tumors. In conclusion, the response of HCC to PT was determined by tumor cell killing and the immunological response in the tumor microenvironment. The combination with the anti-PD-L1 antibody to enhance antitumor immunity was responsible for the therapeutic synergism for HCC treated with PT. Based on our results, we suggest that PT combined with anti-PD-L1 may be a promising therapeutic policy for HCC.

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Nankali S, Worm ES, Thomsen JB, Stick LB, Bertholet J, Høyer M, Weber B, Mortensen HR, Poulsen PR. Intrafraction tumor motion monitoring and dose reconstruction for liver pencil beam scanning proton therapy. Front Oncol 2023;13:1112481. [PMID: 36937392 PMCID: PMC10019817 DOI: 10.3389/fonc.2023.1112481] [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: 11/30/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open

Abstract

Background

Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions.

Methods

Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D 2 % - D 98 % D 50 % × 100 % .

Results

The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions.

Conclusions

A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.

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Răileanu M, Straticiuc M, Iancu DA, Andrei RF, Radu M, Bacalum M. Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells. J Struct Biol 2022;214:107919. [PMID: 36356881 DOI: 10.1016/j.jsb.2022.107919] [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: 05/08/2022] [Revised: 10/31/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022]

Bae BK, Park HC, Yu JI, Yoo GS, Sinn DH, Choi MS, Oh JH. Trends in radiotherapy administration in the management of hepatocellular carcinoma: Analysis of a Korean tertiary hospital registry of hepatocellular carcinoma patients diagnosed between 2005 and 2017. Front Oncol 2022;12:928119. [PMID: 35936747 PMCID: PMC9355731 DOI: 10.3389/fonc.2022.928119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/30/2022] [Indexed: 11/15/2022] Open

Abstract

Purpose

To present the trends in radiotherapy for the management of hepatocellular carcinoma (HCC) at a single tertiary referral hospital in South Korea.

Materials and Methods

We retrospectively reviewed prospectively collected registry data of patients newly diagnosed with HCC between January 2005 and December 2017 at the Samsung Medical Center. Trends in radiotherapy, delivery techniques, tumor stage, and age were evaluated.

Results

During the study period, 9,132 patients were newly diagnosed with HCC at our institution. Of these, 2,445 patients (26.8%) received radiotherapy for all lesions, including extrahepatic metastases; 1,865 patients (20.4%) received radiotherapy for intrahepatic lesions alone, and 469 patients (5.1%) received radiotherapy as initial management. Although the proportion of patients receiving radiotherapy increased slightly over the study period (24.2% vs. 26.6%), the proportions of patients receiving radiotherapy for intrahepatic lesions (16.8% vs. 21.9%) and as initial management (0.1% vs. 12.5%) increased dramatically. The majority of patients treated between 2005 and 2008 received three-dimensional conformal radiotherapy (56.3%), whereas the majority of patients treated between 2018 and 2021 received proton beam therapy (43.6%). With the technical developments, the overall survival (OS) of patients who received radiotherapy as initial management increased significantly (5-year OS: from 5.4% to 30.1%), and the OS difference between patients who did and did not receive radiotherapy as initial management significantly decreased (ratio of restricted mean survival time: from 0.383 to 0.544).

Conclusion

This registry-based, retrospective study indicated an increasing trend in the utilization of radiotherapy, adoption of advanced radiotherapy techniques, and OS improvements in patients with HCC.

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Lee B, Cho S, Park HC, Kang SW, Kim JS, Chung JB. Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma. Radiat Oncol 2022;17:125. [PMID: 35842636 PMCID: PMC9288675 DOI: 10.1186/s13014-022-02100-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 07/09/2022] [Indexed: 11/10/2022] Open

Abstract

BACKGROUND

The present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.

METHODS

With computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior-posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles (0°, 45°, and 90°). Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.

RESULTS

Percentage differences in the dosimetric parameters calculated by MC ranged from - 7.0 to 3.9% for the photon plan and - 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (D_min), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.

CONCLUSIONS

Dose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose.

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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

Zhao W, Jiang X, Weisenthal K, Ma J, Botticelli EM, Zhou Y, Hedley-Whyte ET, Wang B, Swearingen B, Soberman RJ, Klibanski A, Zhang X. High Histone Deacetylase 2/3 Expression in Non-Functioning Pituitary Tumors. Front Oncol 2022;12:875122. [PMID: 35646715 PMCID: PMC9136140 DOI: 10.3389/fonc.2022.875122] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 04/13/2022] [Indexed: 11/21/2022] Open

Lewis S, Dawson L, Barry A, Stanescu T, Mohamad I, Hosni A. Stereotactic body radiation therapy for hepatocellular carcinoma: from infancy to ongoing maturity. JHEP Rep 2022;4:100498. [PMID: 35860434 PMCID: PMC9289870 DOI: 10.1016/j.jhepr.2022.100498] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 04/23/2022] [Accepted: 04/25/2022] [Indexed: 12/16/2022] Open

Xing S, Shin J, Pursley J, Correa-Alfonso CM, Depauw N, Domal S, Withrow J, Bolch W, Grassberger C, Paganetti H. A dynamic blood flow model to compute absorbed dose to circulating blood and lymphocytes in liver external beam radiotherapy. Phys Med Biol 2022;67:10.1088/1361-6560/ac4da4. [PMID: 35061601 PMCID: PMC8985306 DOI: 10.1088/1361-6560/ac4da4] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/21/2022] [Indexed: 01/01/2023]

Abstract

We have developed a novel 4D dynamic liver blood flow model, capable of accurate dose estimation to circulating blood cells during liver-directed external beam radiotherapy, accounting for blood recirculation and radiation delivery time structure. Adult male and adult female liver computational phantoms with detailed vascular trees were developed to include the hepatic arterial, hepatic portal venous, and hepatic venous trees. A discrete time Markov Chain approach was applied to determine the spatiotemporal distribution of 105blood particles (BP) in the human body based on reference values for cardiac output and organ blood volumes. For BPs entering the liver, an explicit Monte Carlo simulation was implemented to track their propagation along ∼2000 distinct vascular pathways through the liver. The model tracks accumulated absorbed dose from time-dependent radiation fields with a 0.1 s time resolution. The computational model was then evaluated for 3 male and 3 female patients receiving photon (VMAT and IMRT) and proton (passive SOBP and active PBS) treatments. The dosimetric impact of treatment modality, delivery time, and fractionation on circulating blood cells was investigated and quantified using the mean dose (μdose,b),V>0Gy,V>0.125Gy,andD2%. Average reductions inμdose,b,V>0Gy,V>0.125GyandD2%of 45%, 6%, 53%, 19% respectively, were observed for proton treatments as compared to photon treatments. Our simulation also showed thatV>0Gy,V>0.125Gy, andD2%were highly sensitive to the beam-on time. BothV>0GyandV>0.125Gyincreased with beam-on time, whereasD2%decreased with increasing beam-on time, demonstrating the tradeoff between low dose to a large fraction of blood cells and high dose to a small fraction of blood cells. Consequently, proton treatments are not necessarily advantageous in terms of dose to the blood simply based on integral dose considerations. Instead, both integral dose and beam-on time can substantially impact relevant dosimetric indices.

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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]

Subramanian S, Mallia MB, Shinto AS, Mathew AS. Clinical Management of Liver Cancer in India and Other Developing Nations: A Focus on Radiation Based Strategies. Oncol Ther 2021;9:273-295. [PMID: 34046873 PMCID: PMC8593115 DOI: 10.1007/s40487-021-00154-4] [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: 02/24/2021] [Accepted: 05/12/2021] [Indexed: 11/28/2022] Open

Worm ES, Hansen R, Høyer M, Weber B, Mortensen H, Poulsen PR. Uniform versus non-uniform dose prescription for proton stereotactic body radiotherapy of liver tumors investigated by extensive motion-including treatment simulations. Phys Med Biol 2021;66. [PMID: 34544071 DOI: 10.1088/1361-6560/ac2880] [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: 04/08/2021] [Accepted: 09/20/2021] [Indexed: 12/24/2022]

Abstract

Compared to x-ray-based stereotactic body radiotherapy (SBRT) of liver cancer, proton SBRT may reduce the normal liver tissue dose. For an optimal trade-off between target and liver dose, a non-uniform dose prescription is often applied in x-ray SBRT, but lacks investigation for proton SBRT. Also, proton SBRT is prone to breathing-induced motion-uncertainties causing target mishit or dose alterations by interplay with the proton delivery. This study investigated non-uniform and uniform dose prescription in proton-based liver SBRT, including effects of rigid target motion observed during planning-4DCT and treatment. The study was based on 42 x-ray SBRT fractions delivered to 14 patients under electromagnetic motion-monitoring. For each patient, a non-uniform and uniform proton plan were made. The uniform plan was renormalized to be iso-toxic with the non-uniform plan using a NTCP model for radiation-induced liver disease. The motion data were used in treatment simulations to estimate the delivered target dose with rigid motion. Treatment simulations were performed with and without a repainting scheme designed to mitigate interplay effects. Including rigid motion, the achieved CTV mean dose after three fractions delivered without repainting was on average (±SD) 24.8 ± 8.4% higher and the D_98%was 16.2 ± 11.3% higher for non-uniform plans than for uniform plans. The interplay-induced increase in D_2%relative to the static plans was reduced from 3.2 ± 4.1% without repainting to -0.5 ± 1.7% with repainting for non-uniform plans and from 1.5 ± 2.0% to 0.1 ± 1.3% for uniform plans. Considerable differences were observed between estimated CTV doses based on 4DCT motion and intra-treatment motion. In conclusion, non-uniform dose prescription in proton SBRT may provide considerably higher tumor doses than uniform prescription for the same complication risk. Due to motion variability, target doses estimated from 4DCT motion may not accurately reflect the delivered dose. Future studies including modelling of deformations and associated range uncertainties are warranted to confirm the findings.

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Kim KS, Wu HG. Who Will Benefit from Charged-Particle Therapy? Cancer Res Treat 2021;53:621-634. [PMID: 34176253 PMCID: PMC8291184 DOI: 10.4143/crt.2021.299] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open

Bajaj G, Sundaram K, Jambhekar K, Ram R. Imaging After Locoregional Therapy for Hepatocellular Carcinoma with Emphasis on LIRADS Treatment Response Assessment Criteria. Semin Ultrasound CT MR 2021;42:318-331. [PMID: 34130846 DOI: 10.1053/j.sult.2021.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]

Brasse D, Burckel H, Marchand P, Rousseau M, Ouadi A, Vanstalle M, Finck C, Laquerriere P, Boisson F. Comparison of the [¹⁸F]-FDG and [¹⁸F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma. Mol Imaging Biol 2021;23:724-732. [PMID: 33847900 DOI: 10.1007/s11307-021-01602-3] [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: 01/29/2021] [Revised: 03/26/2021] [Accepted: 03/31/2021] [Indexed: 11/28/2022]

Abstract

PURPOSE

The main objective of the present study was to compare the 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]-FDG) and 3'-[¹⁸F]fluoro-3'-deoxythymidine ([¹⁸F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC).

PROCEDURES

SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [¹⁸F]-FDG and [¹⁸F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10, and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every 3 days up to 16 days after irradiation.

RESULTS

[¹⁸F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [¹⁸F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [¹⁸F]-FDG normalized activity showed an 85% decrease (p < 0.01) for both 10 and 20 Gy doses and no variation for 5 Gy. Conversely, a significant 61% (p = 0.002) increase was observed for [¹⁸F]-FLT normalized activity at 5 Gy and no variation for higher doses.

CONCLUSION

We showed that the use of the [¹⁸F]-FDG and [¹⁸F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [¹⁸F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [¹⁸F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.

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Tsai YL, Takei H, Iizumi T, Okumura T, Sekino Y, Numajiri H, Ishikawa H, Sakae T, Sakurai H. Capacity of proton beams in preserving normal liver tissue during proton beam therapy for hepatocellular carcinoma. JOURNAL OF RADIATION RESEARCH 2021;62:133-141. [PMID: 33392617 PMCID: PMC7779355 DOI: 10.1093/jrr/rraa098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 08/26/2020] [Accepted: 09/29/2020] [Indexed: 06/12/2023]

Yoo GS, Ahn WG, Kim SY, Kang W, Choi C, Park HC. Radiation-induced abscopal effect and its enhancement by programmed cell death 1 blockade in the hepatocellular carcinoma: A murine model study. Clin Mol Hepatol 2020;27:144-156. [PMID: 33280350 PMCID: PMC7820196 DOI: 10.3350/cmh.2020.0095] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 08/26/2020] [Indexed: 02/06/2023] Open

Chen CP. Role of External Beam Radiotherapy in Hepatocellular Carcinoma. Clin Liver Dis 2020;24:701-717. [PMID: 33012454 DOI: 10.1016/j.cld.2020.07.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Yoo GS, Yu JI, Park HC, Hyun D, Jeong WK, Lim HY, Choi MS, Ha SY. Do Biliary Complications after Proton Beam Therapy for Perihilar Hepatocellular Carcinoma Matter? Cancers (Basel) 2020;12:cancers12092395. [PMID: 32847035 PMCID: PMC7565009 DOI: 10.3390/cancers12092395] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/13/2020] [Accepted: 08/17/2020] [Indexed: 12/21/2022] Open

Cheng JY, Liu CM, Wang YM, Hsu HC, Huang EY, Huang TT, Lee CH, Hung SP, Huang BS. Proton versus photon radiotherapy for primary hepatocellular carcinoma: a propensity-matched analysis. Radiat Oncol 2020;15:159. [PMID: 32605627 PMCID: PMC7325065 DOI: 10.1186/s13014-020-01605-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 06/23/2020] [Indexed: 12/18/2022] Open

Abstract

Background

Proton radiotherapy has a dosimetric advantage over photon radiotherapy. Many retrospective studies have shown promising results with proton radiotherapy in treating hepatocellular carcinoma (HCC). However, clinical evidence demonstrating the benefit of protons over photons is still limited. We therefore compared the clinical outcomes of the two modalities using medical research databases from our medical foundation.

Methods

We conducted a propensity score-matched cohort study based on our multi-institution medical organization research database. From January 2007 to January 2018, a total of 413 patients (photon: 349; proton: 64) who were diagnosed with HCC and primarily treated with radiotherapy with curative intent were enrolled. Overall survival (OS) and radiation-induced liver disease (RILD) were assessed. Stratified analysis was also performed to evaluate the heterogeneous effects of the two arms.

Results

A total of 110 patients (photon: 55; proton: 55) were analyzed in the propensity-matched series. The matched groups were balanced for baseline tumor risk factors. Cox regression analysis revealed a significant survival benefit in the proton group (p = 0.032, HR 0.56, 95% CI 0.33–0.96). The median overall survival in the proton group was not reached and that in the photon group was 17.4 months. The biological equivalent dose of radiotherapy was significantly higher in the proton group than in the photon group (median, 96.56 Gray [relative biological effectiveness] vs. 62.5 Gray, p < 0.001). The risk of RILD was significantly lower in the proton group (11.8% vs. 36%, p = 0.004).

Conclusions

Proton radiotherapy could deliver a higher radiation dose than photon radiotherapy without increasing the risk of RILD and result in a better overall survival rate for those diagnosed with HCC and treated with radiotherapy with curative intent.

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Saini G, Shukla R, Sood KS, Shukla SK, Chandra R. Role of Proton Beam Therapy in Current Day Radiation Oncology Practice. ASIAN JOURNAL OF ONCOLOGY 2020. [DOI: 10.1055/s-0040-1713703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open

Chun SY, Nam KS, Lee KS. Proton Beam Induces P53-mediated Cell Cycle Arrest in HepG2 Hepatocellular Carcinoma Cells. BIOTECHNOL BIOPROC E 2020. [DOI: 10.1007/s12257-019-0390-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]

Comparison of clinical outcomes between passive scattering versus pencil-beam scanning proton beam therapy for hepatocellular carcinoma. Radiother Oncol 2020;146:187-193. [PMID: 32179362 DOI: 10.1016/j.radonc.2020.02.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Revised: 01/22/2020] [Accepted: 02/24/2020] [Indexed: 02/07/2023]

Takahashi H, Sekino Y, Mori K, Okumura T, Nasu K, Fukuda K, Masuoka S, Iizumi T, Hasegawa N, Sakurai H, Minami M. Indicator for local recurrence of hepatocellular carcinoma after proton beam therapy: analysis of attenuation difference between the irradiated tumor and liver parenchyma on contrast enhancement CT. Br J Radiol 2019;93:20190375. [PMID: 31670572 DOI: 10.1259/bjr.20190375] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open

Yuan TZ, Zhan ZJ, Qian CN. New frontiers in proton therapy: applications in cancers. Cancer Commun (Lond) 2019;39:61. [PMID: 31640788 PMCID: PMC6805548 DOI: 10.1186/s40880-019-0407-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 10/11/2019] [Indexed: 12/11/2022] Open

Decreased IL-6 induces sensitivity of hepatocellular carcinoma cells to sorafenib. Pathol Res Pract 2019;215:152565. [DOI: 10.1016/j.prp.2019.152565] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 07/09/2019] [Accepted: 07/24/2019] [Indexed: 02/06/2023]

Angiographic Findings in Patients with Hepatocellular Carcinoma Previously Treated Using Proton Beam Therapy. JOURNAL OF ONCOLOGY 2019;2019:3580379. [PMID: 31354819 PMCID: PMC6637669 DOI: 10.1155/2019/3580379] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 06/08/2019] [Accepted: 06/18/2019] [Indexed: 01/26/2023]

Abstract

Given the growing interest in using proton beam therapy (PBT) for hepatocellular carcinoma (HCC), it is possible that transarterial chemoembolization (TACE) could be used for selected patients who have previously undergone PBT. However, these cases can be technically challenging to treat and require appropriate preparation. Thus, we aimed to identify angiographic findings in this setting. We retrospectively identified 31 patients (28 men and 3 women, mean age: 69 years, range: 43–84 years) who underwent hepatic angiography plus TACE or transarterial infusion chemotherapy (TAI) for HCC that recurred after PBT (July 2007 to June 2018). We discovered four angiographic findings, which we speculate were related to the previous PBT. 18 patients experienced recurrence in the irradiated field, and 13 patients experienced recurrence outside the irradiated field. 29 patients underwent TACE and only 2 patients underwent TAI. The mean number of previous PBT treatments was 1.3 ± 0.6 (range: 1–4). The median interval from the earliest PBT treatment to hepatic angiography was 559 days (range: 34–5,383 days), and the median interval from the latest PBT treatment to hepatic angiography was 464 days (range: 34–5,383 days). Abnormal staining of the irradiated liver parenchyma was observed in 22 patients, which obscured the angiographic tumor staining in 4 patients. Development of a tortuous tumor feeder vessel was observed in 13 patients. Development of an extrahepatic collateral pathway was observed in 7 patients. Development of an arterioportal or arteriovenous shunt was observed in 4 patients. Based on these findings, we conclude that PBT was associated with various angiographic findings during subsequent transarterial chemotherapy for recurrent HCC, and familiarity with these findings will be important in developing appropriate treatment plans.

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Chen CP. Role of Radiotherapy in the Treatment of Hepatocellular Carcinoma. J Clin Transl Hepatol 2019;7:183-190. [PMID: 31293919 PMCID: PMC6609847 DOI: 10.14218/jcth.2018.00060] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 04/27/2019] [Accepted: 05/08/2019] [Indexed: 02/06/2023] Open

Choi C, Son A, Lee GH, Shin SW, Park S, Ahn SH, Chung Y, Yu JI, Park HC. Targeting DNA-dependent protein kinase sensitizes hepatocellular carcinoma cells to proton beam irradiation through apoptosis induction. PLoS One 2019;14:e0218049. [PMID: 31194786 PMCID: PMC6563991 DOI: 10.1371/journal.pone.0218049] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022] Open

Choi C, Yoo GS, Cho WK, Park HC. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma. World J Gastroenterol 2019;25:2416-2429. [PMID: 31171886 PMCID: PMC6543238 DOI: 10.3748/wjg.v25.i20.2416] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/12/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open