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Portik D, Lacombe D, Faivre-Finn C, Achard V, Andratschke N, Correia D, Spalek M, Guckenberger M, Ost P, Ehret F. The 2024 State of Science report from the European Organisation for Research and Treatment of Cancer's Radiation Oncology Scientific Council. Eur J Cancer 2025; 220:115334. [PMID: 40127505 DOI: 10.1016/j.ejca.2025.115334] [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: 02/25/2025] [Accepted: 02/27/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Radiotherapy (RT) is a central pillar of a multimodal cancer treatment approach. The ongoing advances in the fields of RT, imaging technologies, cancer biology, and others yield the potential to refine the use of RT. The European Organisation for Research and Treatment of Cancer (EORTC) hosted a dedicated workshop to identify and prioritize key research questions and to define future RT-based treatment strategies to improve the survival and quality of life of cancer patients. METHODS An initial call for relevant RT research topics led to the formation of workgroups to develop these into new clinical research proposals and projects. The EORTC Radiation Oncology Scientific Council (ROSC) State of Science workshop was held in Brussels, Belgium, in February 2024, bringing together EORTC members and international stakeholders to connect and work on the proposals. RESULTS Four topics of interest were identified: I) De-escalation of RT, minimizing toxicity while maintaining patients' quality of life, II) Technology-driven RT utilizing advances in treatment techniques, such as spatially fractionated RT to improve outcomes in patients with bulky disease and localized high tumor burden, III) Biology-driven RT, integrating the rapid advances in cancer biology and functional imaging to guide and personalize RT, and IV) New indications adding value and expanding the use of RT. CONCLUSION The EORTC ROSC State of Science workshop prioritized clinical questions to be addressed in prospective clinical research projects to advance RT care and improve patient outcomes.
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Affiliation(s)
- Daniel Portik
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium; Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands.
| | - Denis Lacombe
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium
| | - Corinne Faivre-Finn
- Department of Clinical Oncology, The Christie Hospital NHS Foundation Trust, University of Manchester, Manchester, United Kingdom
| | - Vérane Achard
- Department of Radiotherapy, Institut Bergonié, Bordeaux, France and University of Geneva, Geneva, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Dora Correia
- Department of Radiation Oncology, Cantonal Hospital Aarau, Aarau, Switzerland
| | - Mateusz Spalek
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Piet Ost
- Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Iridium Network, Radiation Oncology, Wilrijk, Belgium
| | - Felix Ehret
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité - Universitätsmedizin Berlin, Germany
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Kirichenko AV, Lee D, Wagner P, Oh S, Lee H, Pavord D, Shamsesfandabadi P, Chen A, Machado L, Bunker M, Sanguino A, Shah C, Uemura T. Image-Guided Stereotactic Body Radiotherapy (SBRT) with Enhanced Visualization of Tumor and Hepatic Parenchyma in Patients with Primary and Metastatic Liver Malignancies. Cancers (Basel) 2025; 17:1088. [PMID: 40227630 PMCID: PMC11988117 DOI: 10.3390/cancers17071088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 04/15/2025] Open
Abstract
GOAL This study evaluates the feasibility and outcome of a personalized MRI-based liver SBRT treatment planning platform with the SPION contrast agent Ferumoxytol® (Sandoz Inc.; Princeton, NJ, USA) to maintain a superior real-time visualization of liver tumors and volumes of functional hepatic parenchyma for radiotherapy planning throughout multi-fractionated liver SBRT with online plan adaptations on an Elekta Unity 1.5 T MR-Linac (Elekta; Stockholm, Sweden). MATERIALS AND METHODS Patients underwent SPION-enhanced MRI on the Elekta Unity MR-Linac for improved tumor and functional hepatic parenchyma visualization. An automated contouring algorithm was applied for the delineation and subsequent guided avoidance of functional liver parenchyma volumes (FLVs) on the SPION-enhanced MR-Linac. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were assessed with at least 6-month radiographic follow-up. Pre- and post-transplant outcomes were analyzed in the subset of patients with HCC and hepatic cirrhosis who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease (MELD-Na) was used to score hepatic function before and after SBRT. RESULTS With a median follow-up of 23 months (range: 3-40 months), 23 HCC patients (26 lesions treated) and 9 patients (14 lesions treated) with hepatic metastases received SBRT (mean dose: 48 Gy, range: 36-54 Gy) in 1-5 fractions. Nearly all patients in this study had pe-existing liver conditions, including hepatic cirrhosis (23), prior TACE (7), prior SBRT (18), or history of hepatic resection (2). Compared to the non-contrast images, SPIONs improved tumor visibility on post-SPION images on the background of negatively enhancing functionally active hepatic parenchyma. Prolonged SPION-contrast retention within hepatic parenchyma enabled per-fraction treatment adaptation throughout the entire multi-fraction treatment course. FLV loss (53%, p < 0.0001) was observed in cirrhotic patients, but functional and anatomic liver volumes remained consistent in non-cirrhotic patients. Mean dose to FLV was maintained within the liver threshold tolerance to radiation in all patients after the optimization of Step-and-Shoot Intensity-Modulated Radiotherapy (SS-IMRT) on the SPION-enhanced MRI-Linac. No radiation-induced liver disease was observed within 6 months post-SBRT, and the MELD-Na score in cirrhotic patients was not significantly elevated at 3-month intervals after SBRT completion. CONCLUSIONS SPION Ferumoxytol® administered intravenously as an alternative MRI contrast agent on the day of SBRT planning produces a long-lasting contrast effect between tumors and functional hepatic parenchyma for precision targeting and guided avoidance during the entire course of liver SBRT, enabling fast and accurate online plan adaptation on the 1.5 T Elekta Unity MR-Linac. This approach demonstrates a safe and effective bridging therapy for patients with hepatic cirrhosis, leading to low toxicity and favorable transplant outcomes.
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Affiliation(s)
- Alexander V. Kirichenko
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Danny Lee
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Patrick Wagner
- Division of Surgical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA;
| | - Seungjong Oh
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Hannah Lee
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Daniel Pavord
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Parisa Shamsesfandabadi
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Allen Chen
- Division of Abdominal Transplantation, Allegheny General Hospital, Pittsburgh, PA 15212, USA; (A.C.); (L.M.); (T.U.)
| | - Lorenzo Machado
- Division of Abdominal Transplantation, Allegheny General Hospital, Pittsburgh, PA 15212, USA; (A.C.); (L.M.); (T.U.)
| | - Mark Bunker
- Department of Clinical Pathology, Allegheny General Hospital, Pittsburgh, PA 15212, USA; (M.B.); (A.S.)
| | - Angela Sanguino
- Department of Clinical Pathology, Allegheny General Hospital, Pittsburgh, PA 15212, USA; (M.B.); (A.S.)
| | - Chirag Shah
- Division of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA; (D.L.); (S.O.); (H.L.); (D.P.); (P.S.); (C.S.)
| | - Tadahiro Uemura
- Division of Abdominal Transplantation, Allegheny General Hospital, Pittsburgh, PA 15212, USA; (A.C.); (L.M.); (T.U.)
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Ma ZH, Lin XL, Liu FH, Zhang JL, Yan ML, Song XC, Guo L, Xue J, Lu CD, Shi J, Meng Y, Cheng SQ, Guo WX. Radiofrequency ablation versus stereotactic body radiotherapy for recurrent hepatocellular carcinoma: a multicenter, propensity score matching analysis. BMC Cancer 2025; 25:424. [PMID: 40057688 PMCID: PMC11889815 DOI: 10.1186/s12885-025-13800-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 02/24/2025] [Indexed: 05/13/2025] Open
Abstract
PURPOSE This study aimed at analyzing and comparing the clinical efficacy and prognosis of stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) in the treatment of recurrent hepatocellular carcinoma (RHCC). METHODS Clinicopathological data of RHCC patients who underwent RFA or SBRT as treatment from three medical centers were retrospectively reviewed. The survival outcomes of patients who underwent SBRT were compared with those who underwent RFA. Using the Kaplan-Meier method, survival curves for the two groups of patients were generated, and the log-rank test was used to compare survival differences. Propensity score matching (PSM) analysis was used to match patients of the SBRT and RFA groups in a 1:1 ratio. RESULTS The SBRT group had a significantly better overall survival (OS) than the RFA group and no statistical differences were found in disease-free survival (DFS) in the two groups before and after PSM. After PSM, subgroup analysis demonstrated that, compared with the RFA group, the SBRT group had a significantly better OS in terms of tumor location in the subphrenic or subcapsular area, tumor size > 2.5 cm, and tumor proximity to major vessels ≤ 1 cm. CONCLUSIONS SBRT appears to be an effective priority to RFA for RHCC patients especially when RFA is not feasible due to tumor location, size, and proximity to major vessels.
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Affiliation(s)
- Zi-Hui Ma
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Xiao-Lu Lin
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Feng-Hua Liu
- Department of Radiation Oncology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Jing-Lei Zhang
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Mao-Lin Yan
- Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China
| | - Xing-Chao Song
- Department of Hepatobiliary and Pancreatic Surgery, Xuzhou Municipal First People's Hospital, Xuzhou, China
| | - Lei Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Jie Xue
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Chong-De Lu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China
| | - Yan Meng
- Department of Radiation Oncology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
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Diamond BH, Banson K, Ayash J, Lee P, Shukla UC, Jones G, Rava P, Fitzgerald TJ, Sioshansi S. Outcomes After Stereotactic Body Radiation for Hepatocellular Carcinoma in Patients With Child-Pugh A Versus Child-Pugh B/C Cirrhosis. Adv Radiat Oncol 2024; 9:101631. [PMID: 39559260 PMCID: PMC11570226 DOI: 10.1016/j.adro.2024.101631] [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: 02/13/2024] [Accepted: 07/02/2024] [Indexed: 11/20/2024] Open
Abstract
Purpose For patients with hepatocellular carcinoma (HCC), stereotactic body radiation therapy (SBRT) has emerged as a locoregional treatment. Our purpose was to report outcomes in patients with HCC with Child-Pugh A (CP A) versus Child-Pugh B or C (CP B/C) liver dysfunction treated with SBRT. Methods and Materials A retrospective analysis of 80 patients with HCC, with a total of 94 tumors treated with SBRT, was conducted at a single institution. Outcomes were compared between patients with CP A (n = 51) and CP B/C (n = 29) liver dysfunction. Outcomes of interest included local control, overall survival (OS), and toxicity. Results Median tumor size was 3.2 cm. There were 59 tumors included in the CP A cohort and 35 tumors in the CP B/C cohort. Median radiation dose was 50 Gy in 5 fractions for the CP A cohort and 40 Gy in 5 fractions for the CP B/C cohort. The rates of pathologic complete response were similar between the 2 groups at 63% for the CP A group and 61% for the CP B/C group. The estimated 1-year local control rates were similar between the 2 groups at 93% for the CP A group and 91% for the CP B/C group (P = .59). The 1-year OS for the CP A group was 85%, whereas the 1-year OS for the CP B/C group was 61% (P = .19). There was a 5.9% rate of grade 3+ toxicity in the CP A group and a 20.7% rate of grade 3+ toxicity in the CPB/C group. Conclusions Our findings suggest that SBRT is feasible and effective in patients with both CP A and CP B/C liver dysfunction with similar rates of local control and pathologic complete response despite lower radiation doses in the CP B/C cohort. In patients with more advanced CP B/C cirrhosis, toxicities were higher and must be weighed against possible treatment benefits. Further studies characterizing the optimal role of SBRT in patients with advanced cirrhosis are warranted.
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Affiliation(s)
- Brett H. Diamond
- Department of Radiation Oncology, Tufts Medical Center, Boston, Massachusetts
| | - Kara Banson
- Department of Radiation Oncology, New York University, New York, New York
| | - Jonathan Ayash
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Peter Lee
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | | | - Gavin Jones
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Paul Rava
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Thomas J. Fitzgerald
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
| | - Shirin Sioshansi
- Department of Radiation Oncology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
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Brewster F, Middleton Z, McWilliam A, Brocklehurst A, Radhakrishna G, Chuter R. Feasibility of using contrast-free quantitative magnetic resonance imaging for liver sparing stereotactic ablative body radiotherapy. Clin Transl Radiat Oncol 2024; 49:100859. [PMID: 39376618 PMCID: PMC11456905 DOI: 10.1016/j.ctro.2024.100859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 10/09/2024] Open
Abstract
Background and purpose Tumours in the liver often develop on a background of liver cirrhosis and impaired liver function. As a result, radiotherapy treatments are limited by radiation-induced liver disease, parameterised by the liver mean dose (LMD). Liver function is highly heterogeneous, especially in liver cancer, but the use of LMD does not take this into account. One possible way to improve liver treatments is to use quantitative imaging techniques to assess liver health and prioritise the sparing of healthy liver tissue. Materials and methods Anatomical T2 and quantitative iron-corrected T1 (cT1) images were made available for 10 patients with liver metastases. Functional liver volumes were automatically segmented on the quantitative images using a threshold. Liver stereotactic ablative body radiotherapy (SABR) plans were made using a departmental protocol. Liver-sparing plans were then made by reducing the dose to the functional sub-volume. Results The sparing plans achieved a statistically significant ( p = 0.002 ) reduction in the functional liver mean dose, with a mean reduction of 1.4 Gy. The LMD was also significantly different ( p = 0.002 ) but had a smaller magnitude with a mean reduction of 0.7 Gy. There were some differences in the planning target volume D99% ( p = 0.04 ) but the sparing plans remained within the optimal tolerance and the D95% was not significantly different ( p = 0.2 ). Conclusions This study has, for the first time, demonstrated the use of cT1 maps in radiotherapy showing significant reductions in dose to the healthy liver. Further work is needed to validate this in liver cancer patients, who would likely benefit most.
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Affiliation(s)
- Frank Brewster
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Alan McWilliam
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
| | - Andrew Brocklehurst
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Ganesh Radhakrishna
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | - Robert Chuter
- Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK
- Department of Radiotherapy Related Research, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
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Yang Z, Liu S, Hu L, Chen J, Wang J, Pan Y, Xu L, Liu M, Chen M, Xi M, Zhang Y. Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm. JHEP Rep 2024; 6:101151. [PMID: 39308987 PMCID: PMC11416668 DOI: 10.1016/j.jhepr.2024.101151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 09/25/2024] Open
Abstract
Background & Aims Radiation therapy has been refined with increasing evidence of the benefits of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤5.0 cm. Methods Patients with a single HCC lesion ≤5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate, progression-free survival, overall survival, adverse events and subsequent treatments after recurrence were analyzed. Results A total of 288 patients receiving RFA (n = 166) or SBRT (n = 122) were enrolled. The baseline characteristics between the two groups were comparable. The cumulative local recurrence rate in the SBRT group was significantly lower than that in the RFA group (hazard ratio [HR] 0.30, 95% CI 0.16-0.57, p <0.001), especially for patients with tumours >2.0 cm (HR 0.20, 95% CI 0.08-0.50, p <0.001) or adjacent to major vessels (HR 0.29, 95% CI 0.13-0.66, p <0.001). Cumulative distant recurrence rate, progression-free survival and overall survival were not significantly different between the two groups (all p >0.050). Adverse events were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and total bilirubin increases. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (p <0.001). Conclusions Both RFA and SBRT were effective and safe for HCC with a single lesion ≤5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumours >2.0 cm or adjacent to major vessels. Impact and implications Stereotactic body radiation therapy (SBRT) may be used as an alternative treatment to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumours >3 cm and those with 1 to 3 tumours. This study focused on HCC patients with a specific tumour burden, namely a single lesion ≤5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumours >2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.
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Affiliation(s)
- Zhoutian Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Shiliang Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Li Hu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Jinbin Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Juncheng Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Yangxun Pan
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Li Xu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Mengzhong Liu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Minshan Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Mian Xi
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
| | - Yaojun Zhang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China
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Shen J, Zhong N, Chen Z, Ma D, Lin J. The impacts of physical factors on huge hepatocellular carcinoma treated by transarterial chemoembolization combined with radiotherapy. Future Oncol 2024:1-11. [PMID: 39263953 DOI: 10.1080/14796694.2024.2395801] [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: 05/23/2024] [Accepted: 08/20/2024] [Indexed: 09/13/2024] Open
Abstract
Aims: To assess the influence of various physical factors on the outcome of transarterial chemoembolization combined with γ-ray hypofractionated radiation therapy (TACE-γHRT) for unresectable huge (≥10 cm) hepatocellular carcinoma (UH-HCC) patients.Materials & methods: A total of 162 UH-HCC patients with different tumor locations treated with TACE-γHRT and a retrospective analysis was conducted to evaluate the impacts of selected physical parameters on clinical outcomes.Results: The selected physical factors influenced the clinical outcomes significantly. No adverse events exceeding grade 3 were observed in the enrolled patients.Conclusion: Higher P70 and marginal dose, smaller tumor size and tumor location of neither skin nor gastrointestinal tracts involved were independent predictors for better overall survival and progression free survival.
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Affiliation(s)
- Juanjuan Shen
- Department of Tumor Radiotherapy, 900th Hospital of PLA, Fuzhou, China
| | - Nanbao Zhong
- Department of Tumor Radiotherapy, 900th Hospital of PLA, Fuzhou, China
| | - Zhonghua Chen
- Department of Tumor Radiotherapy, 900th Hospital of PLA, Fuzhou, China
| | - Danyu Ma
- Department of Tumor Radiotherapy, 900th Hospital of PLA, Fuzhou, China
| | - Jianhai Lin
- Department of Tumor Radiotherapy, 900th Hospital of PLA, Fuzhou, China
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Yoshino Y, Suzuki G, Shiomi H, Kimoto T, Seri S, Yamazaki H, Yamada K. Albumin-bilirubin score is a useful predictor of worsening liver reserve after stereotactic body radiation therapy in elderly Japanese patients with hepatocellular carcinoma. JOURNAL OF RADIATION RESEARCH 2024; 65:244-250. [PMID: 38415344 PMCID: PMC10959440 DOI: 10.1093/jrr/rrae006] [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: 11/25/2023] [Revised: 01/09/2024] [Indexed: 02/29/2024]
Abstract
The prognosis of patients with hepatocellular carcinoma (HCC) is closely related to their liver reserves. The Child-Pugh (CP) score has traditionally been used to evaluate this reserve, with CP Grade B (CP score ≥ 7) associated with a higher risk of radiation-induced liver disease after stereotactic body radiation therapy (SBRT). However, the CP score has limitations, as it does not accurately assess liver reserve capacity. The albumin-bilirubin (ALBI) score has been introduced as a meticulous indicator of liver reserve for the treatment of HCC. We retrospectively evaluated the role of the ALBI score in estimating the worsening liver reserve in 42 patients with HCC treated with SBRT using CyberKnife between 2015 and 2023. The median biologically effective dose (α/β = 10 Gy) was 100 Gy. For a median follow-up duration of 17.4 months, the 1-year overall survival (OS), local control (LC) and progression-free survival (PFS) rates were 100, 98 and 62%, respectively. Worsening liver reserve was defined as an increase in the modified ALBI grade or CP score within 1 year after SBRT. Univariate and multivariate analyses showed that the baseline ALBI score (≥-2.7 vs <-2.7) was the only significantly different predictor of worsening liver reserve. The OS and LC rates after SBRT for HCC were satisfactory. However, the PFS was poor, and recurrent HCC will require additional treatment. It is clinically important to predict the liver reserve capacity after SBRT, and the baseline ALBI score is a useful predictor.
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Affiliation(s)
- Yuki Yoshino
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Gen Suzuki
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Hiroya Shiomi
- Department of Radiation Oncology, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
- Department of Radiology, Soseikai CyberKnife Center, Fushimi-ku, Kyoto 612-8248, Japan
| | - Takuya Kimoto
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Sho Seri
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Hideya Yamazaki
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
| | - Kei Yamada
- Department of Radiology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
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9
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Podesta C, Kayani M, Goody R, Samson A. Combination treatment of HCC with SBRT and immune checkpoint inhibition. Crit Rev Oncol Hematol 2023; 192:104191. [PMID: 37865277 DOI: 10.1016/j.critrevonc.2023.104191] [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: 05/21/2023] [Revised: 09/10/2023] [Accepted: 10/17/2023] [Indexed: 10/23/2023] Open
Abstract
The treatment of unresectable or metastatic HCC has been significantly advanced in recent years by developments in both radiotherapy and systemic cancer therapies. Independently, both Stereotactic Ablative Body Radiotherapy (SBRT) and Immune Checkpoint Inhibitors (ICIs) are licensed for the treatment of these tumours. Building on the successes seen in other solid tumours, there is significant interest in exploring combination treatments. In this review article we briefly present the evidence base for the use of these treatments in patients with HCC. With reference to our current understanding of the immuno-oncology and radiobiology of HCCs, we demonstrate why combining these two modalities is of interest. Finally, we discuss the clinical trials that are currently underway or planned and the direction that future research may take.
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Affiliation(s)
- Christine Podesta
- Leeds Cancer Centre, St James University Hospital, Beckett Street, Leeds, UK
| | - Mahaz Kayani
- Leeds Cancer Centre, St James University Hospital, Beckett Street, Leeds, UK.
| | - Rebecca Goody
- Leeds Cancer Centre, St James University Hospital, Beckett Street, Leeds, UK
| | - Adel Samson
- Leeds Cancer Centre, St James University Hospital, Beckett Street, Leeds, UK
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10
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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11
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Birgin E, Hetjens S, Tam M, Correa-Gallego C, Rahbari NN. Stereotactic Body Radiation Therapy versus Surgical Resection for Stage I/II Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15082330. [PMID: 37190258 DOI: 10.3390/cancers15082330] [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: 02/15/2023] [Revised: 04/04/2023] [Accepted: 04/14/2023] [Indexed: 05/17/2023] Open
Abstract
SBRT is an emerging locoregional treatment modality for hepatocellular carcinoma (HCC). Although local tumor control rates seem encouraging, large-scale survival data comparing SBRT to surgical resection are lacking. We identified patients with stage I/II HCC from the National Cancer Database amenable for potential surgical resection. Patients undergoing hepatectomy were matched by propensity score (1:2) with patients who underwent SBRT as primary treatment. A total of 3787 (91%) and 366 (9%) patients underwent surgical resection or SBRT between 2004 and 2015, respectively. After propensity matching, the 5-year overall survival was 24% (95% CI 19-30%) in the SBRT group versus 48% (95% CI 43-53%) in the surgery group (p < 0.001). The association of surgery with overall survival was consistent in all subgroups. In patients treated with SBRT, a biologic effective dose (BED) of ≥100 Gy (31%, 95% CI 22%-40%) compared with BED < 100 Gy (13%, 95% CI 8-22%) was associated with a higher 5-year overall survival rate (hazard ratio of mortality of 0.58, 95% CI 0.43-0.77; p < 0.001). Surgical resection may be associated with prolonged overall survival compared with SBRT in patients with stage I/II HCC.
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Affiliation(s)
- Emrullah Birgin
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
| | - Svetlana Hetjens
- Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
| | - Moses Tam
- Department of Radiation Oncology, NYU Grossman School of Medicine, New York, NY 10016, USA
| | | | - Nuh N Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
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12
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Yano S, Kimura T, Kawaoka T, Kinami T, Yamasaki S, Johira Y, Kosaka M, Amioka K, Naruto K, Ando Y, Yamaoka K, Fujii Y, Uchikawa S, Fujino H, Ono A, Nakahara T, Murakami E, Okamoto W, Yamauchi M, Imamura M, Hirokawa J, Nagata Y, Aikata H, Oka S. Effectiveness of Repeated Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma-Consideration of the Locations of Target Lesions. Cancers (Basel) 2023; 15:cancers15030846. [PMID: 36765804 PMCID: PMC9913412 DOI: 10.3390/cancers15030846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/24/2023] [Accepted: 01/27/2023] [Indexed: 02/02/2023] Open
Abstract
The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.
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Affiliation(s)
- Shigeki Yano
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Tomoki Kimura
- Department of Radiation Oncology, Kochi University, Kochi 783-8505, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
- Correspondence: ; Tel.: +81-82-257-5555; Fax: +81-82-257-1728
| | - Takahiro Kinami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Shintaro Yamasaki
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yusuke Johira
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Masanari Kosaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Kei Amioka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Kensuke Naruto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yuwa Ando
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Kenji Yamaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
| | - Junichi Hirokawa
- Department of Radiation Oncology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Yasushi Nagata
- Department of Radiation Oncology, Hiroshima University, Hiroshima 734-8551, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima 734-0004, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
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13
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Tadimalla S, Wang W, Haworth A. Role of Functional MRI in Liver SBRT: Current Use and Future Directions. Cancers (Basel) 2022; 14:cancers14235860. [PMID: 36497342 PMCID: PMC9739660 DOI: 10.3390/cancers14235860] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/23/2022] [Accepted: 11/24/2022] [Indexed: 11/30/2022] Open
Abstract
Stereotactic body radiation therapy (SBRT) is an emerging treatment for liver cancers whereby large doses of radiation can be delivered precisely to target lesions in 3-5 fractions. The target dose is limited by the dose that can be safely delivered to the non-tumour liver, which depends on the baseline liver functional reserve. Current liver SBRT guidelines assume uniform liver function in the non-tumour liver. However, the assumption of uniform liver function is false in liver disease due to the presence of cirrhosis, damage due to previous chemo- or ablative therapies or irradiation, and fatty liver disease. Anatomical information from magnetic resonance imaging (MRI) is increasingly being used for SBRT planning. While its current use is limited to the identification of target location and size, functional MRI techniques also offer the ability to quantify and spatially map liver tissue microstructure and function. This review summarises and discusses the advantages offered by functional MRI methods for SBRT treatment planning and the potential for adaptive SBRT workflows.
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Affiliation(s)
- Sirisha Tadimalla
- Institute of Medical Physics, School of Physics, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia
- Correspondence:
| | - Wei Wang
- Crown Princess Mary Cancer Centre, Sydney West Radiation Oncology Network, Western Sydney Local Health District, Sydney, NSW 2145, Australia
| | - Annette Haworth
- Institute of Medical Physics, School of Physics, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia
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14
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Fu HJ, Chen PY, Yang HY, Tsang YW, Lee CY. Liver-directed stereotactic body radiotherapy can be reliably delivered to selected patients without internal fiducial markers-A case series. J Chin Med Assoc 2022; 85:1028-1032. [PMID: 36000954 DOI: 10.1097/jcma.0000000000000798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Tumor motion and the lack of tissue-tumor contrast have been challenging parts of liver-directed stereotactic body radiotherapy (SBRT). In this study, we investigated the possibility of liver-directed SBRT without internal fiducials using breath hold technique and diaphragm matching technique. One hundred thirty-four volumetric images of 13 consecutive patients with either primary or metastatic liver tumors who underwent expiratory breath hold SBRT were compared and analyzed. Reproducibility of diaphragm position between fractions relative to bone was evaluated on image registration software. At median follow-up time of 13 months, 1-year and 2-year local control rates of index lesions were 90% and 72%, respectively. In comparison to diaphragm matching, a greater margin is required for bone matching technique for that 19 of 67 (28%) of all interfractional SI offsets were more than 6 mm, whereas 6 of 67 (9%) intrafractional SI exceeded 6 mm. Despite the small study size, our study showed that breath hold SBRT without internal hepatic fiducial is a valid approach for selected patients.
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Affiliation(s)
- Hsiao-Ju Fu
- Department of Radiation Therapy and Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC
| | - Po-Yueh Chen
- Department of Internal Medicine, Ditmanson Medication Foundation, Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC
| | - Hsin-Yi Yang
- Clinical Research Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC
| | - Yuk-Wah Tsang
- Department of Radiation Therapy and Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC
| | - Cheng-Yen Lee
- Department of Radiation Therapy and Oncology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, ROC
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15
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Su TH, Hsu SJ, Kao JH. Paradigm shift in the treatment options of hepatocellular carcinoma. Liver Int 2022; 42:2067-2079. [PMID: 34515412 DOI: 10.1111/liv.15052] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is prevalent worldwide with suboptimal therapeutic outcomes. The advancement of therapeutic options and the development of new systemic therapies expand the armamentarium to tackle HCC. Treatment options should be provided based on the hierarchy of efficacy in a multidisciplinary perspective, instead of the traditional stage-guided scheme. In advanced HCC, lenvatinib has a comparable efficacy as sorafenib for the first-line therapy of HCC; while regorafenib, cabozantinib, and ramucirumab have been approved as second-line therapy after the failure of sorafenib. Immune checkpoint inhibitor therapy prolongs response rate and survival and enables long-term cure. Atezolizumab plus bevacizumab is superior to sorafenib as the first-line therapy for advanced HCC. Several emerging regimens by the combination of various systemic therapies are currently under clinical trials. Systemic therapy may be used in the neoadjuvant, adjuvant or even as initial therapy for intermediate-stage HCC. The paradigm shift of HCC treatment will improve patient outcomes.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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16
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Peer review quality assurance in stereotactic body radiotherapy planning: the impact of case volume. JOURNAL OF RADIOTHERAPY IN PRACTICE 2022. [DOI: 10.1017/s1460396922000152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Abstract
Purpose:
Peer review is an essential quality assurance component of radiation therapy planning. A growing body of literature has demonstrated substantial rates of suggested plan changes resulting from peer review. There remains a paucity of data on the impact of peer review rounds for stereotactic body radiation therapy (SBRT). We therefore aim to evaluate the outcomes of peer review in this specific patient cohort.
Methods and materials:
We conducted a retrospective review of all SBRT cases that underwent peer review from July 2015 to June 2018 at a single institution. Weekly peer review rounds are grouped according to cancer subsite and attended by radiation oncologists, medical physicists and medical radiation technologists. We prospectively compiled ‘learning moments’, defined as cases with suggested changes or where an educational discussion occurred beyond routine management, and critical errors, defined as errors which could alter clinical outcomes, recorded prospectively during peer review. Plan changes implemented after peer review were documented.
Results:
Nine hundred thirty-four SBRT cases were included. The most common treatment sites were lung (518, 55%), liver (196, 21%) and spine (119, 13%). Learning moments were identified in 161 cases (17%) and translated into plan changes in 28 cases (3%). Two critical errors (0.2%) were identified: an inadequate planning target volume margin and an incorrect image set used for contouring. There was a statistically significantly higher rate of learning moments for lower-volume SBRT sites (defined as ≤30 cases/year) versus higher-volume SBRT sites (29% vs 16%, respectively; p = 0.001).
Conclusions:
Peer review for SBRT cases revealed a low rate of critical errors, but did result in implemented plan changes in 3% of cases, and either educational discussion or suggestions of plan changes in 17% of cases. All SBRT sites appear to benefit from peer review, though lower-volume sites may require particular attention.
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17
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Allam N, Jeffrey Zabel W, Demidov V, Jones B, Flueraru C, Taylor E, Alex Vitkin I. Longitudinal in-vivo quantification of tumour microvascular heterogeneity by optical coherence angiography in pre-clinical radiation therapy. Sci Rep 2022; 12:6140. [PMID: 35414078 PMCID: PMC9005734 DOI: 10.1038/s41598-022-09625-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/16/2022] [Indexed: 11/25/2022] Open
Abstract
Stereotactic body radiotherapy (SBRT) is an emerging cancer treatment due to its logistical and potential therapeutic benefits as compared to conventional radiotherapy. However, its mechanism of action is yet to be fully understood, likely involving the ablation of tumour microvasculature by higher doses per fraction used in SBRT. In this study, we hypothesized that longitudinal imaging and quantification of the vascular architecture may elucidate the relationship between the microvasculature and tumour response kinetics. Pancreatic human tumour xenografts were thus irradiated with single doses of \documentclass[12pt]{minimal}
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\begin{document}$$30$$\end{document}30 Gy to simulate the first fraction of a SBRT protocol. Tumour microvascular changes were monitored with optical coherence angiography for up to \documentclass[12pt]{minimal}
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\begin{document}$$8$$\end{document}8 weeks following irradiation. The temporal kinetics of two microvascular architectural metrics were studied as a function of time and dose: the diffusion-limited fraction, representing poorly vascularized tissue \documentclass[12pt]{minimal}
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\begin{document}$$>150$$\end{document}>150 μm from the nearest detected vessel, and the vascular distribution convexity index, a measure of vessel aggregation at short distances. These biological metrics allowed for dose dependent temporal evaluation of tissue (re)vascularization and vessel aggregation after radiotherapy, showing promise for determining the SBRT dose–response relationship.
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Affiliation(s)
- Nader Allam
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada.
| | - W Jeffrey Zabel
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada
| | - Valentin Demidov
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada.,Geisel School of Medicine at Dartmouth, 1 Rope Ferry Rd, Hanover, NH, 03755, USA
| | - Blake Jones
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada
| | - Costel Flueraru
- National Research Council Canada, Information Communication Technology, 1200 Montreal Rd, Ottawa, ON, K1A 0R6, Canada
| | - Edward Taylor
- Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.,Department of Radiation Oncology, University of Toronto, 149 College Street, Toronto, ON, M5T 1P5, Canada
| | - I Alex Vitkin
- Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, M5G 1L7, Canada. .,Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. .,Department of Radiation Oncology, University of Toronto, 149 College Street, Toronto, ON, M5T 1P5, Canada.
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18
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Liang Z, Xue C, Chen Q, Li M, Li G, Feng H, Liu Y, Liu X, Ma S. Screening of Prognostic Biomarkers for Stereotactic Body Radiation Therapy in Primary Liver Cancer. Dose Response 2022; 20:15593258221097589. [PMID: 35547468 PMCID: PMC9083052 DOI: 10.1177/15593258221097589] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 04/10/2022] [Indexed: 11/15/2022] Open
Abstract
Objective So far there are still no effective immediate-early markers for assessing the efficacy of Stereotactic Body Radiation Therapy (SBRT). To find effective biomarkers for accurate assessment of the efficacy of SBRT in patients with primary liver cancer, we conducted this study including retrospective part and prospective part. Material and Methods 589 patients with primary liver cancer were included at Ruikang Hospital affiliated to Guangxi Medical University from January 2012 to December 2018. Follow-up was conducted, clinical information and a total of 17 patients with 51 blood samples (before SBRT, before discharge and 2 months after SBRT) were collected. mRNAs profiles on 2 patients with 6 blood samples were detected by high-throughput sequencing, followed by qPCR verification on 15 patients with 45 blood samples. Results The commonly used serum biomarkers such as AFP, CEA, and CA125 shown low prognostic value in distinguishing survival group and death group, indicated by low AUC (less than .7) and Youden indexes (less than .5). Based on high-throughput sequencing of test group and qPCR detection of another verification group, we found 16 up-regulated and 12 downregulated genes after SBRT. Among them, ADIPOR1 and EPB42 showed significantly different between effective and ineffective group after SBRT, ROC suggested that based on the optimal threshold of .5838, ADIPOR1 shown a sensitivity of 100% and a specificity of 83.33% to distinguish effective from ineffective group. And EPB42 had a sensitivity of 75% and a specificity of 100% at the optimal threshold of 1.3817. In addition, GSEA showed that high expression of ADIPOR1 was mainly related to Mismatch repair, Circadian rhythm, Protein processing in endoplasmic reticulum, DNA replication, and Fanconi anemia pathways. Conclusion ADIPOR1 in whole blood is a promising candidate to act as prognostic biomarker for predication of SBRT outcomes in primary liver cancer patients.
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Affiliation(s)
- Zhenzhen Liang
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
- NHC Key Laboratory of Radiobiology (Jilin University), Changchun, Jilin, China
| | - Chang Xue
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qing Chen
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mengke Li
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Guanghui Li
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hao Feng
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yi Liu
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaodong Liu
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
- South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, Zhejiang, China
- Key Laboratory of Watershed Science and Health of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Shumei Ma
- School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, China
- South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, Zhejiang, China
- Key Laboratory of Watershed Science and Health of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, China
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19
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Mendiratta-Lala M, Aslam A, Maturen KE, Westerhoff M, Sun Y, Maurino C, Parikh ND, Sonnenday CJ, Stein EB, Shampain KL, Kaza RK, Cuneo K, Masch W, Do RKG, Lawrence TS, Owen D. LI-RADS Treatment Response Algorithm: Performance and Diagnostic Accuracy With Radiologic-Pathologic Explant Correlation in Patients With SBRT-Treated Hepatocellular Carcinoma. Int J Radiat Oncol Biol Phys 2022; 112:704-714. [PMID: 34644607 PMCID: PMC9400832 DOI: 10.1016/j.ijrobp.2021.10.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard. METHODS AND MATERIALS This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (<100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test. RESULTS A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k = 0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant. CONCLUSIONS LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients.
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Affiliation(s)
| | | | | | - Maria Westerhoff
- Department of Pathology and clinical labs, University of Michigan Health System, NCRC building 35 2800 Plymouth Road Ann Arbor, MI 48109
| | | | | | - Neehar D. Parikh
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine
| | | | | | | | | | - Kyle Cuneo
- Department of Radiation Oncology, University of Michigan School of Medicine
| | | | | | | | - Dawn Owen
- Department of Radiation Oncology, Mayo Clinic Rochester, 200 First St SW, Rochester, MN 55905
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20
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Xiao H, Ni R, Zhi S, Li W, Liu C, Ren G, Teng X, Liu W, Wang W, Zhang Y, Wu H, Lee HFV, Cheung LYA, Chang HCC, Li T, Cai J. A Dual-supervised Deformation Estimation Model (DDEM) for constructing ultra-quality 4D-MRI based on a commercial low-quality 4D-MRI for liver cancer radiation therapy. Med Phys 2022; 49:3159-3170. [PMID: 35171511 DOI: 10.1002/mp.15542] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/09/2022] [Accepted: 02/09/2022] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Most available 4D-MRI techniques are limited by insufficient image quality and long acquisition times or require specially designed sequences or hardware that are not available in the clinic. These limitations have greatly hindered the clinical implementation of 4D-MRI. PURPOSE This study aims to develop a fast ultra-quality (UQ) 4D-MRI reconstruction method using a commercially available 4D-MRI sequence and dual-supervised deformation estimation model (DDEM). METHODS Thirty-nine patients receiving radiotherapy for liver tumors were included. Each patient was scanned using a TWIST-VIBE MRI sequence to acquire 4D-MR images. They also received 3D T1-/T2-weighted MRI scans as prior images and UQ 4D-MRI at any instant was considered a deformation of them. A DDEM was developed to obtain a 4D deformable vector field (DVF) from 4D-MRI data, and the prior images were deformed using this 4D-DVF to generate UQ 4D-MR images. The registration accuracies of the DDEM, VoxelMorph (normalized cross-correlation (NCC) supervised), VoxelMorph (end-to-end point error (EPE) supervised), and the parametric total variation (pTV) algorithm were compared. Tumor motion on UQ 4D-MRI was evaluated quantitatively using region-of-interest (ROI) tracking errors, while image quality was evaluated using the contrast-to-noise ratio (CNR), lung-liver edge sharpness, and perceptual blur metric (PBM). RESULTS The registration accuracy of the DDEM was significantly better than those of VoxelMorph (NCC supervised), VoxelMorph (EPE supervised) and the pTV algorithm (all, p < 0.001), with an inference time of 69.3 ± 5.9 ms. UQ 4D-MRI yielded ROI tracking errors of 0.79 ± 0.65, 0.50 ± 0.55, and 0.51 ± 0.58 mm in the superior-inferior, anterior-posterior, and mid-lateral directions, respectively. From the original 4D-MRI to UQ 4D-MRI, the CNR increased from 7.25 ± 4.89 to 18.86 ± 15.81; the lung-liver edge full-width-at-half-maximum decreased from 8.22 ± 3.17 to 3.65 ± 1.66 mm in the in-plane direction and from 8.79 ± 2.78 to 5.04 ± 1.67 mm in the cross-plane direction, and the PBM decreased from 0.68 ± 0.07 to 0.38 ± 0.01. CONCLUSION This novel DDEM method successfully generated UQ 4D-MR images based on a commercial 4D-MRI sequence. It shows great promise for improving liver tumor motion management during radiation therapy. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Haonan Xiao
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Ruiyan Ni
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Shaohua Zhi
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Wen Li
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Chenyang Liu
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Ge Ren
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Xinzhi Teng
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Weiwei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital & Institute, Beijing, 100000, China
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital & Institute, Beijing, 100000, China
| | - Yibao Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital & Institute, Beijing, 100000, China
| | - Hao Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital & Institute, Beijing, 100000, China
| | - Ho-Fun Victor Lee
- Department of Clinical Oncology, The University of Hong Kong, Hong Kong SAR, 999077, China
| | - Lai-Yin Andy Cheung
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong SAR, 999077, China
| | | | - Tian Li
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
| | - Jing Cai
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China
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21
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Isaac EI, Hall J, Dault JB, Elbich J, McGhee A, Fields EC. Transarterial Chemoembolization with LC Bead LUMI followed by Stereotactic Body Radiation Therapy in Treatment of Hepatocellular Carcinoma. Adv Radiat Oncol 2022; 7:100830. [PMID: 35071833 PMCID: PMC8767242 DOI: 10.1016/j.adro.2021.100830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/05/2021] [Indexed: 11/30/2022] Open
Affiliation(s)
- Evrosina I. Isaac
- Virginia Commonwealth University, School of Medicine, Richmond, Virginia
| | - Jacob Hall
- Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina
| | - Joshua B. Dault
- Department of Radiation Oncology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Jeffrey Elbich
- Department of Radiology, Vascular Interventional Radiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Adrienne McGhee
- Department of Radiology, Vascular Interventional Radiology, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Emma C. Fields
- Department of Radiation Oncology, Virginia Commonwealth University Health System, Richmond, Virginia
- Corresponding author: Emma C. Fields, MD
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22
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Kibe Y, Takeda A, Tsurugai Y, Eriguchi T, Oku Y, Kimura Y, Nakamura N. Feasibility of marker-less stereotactic body radiotherapy for hepatocellular carcinoma. Acta Oncol 2022; 61:104-110. [PMID: 34788194 DOI: 10.1080/0284186x.2021.2001566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The feasibility of marker-less stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) has not yet been established, and, thus, was examined in the present study. MATERIAL AND METHODS We retrospectively investigated patients who received marker-less SBRT for locally untreated HCC tumors between July 2005 and December 2018. Radiotherapy planning CT was performed under fixation with vacuum cushions and abdominal compression. The clinical target volume (CTV) was equivalent to the gross tumor volume (GTV). The internal target volume (ITV) margin to CTV was determined from calculations based on the motion of the diaphragm. The planning target volume (PTV) margin to ITV was 5-6 mm. In the set-up, radiotherapy planning CT and linac-integrated cone-beam CT performed in the same imaging and fixation settings were merged by referring to the anatomical components surrounding target tumors. The primary endpoint was the 3-year cumulative local tumor progression rate. The upper limit of the 95% confidence interval for the 3-year cumulative local tumor progression rate was less than 7.0%, which was interpreted as favorable local control and feasible for marker-less SBRT. Local tumor progression was assessed by mRECIST. RESULTS We reviewed 180 patients treated with 35-40 Gy/5 fractions. The median follow-up time for the local tumor progression of censored tumors was 32.3 months (range, 0.3-104). The 3-year cumulative local tumor progression rate was 3.0% (95% CI, 1.1-6.5%). The 3-year overall survival rate was 71.6% (95% CI, 63.5-78.2%). Regarding acute hematologic toxicities, grade 3 hypoalbuminemia and thrombocytopenia were detected in 1 (0.6%) and 5 (2.9%) patients, respectively. Treatment-related death from SBRT was not observed. SBRT was initiated within 7 days after radiotherapy planning CT for 84% (152/180) of patients. CONCLUSIONS Marker-less SBRT for HCC achieved favorable local control that fulfilled the threshold. This result suggests that marker-less SBRT with appropriate settings is a feasible treatment strategy.
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Affiliation(s)
- Yuichi Kibe
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
- Radiation Oncology Division, St. Marianna University School of Medicine Hospital, Kawasaki, Kanagawa, Japan
| | - Atsuya Takeda
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Yuichiro Tsurugai
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Takahisa Eriguchi
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Yohei Oku
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Yuto Kimura
- Radiation Oncology Center, Ofuna Chuo Hospital, Kamakura, Kanagawa, Japan
| | - Naoki Nakamura
- Radiation Oncology Division, St. Marianna University School of Medicine Hospital, Kawasaki, Kanagawa, Japan
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23
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De la Pinta C. Toward Personalized Medicine in Radiotherapy of Hepatocellular Carcinoma: Emerging Radiomic Biomarker Candidates of Response and Toxicity. OMICS : A JOURNAL OF INTEGRATIVE BIOLOGY 2021; 25:537-544. [PMID: 34448625 DOI: 10.1089/omi.2021.0065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current and upcoming changes in radiology speak of an overarching new vision for personalized medicine. This is particularly evident in the case of radiotherapy of cancers, and of liver cancer in particular. The development of modern radiotherapy with stereotactic body radiotherapy allows targeted treatments to be delivered to the tumor site, limiting the dose to surrounding healthy organs, thus becoming a new therapeutic alternative for hepatocellular carcinoma and other liver tumors. However, not all patients have the same response to radiotherapy or display the same side-effect profile. Biomarkers of response and toxicity in liver radiotherapy would facilitate the vision and practice of personalized medicine. This expert review examines the available molecular, radiomic, and radiogenomic biomarker candidates for acute liver toxicity with potential use for prediction of radiotherapy-induced liver toxicity. To this end, I highlight for oncologists and life scientists that radiomics allows diagnostic images to be analyzed using computer algorithms to extract information imperceptible to the human eye and of relevance to forecasting clinical outcomes. This article underscores particularly (1) the microRNA-based biomarker candidates as among the most promising predictors of radiation-induced liver toxicity and (2) the texture features in radiomic analyses for response prediction. Radiotherapy of hepatocellular carcinoma is edging toward personalized medicine with emerging radiomic biomarker candidates. Future large-scale biomarker studies are called for to enable personalized medicine in liver cancers.
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Affiliation(s)
- Carolina De la Pinta
- Radiation Oncology Department, Ramon y Cajal University Hospital, IRYCIS, Madrid, Spain
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24
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Rim CH. Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2021; 21:113-123. [PMID: 37383087 PMCID: PMC10035685 DOI: 10.17998/jlc.2021.05.26] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/25/2021] [Accepted: 06/01/2021] [Indexed: 06/30/2023]
Abstract
There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.
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Affiliation(s)
- Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Ansan, Korea
- Korea University Medical College, Seoul, Korea
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25
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Shanker MD, Moodaley P, Soon W, Liu HY, Lee YY, Pryor DI. Stereotactic ablative radiotherapy for hepatocellular carcinoma: A systematic review and meta-analysis of local control, survival and toxicity outcomes. J Med Imaging Radiat Oncol 2021; 65:956-968. [PMID: 34396706 DOI: 10.1111/1754-9485.13309] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/26/2021] [Indexed: 12/13/2022]
Abstract
There is a growing body of literature supporting the use of stereotactic ablative body radiotherapy (SABR) in the management of primary hepatocellular carcinoma (HCC). This systematic review and meta-analysis of the current published evidence for SABR for HCC assessed the impact of treatment dose, fractionation and tumour size on the outcomes of local control (LC), overall survival (OS) and toxicity. A systematic search was independently performed by two authors for articles published in peer-reviewed journals between January 2005 and December 2019. A DerSimonian and Laird random effects model was used to assess pooled results. A multivariate meta-regression analysis incorporated the effect of explanatory variables (radiation dose in EQD2[10], fractionation and tumour size) on outcomes of OS, LC and toxicity. Forty-nine cohorts involving 2846 HCC patients with 3088 lesions treated with SABR were included. Pooled 1-, 2- and 3-year LC rates were 91.1% (95% confidence interval [CI] 88.3-93.2), 86.7% (95% CI 82.7-89.8) and 84.2% (95% CI 77.9-88.9) respectively. Pooled 1-, 2- and 3-year OS rates were 78.4% (95% CI 73.4-82.6), 61.3% (55.2-66.9) and 48.3% (95% CI 39.0-57). Population-weighted median grade 3 toxicity rates were 6.5% (IQR 3.2-16) and mean grade 4/5 rates were 1.4% (IQR 0-2.1). Within EQD2[10] ranges of 40 to 83.33 Gy corresponding to common dose-fractionation regimens of 30-50 Gy in 5 fractions, there was a multivariate association between superior LC and OS with increasing EQD2[10] , with a proportionately smaller increase in grade 3 toxicity and no association with grade 4/5 toxicity. Stereotactic ablative body radiotherapy is a viable treatment option for HCC with high LC rates and low rates of reported grade 3/4 toxicity. Increasing EQD2[10] was associated with improvements in LC and OS with a comparatively smaller increase in toxicity. Prospective randomised trials are warranted to define optimal patient selection and dose-fractionation regimens.
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Affiliation(s)
- Mihir D Shanker
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Pereshin Moodaley
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Wei Soon
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Howard Y Liu
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Yoo Young Lee
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - David I Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
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Heller M, Parikh ND, Fidelman N, Owen D. Frontiers of therapy for hepatocellular carcinoma. Abdom Radiol (NY) 2021; 46:3648-3659. [PMID: 33837453 DOI: 10.1007/s00261-021-03065-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 12/30/2022]
Abstract
The incidence of hepatocellular carcinoma continues to increase worldwide. Fortunately, there have been notable recent advances in locoregional and systemic therapy. In this current review, we will highlight these new developments and future directions of hepatocellular carcinoma treatment and address the importance of a multidisciplinary approach to treatment.
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27
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The effects of stereotactic body radiotherapy on peripheral natural killer and CD3 +CD56 + NKT-like cells in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2021; 20:240-250. [PMID: 33454220 DOI: 10.1016/j.hbpd.2020.12.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 12/15/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. METHODS Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. RESULTS The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. CONCLUSIONS SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.
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28
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Chen LC, Lin HY, Hung SK, Chiou WY, Lee MS. Role of modern radiotherapy in managing patients with hepatocellular carcinoma. World J Gastroenterol 2021; 27:2434-2457. [PMID: 34092968 PMCID: PMC8160620 DOI: 10.3748/wjg.v27.i20.2434] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/16/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Several treatment options are available for managing HCC patients, classified roughly as local, local-regional, and systemic therapies. The high post-monotherapy recurrence rate of HCC urges the need for the use of combined modalities to increase tumor control and patient survival. Different international guidelines offer treatment recommendations based on different points of view and classification systems. Radiotherapy (RT) is a well-known local-regional treatment modality for managing many types of cancers, including HCC. However, only some of these treatment guidelines include RT, and the role of combined modalities is rarely mentioned. Hence, the present study reviewed clinical evidence for the use of different combined modalities in managing HCC, focusing on modern RT's role. Modern RT has an increased utility in managing HCC patients, mainly due to two driving forces. First, technological advancement (e.g., stereotactic body radiotherapy and advanced proton-beam therapy) enables precise delivery of radiation to increase tumor control and reduce side effects in the surrounding normal tissue. Second, the boom in developing target therapies and checkpoint-blockade immunotherapy prolongs overall survival in HCC patients, re-emphasizing the importance of local tumor control. Remarkably, RT combines with systemic therapies to generate the systemic therapy augmented by radiotherapy effect, a benefit now being actively investigated.
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Affiliation(s)
- Liang-Cheng Chen
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
| | - Hon-Yi Lin
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
- Institute of Molecular Biology, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan
| | - Shih-Kai Hung
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Wen-Yen Chiou
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
| | - Moon-Sing Lee
- Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Dalin, Chia-Yi 62247, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 970, Taiwan
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Lee YYD, Nguyen DT, Moodie T, O'Brien R, McMaster A, Hickey A, Pritchard N, Poulsen P, Tabaksblat EM, Weber B, Worm E, Pryor D, Chu J, Hardcastle N, Booth J, Gebski V, Wang T, Keall P. Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring. BMC Cancer 2021; 21:494. [PMID: 33941111 PMCID: PMC8091536 DOI: 10.1186/s12885-021-08184-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 04/13/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .
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Affiliation(s)
- Yoo Young Dominique Lee
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
- The University of Sydney, Sydney, NSW, Australia.
| | - Doan Trang Nguyen
- The University of Sydney, Sydney, NSW, Australia
- School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, Australia
- ACRF Image X Institute, Sydney, NSW, Australia
| | - Trevor Moodie
- Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia
| | - Ricky O'Brien
- ACRF Image X Institute, Sydney, NSW, Australia
- Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Anne McMaster
- Department of Radiation Oncology, Liverpool-Macarthur Cancer Therapy Centre, Sydney, NSW, Australia
| | - Andrew Hickey
- Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia
| | - Nicole Pritchard
- Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia
- Gamma Gurus Pty Ltd, Sydney, NSW, Australia
| | - Per Poulsen
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Britta Weber
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Esben Worm
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - David Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Julie Chu
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Nicholas Hardcastle
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Jeremy Booth
- Department of Radiation Oncology, Northern Sydney Cancer Centre, Sydney, NSW, Australia
| | - Val Gebski
- University of Sydney NHMRC Clinical Trials Centre, Sydney, NSW, Australia
| | - Tim Wang
- Department of Radiation Oncology, Crown Princess Mary Cancer Centre, Sydney, NSW, Australia
| | - Paul Keall
- ACRF Image X Institute, Sydney, NSW, Australia
- Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
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30
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Liu HYH, Lee YYD, Sridharan S, Choong ES, Le H, Wang W, Khor R, Chu J, Oar A, Mott R, Smart J, Jenkins T, Anderson N, Cross S, Loo KF, Wigg A, Stuart K, Pryor D. Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi-institutional patterns of practice review. J Med Imaging Radiat Oncol 2021; 65:365-373. [PMID: 33890425 DOI: 10.1111/1754-9485.13184] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 03/29/2021] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions. METHODS This was a multi-institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated. RESULTS Three hundred and seventeen patients were evaluated with a median age of 67 years (range, 32-90). Liver cirrhosis was present in 88.6%, baseline Child-Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10-280). 63.1% had early-stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced-stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10 ) delivered was 85.5 Gy for early-stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100-120 Gy BED10 (32.8%). CONCLUSION SBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT.
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Affiliation(s)
- Howard Yu-Hao Liu
- Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Yoo-Young Dominique Lee
- Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Swetha Sridharan
- Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia
| | - Ee Siang Choong
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia
| | - Hien Le
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Wei Wang
- Department of Radiation Oncology, The Crown Princess Mary Cancer Centre, Sydney, New South Wales, Australia.,Department of Radiation Oncology, Nepean Cancer Care Centre, Sydney, New South Wales, Australia
| | - Richard Khor
- Department of Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Melbourne, Victoria, Australia
| | - Julie Chu
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Andrew Oar
- Icon Cancer Centre, Gold Coast University Hospital, Gold Coast, Queensland, Australia
| | - Rebekah Mott
- Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Joanne Smart
- Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia
| | - Trish Jenkins
- Department of Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Melbourne, Victoria, Australia
| | - Nigel Anderson
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Shamira Cross
- Department of Radiation Oncology, The Crown Princess Mary Cancer Centre, Sydney, New South Wales, Australia.,Department of Radiation Oncology, Nepean Cancer Care Centre, Sydney, New South Wales, Australia
| | - Kee Fong Loo
- Hepatology and Liver Transplantation Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Alan Wigg
- Hepatology and Liver Transplantation Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Katherine Stuart
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - David Pryor
- Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Icon Cancer Centre, Greenslopes Hospital, Brisbane, Queensland, Australia
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31
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Jackson WC, Hartman HE, Gharzai LA, Maurino C, Karnak DM, Mendiratta-Lala M, Parikh ND, Mayo CS, Haken RKT, Schipper MJ, Cuneo KC, Lawrence TS. The Potential for Midtreatment Albumin-Bilirubin (ALBI) Score to Individualize Liver Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 2021; 111:127-134. [PMID: 33878421 DOI: 10.1016/j.ijrobp.2021.04.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 03/29/2021] [Accepted: 04/11/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT). METHODS AND MATERIALS Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board-approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models. RESULTS In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P = .02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P = .04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P = .003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not. CONCLUSIONS Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values.
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Affiliation(s)
| | | | | | | | | | | | - Neehar D Parikh
- Gastroenterology, University of Michigan Ann Arbor, Michigan
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Boldrini L, Corradini S, Gani C, Henke L, Hosni A, Romano A, Dawson L. MR-Guided Radiotherapy for Liver Malignancies. Front Oncol 2021; 11:616027. [PMID: 33869001 PMCID: PMC8047407 DOI: 10.3389/fonc.2021.616027] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology.
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Affiliation(s)
- Luca Boldrini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Cihan Gani
- Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University, Tübingen, Germany
| | - Lauren Henke
- Department of Radiation Oncology, Washington University in St Louis, St Louis, MO, United States
| | - Ali Hosni
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Angela Romano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italy
| | - Laura Dawson
- Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
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33
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Shanker MD, Liu HY, Lee YY, Stuart KA, Powell EE, Wigg A, Pryor DI. Stereotactic radiotherapy for hepatocellular carcinoma: Expanding the multidisciplinary armamentarium. J Gastroenterol Hepatol 2021; 36:873-884. [PMID: 32632941 DOI: 10.1111/jgh.15175] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/23/2020] [Accepted: 07/01/2020] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Long-term prognosis remains poor with treatment options frequently limited by advanced tumor stage, tumor location, or underlying liver dysfunction. Stereotactic ablative body radiotherapy (SABR) utilizes technological advances to deliver highly precise, tumoricidal doses of radiation. There is an emerging body of literature on SABR in HCC demonstrating high rates of local control in the order of 80-90% at 3 years. SABR is associated with a low risk of radiation-induced liver disease or decompensation in appropriately selected HCC patients with compensated liver function and is now being incorporated into guidelines as an additional treatment option. This review outlines the emerging role of SABR in the multidisciplinary management of HCC and summarizes the current evidence for its use as an alternative ablative option for early-stage disease, as a bridge to transplant, and as palliation for advanced-stage disease. We outline specific considerations regarding patient selection, toxicities, and response assessment. Finally, we compare current international guidelines and recommendations for the use of SABR and summarize ongoing studies.
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Affiliation(s)
- Mihir D Shanker
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Howard Y Liu
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Yoo Young Lee
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Katherine A Stuart
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Elizabeth E Powell
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Alan Wigg
- Hepatology and Liver Transplantation Medicine Unit, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - David I Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
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Brown E, Muscat E, O’Connor P, Liu H, Lee Y, Pryor D. Intrafraction cone beam computed tomography verification of breath hold during liver stereotactic radiation therapy. J Med Radiat Sci 2021; 68:52-59. [PMID: 33025723 PMCID: PMC7890922 DOI: 10.1002/jmrs.441] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 09/16/2020] [Accepted: 09/17/2020] [Indexed: 01/02/2023] Open
Abstract
INTRODUCTION Intrafraction imaging is an Elekta feature that enables cone beam computed tomography (CBCT) acquisition simultaneously with treatment arc delivery. It has facilitated the introduction of breath-hold (BH) gated stereotactic body radiation therapy (SBRT) by enabling visualisation of tumour and organs at risk during treatment. The aims of this study were to assess BH reproducibility and use intrafraction CBCT (IF-CBCT) to quantify any variation in diaphragm position (diaphragmatic feathering) during the multiple BHs performed during each arc. METHODS IF-CBCTs for consecutive liver SBRT patients where BH was achieved using the Elekta Active Breathing Control (ABC) system were retrospectively evaluated. Average intrafraction couch shifts for deep-inspiration BH (DIBH) or end-expiration BH (EEBH) were recorded as an indication of reproducibility. Diaphragmatic feathering was quantified by measuring the difference between the most superior and inferior visible edges of the diaphragm on IF-CBCTs. RESULTS A total of 212 images from 30 patients were reviewed. Twenty-two (73.3%) patients were treated in EEBH. The mean intrafraction shift was similar between DIBH and EEBH groups with the largest mean shift of 0.22cm occurring in the superior-inferior direction. Mean diaphragmatic feathering was similar between the DIBH and EEBH groups, 0.09cm (0-0.44cm) and 0.14cm (0-1.89cm) respectively. A higher percentage of EEBH patients demonstrated no diaphragmatic feathering throughout treatment compared with DIBH patients (31.8% vs 25%). CONCLUSION The results of this study indicate that BH is reproducible in both DIBH and EEBH for liver SBRT treatment using the ABC system. Appropriate patient selection and BH coaching prior to CT simulation are critical to its success.
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Affiliation(s)
- Elizabeth Brown
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
- School of Clinical SciencesQueensland University of TechnologyBrisbaneQueenslandAustralia
| | - Erika Muscat
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
| | - Patrick O’Connor
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
- Radiation Oncology DepartmentSunshine Coast University HospitalAdem Crosby Centre, BirtinyaQueenslandAustralia
| | - Howard Liu
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
- School of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
| | - Yoo‐Young Lee
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
- School of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
| | - David Pryor
- Radiation OncologyPrincess Alexandra HospitalBrisbaneQueenslandAustralia
- School of MedicineUniversity of QueenslandBrisbaneQueenslandAustralia
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35
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Liu HM, Tan HY, Lin Y, Xu BN, Zhao WH, Xie YA. MicroRNA-1271-5p inhibits cell proliferation and enhances radiosensitivity by targeting CDK1 in hepatocellular carcinoma. J Biochem 2021; 167:513-524. [PMID: 32275316 DOI: 10.1093/jb/mvz114] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 12/24/2019] [Indexed: 12/13/2022] Open
Abstract
This study aims to determine whether miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity by targeting cyclin-dependent kinase 1 (CDK1) in hepatocellular carcinoma (HCC). Its expression levels in the HCC cell lines were significantly lower than those in normal human liver cell line. Bioinformatics analysis indicated CDK1 was a potential target of miR-1271-5p. Dual-Luciferase Reporter Assay confirmed that CDK1 is a direct target gene of miR-1271-5p. With overexpression of miR-1271-5p in SMMC-7721 and HuH-7 cells, cell proliferation was decreased, radiosensitivity was enhanced, cell cycle distribution was altered and the growth of transplanted tumours in nude mice was significantly reduced. miR-1271-5p overexpression enhanced radiosensitivity, which could be reduced by CDK1 overexpression. Overall, our findings suggested that miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity of HCC cell lines by targeting CDK1.
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Affiliation(s)
- Hong-Mei Liu
- Research Department, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.,Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Hua-Yan Tan
- Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Yue Lin
- Research Department, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Bei-Ning Xu
- Research Department, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Wen-Hua Zhao
- Research Department, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
| | - Yu-An Xie
- Research Department, Affiliated Cancer Hospital of Guangxi Medical University and Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China.,The Maternal & Health Hospital, The Children's Hospital, The Obstetrics & Gynecology Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
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Li S, Guo JH, Lu J, Wang C, Wu H, Wang H, Zha J, Fan R. I 125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis. Cancer Radiother 2021; 25:340-349. [PMID: 33455874 DOI: 10.1016/j.canrad.2020.12.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 11/10/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE A meta-analysis aimed to systematically evaluate the safety and efficiency of I125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS The Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. RESULTS Totally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I125 irradiation stent improved the cumulative stent patency rates in 6months [OR=1.65, 95% CI (1.32-2.05), P<0.001] and 12months [OR=2.55, 95% CI (1.90-3.42), P<0.001] and the survival rates in 6months [OR=1.77, 95% CI (1.41-2.22), P<0.001], 12months [OR=3.14, 95% CI (2.24-4.40), P<0.001] and 24months [OR=7.39, 95% CI (3.55-15.41), P<0.001]. However, there was no difference in the objective response rate of PVTT [OR=1.13, 95% CI (0.87-1.48), P=0.365], main portal venous pressure and the occurrence adverse event [OR=0.88, CI=0.72-1.08, P=0.212] between two groups. CONCLUSION I125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.
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Affiliation(s)
- S Li
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J-H Guo
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J Lu
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - C Wang
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - H Wu
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - H Wang
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - J Zha
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
| | - R Fan
- Department of Interventional Radiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
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MRI-guided stereotactic radiation therapy for hepatocellular carcinoma: a feasible and safe innovative treatment approach. J Cancer Res Clin Oncol 2021; 147:2057-2068. [PMID: 33398447 DOI: 10.1007/s00432-020-03480-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 11/22/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors. METHODS We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment-response assessment. RESULTS Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1-25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child-Pugh before and after treatment remained unchanged in all but one patient. CONCLUSION MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.
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Kim N, Cheng J, Huang WY, Kimura T, Zeng ZC, Lee VHF, Kay CS, Seong J. Dose-Response Relationship in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: A Pooled Analysis of an Asian Liver Radiation Therapy Group Study. Int J Radiat Oncol Biol Phys 2020; 109:464-473. [PMID: 33229165 DOI: 10.1016/j.ijrobp.2020.09.038] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 09/13/2020] [Accepted: 09/16/2020] [Indexed: 02/08/2023]
Abstract
PURPOSE Despite the worldwide implementation of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC), there is a lack of consensus guideline on prescription dose. Herein, this multinational study aimed to investigate the effects of the prescribed radiation dose on oncologic outcomes of SBRT for HCC. METHODS AND MATERIALS The multi-institutional retrospective cohort included 510 patients treated with SBRT between 2010 and 2016. All relevant clinical factors and factors related to SBRT were analyzed to evaluate freedom from local progression (FFLP) and overall survival (OS). Based on a biologically effective dose (BED) cutoff value of 100 Gy, 198 tumors were selected from each group in propensity score matching (PSM). RESULTS Baseline characteristics in the BED <100 Gy group were unfavorable (Child-Pugh class B, 19%; advanced stage, 72%; median tumor size was 4 cm) compared with the BED ≥100 Gy group. With a median follow-up of 22 (interquartile range, 9.8-37.6) months, the 2-year FFLP and OS rates were 77% and 73%, respectively. Patients treated with a BED ≥100 Gy showed better rates of 2-year FFLP and OS than patients treated with a BED <100 Gy (FFLP, 89% vs 69%; OS, 80% vs 67%; P < .001). In the multivariable analysis before and after PSM, BED ≥100 Gy was identified as the main prognostic factor for both FFLP and OS (P < .01). Additionally, a dose-response relationship was observed between FFLP and BED (odds ratio, 0.92 per 5 Gy, P = .048). CONCLUSIONS A BED ≥100 Gy was significantly associated with outcomes, and a dose-response relationship was observed between local tumor progression and BED. Given that SBRT is being increasingly used in HCC, detailed consensus guidelines regarding SBRT dose prescription should be established.
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Affiliation(s)
- Nalee Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jason Cheng
- Department of Radiation Oncology, National Taiwan University Hospital, Taipei City, Taiwan
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Tomoki Kimura
- Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan
| | - Zhao Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Victor H F Lee
- Department of Radiation Oncology, University of Hong Kong, Hong Kong, People's Republic of China
| | - Chul Seung Kay
- Department of Radiation Oncology, Incheon St. Mary Hospital, Incheon, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Prince D, Liu K, Xu W, Chen M, Sun JY, Lu XJ, Ji J. Management of patients with intermediate stage hepatocellular carcinoma. Ther Adv Med Oncol 2020; 12:1758835920970840. [PMID: 33224278 PMCID: PMC7649909 DOI: 10.1177/1758835920970840] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 10/08/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.
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Affiliation(s)
- David Prince
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Liver Injury and Cancer Program, The Centenary Institute, Sydney, NSW, Australia
| | - Weiqi Xu
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Jin-Yu Sun
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Sparkfire Scientific Research Group, Nanjing Medical University, Nanjing, China
| | - Xiao-Jie Lu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui 323000, China
- Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/The Central Hospital of Zhejiang Lishui, Lishui, 323000, China
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Kim N, Cheng J, Jung I, Liang JD, Shih YL, Huang WY, Kimura T, Lee VHF, Zeng ZC, Zhenggan R, Kay CS, Heo SJ, Won JY, Seong J. Stereotactic body radiation therapy vs. radiofrequency ablation in Asian patients with hepatocellular carcinoma. J Hepatol 2020; 73:121-129. [PMID: 32165253 DOI: 10.1016/j.jhep.2020.03.005] [Citation(s) in RCA: 126] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 02/26/2020] [Accepted: 03/02/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.
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Affiliation(s)
- Nalee Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea
| | - Jason Cheng
- Department of Radiation Oncology, National Taiwan University Hospital, Taiwan
| | - Inkyung Jung
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ja Der Liang
- Department of Internal Medicine, National Taiwan University Hospital, Taiwan
| | - Yu Lueng Shih
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan
| | - Wen-Yen Huang
- Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taiwan
| | - Tomoki Kimura
- Department of Radiation Oncology, Hiroshima University Hospital, Japan
| | - Victor H F Lee
- Department of Radiation Oncology, The University of Hong Kong, Hong Kong
| | - Zhao Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, China
| | - Ren Zhenggan
- Department of Medical Hepatology, Zhongshan Hospital, Fudan University, China
| | - Chul Seung Kay
- Department of Radiation Oncology, Incheon St. Mary Hospital, Republic of Korea
| | - Seok Jae Heo
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Yoon Won
- Department of Interventional Radiology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Republic of Korea.
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Mathew AS, Atenafu EG, Owen D, Maurino C, Brade A, Brierley J, Dinniwell R, Kim J, Cho C, Ringash J, Wong R, Cuneo K, Feng M, Lawrence TS, Dawson LA. Long term outcomes of stereotactic body radiation therapy for hepatocellular carcinoma without macrovascular invasion. Eur J Cancer 2020; 134:41-51. [PMID: 32460180 DOI: 10.1016/j.ejca.2020.04.024] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 04/16/2020] [Accepted: 04/21/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America. METHODS Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates. RESULTS In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%. CONCLUSIONS SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.
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Affiliation(s)
- Ashwathy Susan Mathew
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Eshetu G Atenafu
- Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Dawn Owen
- Department of Radiation Oncology, University of Michigan, Michigan, United States
| | - Chris Maurino
- Department of Radiation Oncology, University of Michigan, Michigan, United States
| | - Anthony Brade
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - James Brierley
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Robert Dinniwell
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - John Kim
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Charles Cho
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Jolie Ringash
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Rebecca Wong
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Kyle Cuneo
- Department of Radiation Oncology, University of Michigan, Michigan, United States
| | - Mary Feng
- Department of Radiation Oncology, University of Michigan, Michigan, United States
| | - Theodore S Lawrence
- Department of Radiation Oncology, University of Michigan, Michigan, United States
| | - Laura A Dawson
- Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
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Liu HY, Lee Y, McLean K, Leggett D, Hodgkinson P, Fawcett J, Mott R, Stuart K, Pryor D. Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma - Initial Experience From an Australian Liver Cancer Service. Clin Oncol (R Coll Radiol) 2020; 32:e194-e202. [PMID: 32345457 DOI: 10.1016/j.clon.2020.04.004] [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] [Received: 12/17/2019] [Revised: 03/24/2020] [Accepted: 04/06/2020] [Indexed: 12/17/2022]
Abstract
AIMS Intrahepatic progression remains the predominant mode of cancer-related death in hepatocellular carcinoma (HCC) underscoring the need for effective local therapies. We report our initial experience with liver stereotactic body radiotherapy (SBRT) in the management of early to advanced stage HCC at an Australian tertiary liver cancer service. MATERIALS AND METHODS Patients with liver-confined HCC unsuitable for surgical resection or thermal ablation treated with SBRT between October 2013 and December 2018 were retrospectively evaluated. The primary end point was freedom from local progression. Secondary end points were progression-free survival, disease-specific survival, overall survival and toxicity. RESULTS Ninety-six patients were treated for 112 lesions (median size 3.8 cm, range 1.5-17 cm). The median follow-up was 13 months (range 3-65). Forty-six patients had received prior local therapies (median 1, range 1-5), 83 (86%) patients had cirrhosis with baseline Child-Pugh scores of A (88%) and B7-8 (12%). Fifty-nine (61%) patients had Barcelona Clinic Liver Cancer (BCLC) stage 0/A disease and 37 (39%) had stage B/C. Macrovascular invasion was present in 20 (21%). The median biologically effective dose (BED10) was 86 and 60 Gy for the BCLC 0/A and B/C cohorts, respectively. Freedom from local progression at 18 months was 94% for BCLC 0/A and 74% for BCLC B/C. Progression-free survival and overall survival at 12 months were 80 and 95% for BCLC 0/A and 40 and 71% for BCLC B/C, respectively. Five patients (7%) with cirrhosis and without disease progression had an increase in Child-Pugh score >1 within 3 months of SBRT, four of whom had intercurrent infections. Clinical toxicities grade ≥2 were reported in 20% of patients. CONCLUSION SBRT is an effective ablative modality for early stage HCC with low rates of significant toxicity. Lower dose SBRT can provide durable local control for advanced stage HCC. However, out-of-field relapse remains common, providing a rationale to investigate SBRT in combination with other therapies.
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Affiliation(s)
- H Y Liu
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia.
| | - Y Lee
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia
| | - K McLean
- Department of Diagnostic Radiology, Princess Alexandra Hospital, Brisbane, Australia
| | - D Leggett
- Department of Diagnostic Radiology, Princess Alexandra Hospital, Brisbane, Australia
| | - P Hodgkinson
- Department of Hepatobiliary Surgery, Princess Alexandra Hospital, Brisbane, Australia
| | - J Fawcett
- Department of Hepatobiliary Surgery, Princess Alexandra Hospital, Brisbane, Australia
| | - R Mott
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia
| | - K Stuart
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
| | - D Pryor
- Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Queensland, Australia
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Zhao J, Zeng L, Wu Q, Wang L, Lei J, Luo H, Yi F, Wei Y, Yu J, Zhang W. Stereotactic Body Radiotherapy Combined with Transcatheter Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review. Chemotherapy 2020; 64:248-258. [PMID: 32320982 DOI: 10.1159/000505739] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/06/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The superiority of stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) compared to SBRT alone as the first-line therapy for unresectable hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to compare the efficiency and safety of SBRT combined with TACE (ST group) and SBRT alone (SA group). METHODS We searched PubMed, Ovid Medline, Web of Science, Scopus, The Cochrane Library, ScienceDirect, EMBASE, Google Scholar, and CNKI (China National Knowledge Infrastructure) for related studies. We analyzed overall survival (OS), local control survival (LCS), progression-free survival (PFS), the response rate and adverse effects (AEs) between the 2 groups. RESULTS Ten articles were included, with a total of 980 patients. The results showed that the ST (SBRT + TACE) group had a longer OS (95% CIs 0.60-0.85, p = 0.0002), a higher 5-year OS rate (95% CI 1.01-2.04, p = 0.04), a higher rate of complete response (95% CI 1.08-1.90, p = 0.01), and a higher disease control rate (95% CI 1.02-1.16, p = 0.02) than the SA (SBRT alone) group. No significant difference was found in LCS, PFS and total AEs of all grades and grades 3-5 AEs between the 2 groups. In the subgroup analysis, the patients with HCC + PVTT or treated with SBRT followed by TACE in the ST group had the same OS as those in the SA group, and the patients in the ST group had a higher incidence rate of leukopenia and fever than those in the SA group. CONCLUSION SBRT + TACE appears to be more effective than SBRT alone in treating unresectable HCC. However, its higher incidence rate of leukopenia and fever need to be monitored.
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Affiliation(s)
- Jiani Zhao
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Department of Nuclear Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Lianli Zeng
- Department of Nuclear Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.,Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qian Wu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Li Wang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Jun Lei
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongliang Luo
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fengming Yi
- Department of Digestive Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yiping Wei
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jiao Yu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China,
| | - Wenxiong Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Sun J, Zhang A, Li W, Wang Q, Wang J, Fan Y, Sun Y, Li D, Zhang D, Duan X. CyberKnife Stereotactic Body Radiation Therapy as an Effective Treatment for Hepatocellular Carcinoma Patients With Decompensated Cirrhosis. Front Oncol 2020; 10:100. [PMID: 32158688 PMCID: PMC7052044 DOI: 10.3389/fonc.2020.00100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/20/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose: The aim of our study was to evaluate the curative effect and safety of CyberKnife stereotactic body radiation therapy in treating decompensated cirrhosis hepatocellular carcinoma (HCC) patients. Methods: From March 2011 to December 2015, 32 HCC patients who refused or were ineligible for other treatments were treated with CyberKnife stereotactic body radiation therapy. Among these patients, 17 were Child-Pugh score 7 (53.13%), 7 were Child-Pugh score 8 (21.87%), 4 were Child-Pugh score 9 (12.50%), and 4 were Child-Pugh score 10 (12.50%). A total dose of 45-54 Gy in 5-10 fractions was given according to the location of lesions. Results: The median follow-up period was 30 months (8-46 months). By July 2019, the tumors were recurrent or metastasized in 17 patients. The overall survival rates of 1, 2, and 3 years were 84.4, 61.8, and 46.0%, respectively. After 1, 2, and 3 years, the local control rates were 92.9%. The progression-free survival rates of the 1, 2, and 3-year treatments were 73.8, 44.6, and 33.4%, respectively. Conclusions: CyberKnife stereotactic body radiation therapy was an effective option for HCC patients with decompensated cirrhosis. The liver injury occurrence rate was acceptable in our study.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Xuezhang Duan
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), Beijing, China
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Sun J, Ouyang C, Chang X, Zhang A, Wang Q, Li W, Zhang D, Wang J, Li D, Duan X. Repeated CyberKnife stereotactic body radiation therapy in hepatocellular carcinoma. Radiat Oncol 2020; 15:10. [PMID: 31918728 PMCID: PMC6953301 DOI: 10.1186/s13014-020-1457-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 01/05/2020] [Indexed: 12/14/2022] Open
Abstract
Background To explore the survival and side effects of repeated CyberKnife stereotactic body radiation therapy (CK-SBRT) on hepatocellular carcinoma patients. Methods 24 HCC patients were collected at The Fifth Medical Center of PLA General Hospital from November 2011 to July 2016. They received second-course CK-SBRT with a prescribed dose of 50(48–55) Gy/5-8fx, and a single dose of 10 (7–11) Gy/fx. Cumulative overall survival rates (OS), progression-free survival rates (PFS) and local control rates (LC) were calculated by Kaplan-Meier method. Results All patients finished their radiotherapy plans. The 1-,2- and 3-year cumulative OS rate were 95.8,81.1 and 60.8%. The 1-,2- and 3-year LC rate were 95.5,90.7 and 90.7%, respectively. The 1-, 2- and 3-year PFS were 74.8, 49.2 and 39.4%, respectively. 16 patients complained of fatigue during second-course therapy, 2 patients showed Grade 2 gastrointestinal reaction, 1 patient was diagnosed radiation-induced liver disease and none died. PFS was significantly higher in the interval time < 12 months group than in the interval time ≥ 12 months group (p = 0.030). Conclusions It is preliminarily believed that re-CK-SBRT is an effective and safe treatment for HCC patients, but the treatment criteria should be strictly controlled.
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Affiliation(s)
- Jing Sun
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Can Ouyang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Xiaoyun Chang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Aimin Zhang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Quan Wang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Wengang Li
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Dan Zhang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Jia Wang
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Dong Li
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China
| | - Xuezhang Duan
- Department of Radiation Oncology, The Fifth Medical Center of PLA General Hospital (302 Military Hospital), Beijing, 100039, China.
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Tanaka O, Kojima T, Ohbora A, Makita C, Taniguchi T, Ono K, Matsuo M, Nagata Y. Scores of Child-Pugh Classification Impact Overall Survival After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors. J Clin Exp Hepatol 2020; 10:101-105. [PMID: 32189924 PMCID: PMC7068027 DOI: 10.1016/j.jceh.2019.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/09/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Stereotactic body radiotherapy (SBRT) delivers high-dose radiation to tumor tissues in few fractions, thereby reducing radiation damage to at-risk organs. There are more potential effects of SBRT owing to the higher biological equivalent dose delivered. Herein, we retrospectively analyzed its effectiveness and toxicity at our institution. METHODS Data from patients with hepatocellular carcinoma (HCC; n = 10) and liver metastases (n = 10) who underwent SBRT (total dose of 30-50 Gy in 5-10 fractions) between 2013 and 2016 were analyzed. Adverse events were recorded at the end of RT, 6 months after treatment, or upon death. Overall survival (OS) was calculated according to the biological effective dose (BED α/β = 10) and liver function (Child-Pugh [CP] classification 5 or 6 vs. 7 or 8) after SBRT, using Kaplan-Meier analyses. RESULTS Of the 20 patients, 6 declined the CP classification score after SBRT; grade 3 adverse events were not seen in any patient. A higher OS rate was seen in patients receiving a higher BED and in those with better CP classification after SBRT. Kaplan-Meier survival analysis yielded a median OS of 401 days and 1- and 2-year OS of 45% and 15%, respectively. CONCLUSION The higher BED was significantly associated with tumor control, and there were no differences in the tumor control rate between HCC and metastatic tumors. Changes in CP scores after SBRT also affected the survival rate. Good liver function may permit multiple rounds of SBRT.
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Affiliation(s)
- Osamu Tanaka
- Asahi University Hospital, Department of Radiation Oncology, Gifu, Japan,Address for correspondence: Osamu Tanaka, M.D. Department of Radiation Oncology, Asahi University Hospital, 3-23 Hashimoto-cho, Gifu city, Gifu, 500-8523, Japan.
| | - Takao Kojima
- Asahi University Hospital, Department of Gastroenterology, Gifu, Japan
| | - Akihiro Ohbora
- Asahi University Hospital, Department of Gastroenterology, Gifu, Japan
| | - Chiyoko Makita
- Gifu Prefectural General Medical Center, Department of Radiation Oncology, Gifu, Japan
| | - Takuya Taniguchi
- Asahi University Hospital, Department of Radiation Oncology, Gifu, Japan
| | - Kousei Ono
- Asahi University Hospital, Department of Radiation Oncology, Gifu, Japan
| | - Masayuki Matsuo
- Gifu University Hospital, Department of Radiology, Gifu, Japan
| | - Yasushi Nagata
- Hiroshima University Hospital, Department of Radiation Oncology, Hiroshima, Japan
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47
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Jang WI, Bae SH, Kim MS, Han CJ, Park SC, Kim SB, Cho EH, Choi CW, Kim KS, Hwang S, Kim JH, Chang AR, Park Y, Kim ES, Kim WC, Jo S, Park HJ. A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy. Cancer 2019; 126:363-372. [PMID: 31747476 DOI: 10.1002/cncr.32502] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 07/10/2019] [Accepted: 07/13/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.
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Affiliation(s)
- Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Sun Hyun Bae
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Chul Ju Han
- Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Su Cheol Park
- Department of Internal Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Sang Bum Kim
- Department of General Surgery, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Eung-Ho Cho
- Department of General Surgery, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Chul Won Choi
- Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Kyung Su Kim
- Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Sangyoun Hwang
- Department of Internal Medicine, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
| | - Jin Ho Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea
| | - A Ram Chang
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Younghee Park
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Eun Seog Kim
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Woo Chul Kim
- Department of Radiation Oncology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| | - Sunmi Jo
- Department of Radiation Oncology, Haeundae Paik Hospital, Inje University School of Medicine, Busan, Korea
| | - Hae Jin Park
- Department of Radiation Oncology, Hanyang University Hospital, Seoul, Korea
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48
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Stereotactic body radiotherapy in patients with hepatocellular carcinoma in a multimodal treatment setting. Strahlenther Onkol 2019; 196:334-348. [DOI: 10.1007/s00066-019-01540-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Accepted: 10/23/2019] [Indexed: 12/24/2022]
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49
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Lewis AR, Padula CA, McKinney JM, Toskich BB. Ablation plus Transarterial Embolic Therapy for Hepatocellular Carcinoma Larger than 3 cm: Science, Evidence, and Future Directions. Semin Intervent Radiol 2019; 36:303-309. [PMID: 31680721 DOI: 10.1055/s-0039-1697641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Thermal ablation is widely regarded as definitive therapy for early-stage hepatocellular carcinoma, but its efficacy decreases in tumors greater than 3 cm. Extensive clinical studies have supported improved outcomes provided through combining transarterial embolic therapy with ablation in the treatment of larger tumors. This article will provide a survey of the science and data for combination therapy in both thermal and nonthermal ablation modalities, as well as describe emerging applications.
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Affiliation(s)
- Andrew R Lewis
- Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
| | - Carlos A Padula
- Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
| | - J Mark McKinney
- Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
| | - Beau B Toskich
- Division of Interventional Radiology, Department of Radiology, Mayo Clinic, Jacksonville, Florida
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50
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Skouboe S, Poulsen PR, Muurholm CG, Worm E, Hansen R, Høyer M, Ravkilde T. Simulated real‐time dose reconstruction for moving tumors in stereotactic liver radiotherapy. Med Phys 2019; 46:4738-4748. [DOI: 10.1002/mp.13792] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/13/2019] [Accepted: 08/19/2019] [Indexed: 12/21/2022] Open
Affiliation(s)
- Simon Skouboe
- Department of Oncology Aarhus University Hospital Aarhus N 8200Denmark
| | - Per Rugaard Poulsen
- Department of Oncology Aarhus University Hospital Aarhus N 8200Denmark
- Danish Center for Particle Therapy Aarhus University Hospital Aarhus N 8200 Denmark
| | | | - Esben Worm
- Department of Medical Physics Aarhus University Hospital Aarhus N 8200Denmark
| | - Rune Hansen
- Department of Medical Physics Aarhus University Hospital Aarhus N 8200Denmark
| | - Morten Høyer
- Danish Center for Particle Therapy Aarhus University Hospital Aarhus N 8200 Denmark
| | - Thomas Ravkilde
- Department of Medical Physics Aarhus University Hospital Aarhus N 8200Denmark
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