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1
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Amit U, Mohiuddin JJ, Wojcieszynski AP, Harton J, Williams G, Manjunath S, Grandhi N, Doucette A, Plastaras JP, Metz JM, Ben-Josef E. Radiation dose is associated with improved local control for large, but not small, hepatocellular carcinomas. Radiat Oncol 2023; 18:133. [PMID: 37568200 PMCID: PMC10422771 DOI: 10.1186/s13014-023-02318-0] [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: 01/13/2023] [Accepted: 07/06/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND With advances in understanding liver tolerance, conformal techniques, image guidance, and motion management, dose-escalated radiotherapy has become a potential treatment for inoperable hepatocellular carcinoma (HCC). We aimed to evaluate the possible impact of biologically effective dose (BED) on local control and toxicity among patients with HCC. METHODS AND MATERIALS Patients treated at our institution from 2009 to 2018 were included in this retrospective analysis if they received definitive-intent radiotherapy with a nominal BED of at least 60 Gy. Patients were stratified into small and large tumors using a cutoff of 5 cm, based on our clinical practice. Toxicity was assessed using ALBI scores and rates of clinical liver function deterioration. RESULTS One hundred and twenty-eight patients were included, with a mean follow-up of 16 months. The majority of patients (90.5%) had a good performance status (ECOG 0-1), with Child-Pugh A (66.4%) and ALBI Grade 2 liver function at baseline (55.4%). Twenty (15.6%) patients had a local recurrence in the irradiated field during the follow-up period. Univariate and multivariate Cox proportional hazard analyses showed that only BED significantly predicted local tumor recurrence. Higher BED was associated with improved local control in tumors with equivalent diameters over 5 cm but not in smaller tumors. There was no difference in liver toxicity between the low and high-dose groups. CONCLUSIONS Higher radiotherapy dose is associated with improved local control in large tumors but not in tumors smaller than 5 cm in diameter. High-dose radiotherapy was not associated with increased liver toxicity.
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Affiliation(s)
- Uri Amit
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA.
- Department of Radiation Oncology, Tel Aviv Medical Center, Tel Aviv, Israel.
| | - Jahan J Mohiuddin
- Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
- Southeast Radiation Oncology Group, Charlotte, NC, USA
| | | | | | - Graeme Williams
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA
| | - Shwetha Manjunath
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA
| | - Nikhil Grandhi
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Abigail Doucette
- Abramson Cancer Center, Perelman School of Medicine, Philadelphia, PA, USA
| | - John P Plastaras
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA
| | - James M Metz
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA
| | - Edgar Ben-Josef
- Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, PA, USA
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2
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Jagtap J, Audi S, Razeghi-Kondelaji MH, Fish BL, Hansen C, Narayan J, Gao F, Sharma G, Parchur AK, Banerjee A, Bergom C, Medhora M, Joshi A. A rapid dynamic in vivo near-infrared fluorescence imaging assay to track lung vascular permeability after acute radiation injury. Am J Physiol Lung Cell Mol Physiol 2021; 320:L436-L450. [PMID: 33404364 DOI: 10.1152/ajplung.00066.2020] [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] [Indexed: 01/22/2023] Open
Abstract
To develop a dynamic in vivo near-infrared (NIR) fluorescence imaging assay to quantify sequential changes in lung vascular permeability-surface area product (PS) in rodents. Dynamic NIR imaging methods for determining lung vascular permeability-surface area product were developed and tested on non-irradiated and 13 Gy irradiated rats with/without treatment with lisinopril, a radiation mitigator. A physiologically-based pharmacokinetic (PBPK) model of indocyanine green (ICG) pulmonary disposition was applied to in vivo imaging data and PS was estimated. In vivo results were validated by five accepted assays: ex vivo perfused lung imaging, endothelial filtration coefficient (Kf) measurement, pulmonary vascular resistance measurement, Evan's blue dye uptake, and histopathology. A PBPK model-derived measure of lung vascular permeability-surface area product increased from 2.60 ± 0.40 [CL: 2.42-2.78] mL/min in the non-irradiated group to 6.94 ± 8.25 [CL: 3.56-10.31] mL/min in 13 Gy group after 42 days. Lisinopril treatment lowered PS in the 13 Gy group to 4.76 ± 6.17 [CL: 2.12-7.40] mL/min. A much higher up to 5× change in PS values was observed in rats exhibiting severe radiation injury. Ex vivo Kf (mL/min/cm H2O/g dry lung weight), a measure of pulmonary vascular permeability, showed similar trends in lungs of irradiated rats (0.164 ± 0.081 [CL: 0.11-0.22]) as compared to non-irradiated controls (0.022 ± 0.003 [CL: 0.019-0.025]), with reduction to 0.070 ± 0.035 [CL: 0.045-0.096] for irradiated rats treated with lisinopril. Similar trends were observed for ex vivo pulmonary vascular resistance, Evan's blue uptake, and histopathology. Our results suggest that whole body dynamic NIR fluorescence imaging can replace current assays, which are all terminal. The imaging accurately tracks changes in PS and changes in lung interstitial transport in vivo in response to radiation injury.
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Affiliation(s)
- Jaidip Jagtap
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Said Audi
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin.,Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
| | | | - Brian L Fish
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Christopher Hansen
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Jayashree Narayan
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Feng Gao
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Gayatri Sharma
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Abdul K Parchur
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Anjishnu Banerjee
- Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Carmen Bergom
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Meetha Medhora
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin.,Department of Pulmonary Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Amit Joshi
- Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin.,Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin
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3
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Xin TY, Feng J, Chen SB, Chen X, Guo YY, Sun P, Chen YZ. Application of quantitative analysis of contrast-enhanced ultrasonography in the evaluation of acute radiation-induced liver damage. Exp Ther Med 2020; 19:2957-2962. [PMID: 32256781 PMCID: PMC7086196 DOI: 10.3892/etm.2020.8541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 01/10/2020] [Indexed: 11/06/2022] Open
Abstract
The aim of the present study was to evaluate the microcirculation perfusion in patients with acute radiation-induced liver damage (RILD) and explore the feasibility of non-invasive evaluation of RILD using quantitative analysis of contrast-enhanced ultrasound (CEUS). Patients who successfully underwent three-dimensional conformal intensity-modulated radiotherapy for abdominal tumors were selected. CEUS was performed on the liver prior to and 2, 3 and 4 weeks after exposure, and the time-intensity curve (TIC) was obtained by quantitative analysis of CEUS. The time to peak (TTP), gradient (Grad) and area under the curve (AUC) were analyzed offline. The Grad of the CEUS TIC was decreased and TTP increased with the prolongation of the irradiation duration, with statistically significant differences between the values in the 2-, 3- and 4-week groups vs. those prior to exposure (P<0.05), as well as among the values of the 2-, 3- and 4-week groups (P<0.05). Following irradiation, the AUC decreased gradually in the 2- and 3-week groups and increased in the 4-week group, with statistically significant differences compared with the AUC prior to irradiation (P<0.05). The quantitative analysis parameters of CEUS may be important reference parameters for the early diagnosis of acute RILD.
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Affiliation(s)
- Tian-You Xin
- Department of Ultrasound, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Jun Feng
- Department of Ultrasound, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Shu-Bo Chen
- Department of Oncology, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Xian Chen
- Department of Ultrasound, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Ya-Yun Guo
- Department of Ultrasound, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Ping Sun
- Department of Pathology, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| | - Ying-Zhen Chen
- Department of Ultrasound, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
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Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria. AJR Am J Roentgenol 2019; 213:1232-1239. [PMID: 31613663 DOI: 10.2214/ajr.18.20842] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE. The purpose of this study was to investigate whether, compared with traditional criteria, the modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapeutics (iRECIST) improves prediction of local tumor control and survival in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS. Fifty-one HCC lesions (mean size, 3.1 cm) treated with SBRT in 41 patients (mean age, 67 years) were retrospectively included. Each patient underwent CT or MRI before SBRT and at least once after SBRT. Best overall response was categorized using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), iRECIST, World Health Organization (WHO) criteria, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Lesions were then classified as local tumor control (i.e., stable disease, partial response, or complete response) or local treatment failure (i.e., progressive disease) by each tumor response criteria. Proportions of local tumor control were compared using the McNemar exact test. The 1-year overall survival was estimated using the Kaplan-Meier method. RESULTS. The median follow-up after SBRT was 21.0 months. The local tumor control rate was 94.1% (48/51) by iRECIST, 88.2% (45/51) by RECIST 1.1, 72.5% (37/51) by WHO criteria, 80.4% (41/51) by mRECIST, and 72.5% (37/51) by EASL criteria. The local tumor control rate was significantly higher according to iRECIST compared with WHO (p = 0.0010) and EASL (p = 0.0225) criteria. The 1-year survival rate for patients with local tumor control according to iRECIST (86.4%) was higher (although not statistically significant) compared with the 1-year survival rate for patients with local tumor control according to the other response criteria. CONCLUSION. iRECIST may provide more robust interpretation of HCC response after SBRT, yielding improved prediction of local tumor control and 1-year survival rates compared with traditional criteria.
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Takamatsu S, Kozaka K, Kobayashi S, Yoneda N, Yoshida K, Inoue D, Kitao A, Ogi T, Minami T, Kouda W, Kumano T, Fuwa N, Matsui O, Gabata T. Pathology and images of radiation-induced hepatitis: a review article. Jpn J Radiol 2018; 36:241-256. [DOI: 10.1007/s11604-018-0728-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 02/21/2018] [Indexed: 12/12/2022]
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6
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Kim J, Jung Y. Radiation-induced liver disease: current understanding and future perspectives. Exp Mol Med 2017; 49:e359. [PMID: 28729640 PMCID: PMC5565955 DOI: 10.1038/emm.2017.85] [Citation(s) in RCA: 144] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 02/03/2017] [Indexed: 02/06/2023] Open
Abstract
Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD. Despite efforts to develop suitable experimental animal models for RILD, current animal models rarely present hepatic veno-occlusive disease, the pathological hallmark of human RILD patients, resulting in highly variable results in RILD-related studies. Therefore, we introduce the concept and clinical characteristics of RILD and propose a feasible explanation for RILD pathogenesis. In addition, currently available animal models of RILD are reviewed, focusing on similarities with human RILD and clues to understanding the mechanisms of RILD progression. Based on these findings from RILD research, we present potential therapeutic strategies for RILD and prospects for future RILD studies. Therefore, this review helps broaden our understanding for developing effective treatment strategies for RILD.
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Affiliation(s)
- Jieun Kim
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, Republic of Korea
| | - Youngmi Jung
- Department of Integrated Biological Science, College of Natural Science, Pusan National University, Pusan, Republic of Korea.,Department of Biological Sciences, College of Natural Science, Pusan National University, Pusan, Republic of Korea
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7
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Liu H, Wang S, Wu Z, Huang Z, Chen WY, Yang Y, Cui J, Liu C, Zhao H, Guo J, Zhang P, Gao F, Li B, Cai J. Glibenclamide, a diabetic drug, prevents acute radiation induced liver injury of mice via up-regulating intracellular ROS and subsequently activating Akt-NF-κB pathway. Oncotarget 2017; 8:40568-40582. [PMID: 28380448 PMCID: PMC5522206 DOI: 10.18632/oncotarget.16501] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 02/15/2017] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Acute radiation-induced liver injury is a limitation for hepatoma radiotherapy. Come so far the clinical treatments are insufficient. The effective, specific, low toxicity and novel drugs are in powerful need. Glibenclamide is a common hypoglycemic. Some studies have revealed its relation with intracellular reactive oxygen species, the crucial mediator to radiation injury. This study is aimed to investigate if glibenclamide could act on the acute radiation-induced liver injury. RESULTS Glibenclamide mitigated acute radiation-induced liver injury of mice, indicating as regression of hepatocellular edema, reduction of hepatic sinusoid, decline in serum ALP level and reduction of hepatocellular apoptosis. Pretreatment of glibenclamide reduced the radiosensitivity of NCTC-1469 cells. In mechanism, glibenclamide elevated cells membrane potential to up-regulate intracellular reactive oxygen species. The increased reactive oxygen species subsequently activated Akt-NF-κB pathway to promote survival of irradiated cells. METHODS BALB/C male mice were intraperitoneal injected with glibenclamide 1 hour before hepatic irradiation. At designed time points the livers were taken to make histological study and bloods were collected to measure serum transaminase. With/without glibenclamide pretreatment the irradiated NCTC-1469 cells were tested apoptosis, viability and proliferation. By western blotting the involved molecules were detected. CONCLUSIONS Glibenclamide, prevents acute radiation-induced liver injury of mice via up-regulating intracellular reactive oxygen species and subsequently activating Akt-NF-κB pathway.
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Affiliation(s)
- Hu Liu
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Shichao Wang
- Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China
| | - Zhao Wu
- Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China
| | - Ziyun Huang
- Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China
| | - Wei You Chen
- Fifth Cadet Battalion of Naval Medicine Department, Second Military Medical University, Shanghai, China
| | - Yanyong Yang
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Jianguo Cui
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Cong Liu
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Hainan Zhao
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Jiaming Guo
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Pei Zhang
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Fu Gao
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Bailong Li
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Jianming Cai
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
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8
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Yu JI, Park HC. Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis. World J Gastroenterol 2016; 22:6851-6863. [PMID: 27570422 PMCID: PMC4974584 DOI: 10.3748/wjg.v22.i30.6851] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/01/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Although the current standard treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy (RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.
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9
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Dreher C, Høyer KI, Fode MM, Habermehl D, Combs SE, Høyer M. Metabolic liver function after stereotactic body radiation therapy for hepatocellular carcinoma. Acta Oncol 2016; 55:886-91. [PMID: 26878669 DOI: 10.3109/0284186x.2015.1137352] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Purpose The time course of changes of the liver function after stereotactic body radiotherapy (SBRT) was analyzed in patients treated for non-resectable hepatocellular carcinoma (HCC). Patients and methods Twenty-six patients with non-resectable HCC treated with SBRT were included in this study. Clinical, biochemical and treatment-related parameters were retrospectively collected. S-albumin, s-bilirubin, s-alkaline phosphatase (AP) and s-alanine transaminase (ALAT) at 0, 3, 6, and 12 months after radiotherapy were analyzed. Results Seventeen and nine patients were Child-Pugh class A and B, respectively. The liver was exposed to relatively high radiation doses with mean doses of 1.9-26 Gy. None of the patients developed classic radiotherapy-induced liver disease (RILD), but two patients developed non-classic RILD. Two patients developed grade 3 ascites and no grade 4-5 toxicities were observed. Six patients declined in Child-Pugh class. The s-albumin decreased significantly from a pretreatment median of 37.4-34.36 g/l at three months after SBRT and stabilized thereafter. S-bilirubin, s-AP and s-ALAT did not change significantly over the study period. Conclusion Despite the fact that patients received high radiation dose to the liver, there was only moderate morbidity related to the treatment. The s-albumin decreases over three months after SBRT reflecting minor to moderate hepatic toxicity. S-albumin should be observed in the follow-up of HCC patients treated with SBRT.
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Affiliation(s)
- Constantin Dreher
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany
| | - Katrine I. Høyer
- Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark
| | - Mette Marie Fode
- Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark
| | - Daniel Habermehl
- Department of Radiotherapy and Radiooncology, Klinikum Rechts Der Isar, Munich, Germany
| | - Stephanie E. Combs
- Department of Radiotherapy and Radiooncology, Klinikum Rechts Der Isar, Munich, Germany
| | - Morten Høyer
- Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark
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10
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Radiation induced liver disease: A clinical update. J Egypt Natl Canc Inst 2015; 28:7-11. [PMID: 26300327 DOI: 10.1016/j.jnci.2015.08.001] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 07/26/2015] [Accepted: 08/04/2015] [Indexed: 01/12/2023] Open
Abstract
Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form of liver injury due to radiation. It is one of the most dreaded complications of radiation which prevents radiation dose escalation and re-irradiation for hepatobiliary or upper gastrointestinal malignancies. This complication should be kept in mind whenever a patient is planned for irradiation of these malignancies. Although, incidence of RILD is decreasing due to better knowledge of liver tolerance, improved investigation modalities and modern radiation delivery techniques, treatment options are still limited. In this review article, we have focussed on patho-physiology, risk factors, prevention and management of RILD.
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11
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Safety of redo hepatectomy for colorectal liver metastases after selective interarterial radiation therapy: a case report. Case Rep Surg 2014; 2014:712572. [PMID: 24716079 PMCID: PMC3971541 DOI: 10.1155/2014/712572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 01/19/2014] [Indexed: 11/30/2022] Open
Abstract
Surgical resection is the only potentially curative strategy in the treatment of patients with colorectal liver metastases (CLM). Unfortunately, only about 10%–15% of patients are candidates for resection. Preoperative chemotherapy aims to increase the number of patients that may be eligible for liver resection by downsizing liver metastases. For patients with unresectable, chemotherapy refractory CLM the available treatment options are limited. Selective interarterial radiation therapy (SIRT) is one of the most promising treatment options for this group of patients. Although only a small number of these patients have been reported as becoming candidates for potentially curative hepatic resection following sufficient reduction in the volume of liver metastases, the question arises regarding the safety of liver resection in these patients. We report a case of a patient who presented unresectable liver relapse of CLM after previous right hepatectomy. He underwent SIRT which resulted in downsizing of the liver metastases making the patient candidate for left lateral sectionectomy. He underwent the redo hepatectomy without any complications. To the best of our knowledge, this is the first reported case of redo hepatectomy after SIRT for CLM.
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12
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Cardinale V, De Filippis G, Corsi A, La Penna A, Rossi M, Catalano C, Bianco P, De Santis A, Alvaro D. An isolate alpha-fetoprotein producing gastric cancer liver metastasis emerged in a patient previously affected by radiation induced liver disease. World J Hepatol 2013; 5:398-403. [PMID: 23898374 PMCID: PMC3724969 DOI: 10.4254/wjh.v5.i7.398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Revised: 11/05/2011] [Accepted: 11/14/2012] [Indexed: 02/06/2023] Open
Abstract
We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohistochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.
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Affiliation(s)
- Vincenzo Cardinale
- Vincenzo Cardinale, Domenico Alvaro, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, Italy
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13
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Smits MLJ, van den Hoven AF, Rosenbaum CENM, Zonnenberg BA, Lam MGEH, Nijsen JFW, Koopman M, van den Bosch MAAJ. Clinical and laboratory toxicity after intra-arterial radioembolization with (90)y-microspheres for unresectable liver metastases. PLoS One 2013; 8:e69448. [PMID: 23894481 PMCID: PMC3722288 DOI: 10.1371/journal.pone.0069448] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2012] [Accepted: 06/07/2013] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90)Y-RE). METHODS Patients with liver metastases treated with (90)Y-RE, between February 1(st) 2009 and March 31(st) 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3-4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions). Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP) and overall survival were calculated by Kaplan-Meier analysis. RESULTS A total of 59 patients, with liver metastases from colorectal cancer (n = 30), neuroendocrine tumors (NET) (n = 6) and other primary tumors (n = 23) were included. Clinical toxicity after (90)Y-RE treatment was confined to grade 1-2 events, predominantly post-embolization symptoms. No grade 3-4 clinical toxicity was observed, whereas laboratory toxicity grade 3-4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months. CONCLUSION The risk of severe complications or grade 3-4 clinical toxicity in patients with liver metastases of various primary tumors undergoing (90)Y-RE is low. In contrast, laboratory toxicity grade 3-4 can be expected to occur in more than one-third of patients without any clinical signs of radiation induced liver disease.
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Affiliation(s)
- Maarten L J Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
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Du SS, Zeng ZC, Tang ZY, Zhang ZY, Shi LS, Wu Z, Qiang M, Liu ZS. Regenerative capacity of normal and irradiated liver following partial hepatectomy in rats. Int J Radiat Biol 2010; 85:1114-25. [PMID: 19995237 DOI: 10.3109/09553000903242115] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
PURPOSE To investigate the regenerative capacity and proliferation related to cell cycle modulators in irradiated livers after partial hepatectomy (PH) in rats. METHODS AND MATERIALS Two experimental groups were given a single dose of either 4-Gy or 8-Gy photon radiation to the whole liver following PH. The control group underwent only PH, without irradiation. The liver specimens were analysed for apoptosis, proliferation and cell cycle related genes between 0.5 and 12 days. RESULTS Mean change in weight of the remnant liver in the 8-Gy group was significantly lower than in the control and 4-Gy groups. The apex of proliferating cell nuclear antigen labelling and bromodeoxyuridine incorporation index in two irradiated groups were also apparently lower than that in control group. After PH, transforming growth factor beta-1 (TGFbeta1), and the type II receptor of TGFbeta (TGFbetaR-II), anti-tumour protein 53(p53) and anti-tumour protein21(p21) protein expression in the irradiated livers was higher than in unirradiated ones. Significant apoptosis was noted in 8-Gy group. However, the maximal value of hepatocyte growth factor (HGF) mRNA and protein expression in the irradiated group was suppressed and restoration of liver function was delayed. CONCLUSION Whole liver lower dose irradiation can attenuate regenerative capacity following partial hepatectomy in rats.
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Affiliation(s)
- Shi-Suo Du
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032,China
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