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Morakote W, Adams LC, Ramasamy SK, Spunt SL, Baratto L, Liang T, Daldrup-Link HE. Tyrosine kinase inhibitor therapy in pediatric sarcoma: Prognostic implications of pulmonary metastatic cavitation. Pediatr Blood Cancer 2023; 70:e30629. [PMID: 37580891 PMCID: PMC10947454 DOI: 10.1002/pbc.30629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 07/08/2023] [Accepted: 08/06/2023] [Indexed: 08/16/2023]
Abstract
PURPOSES This study aims to ascertain the prevalence of cavitations in pulmonary metastases among pediatric and young adult patients with sarcoma undergoing tyrosine kinase inhibitor (TKI) therapy, and assess whether cavitation can predict clinical response and survival outcomes. METHODS In a single-center retrospective analysis, we examined chest computed tomography (CT) scans of 17 patients (median age 16 years; age range: 4-25 years) with histopathologically confirmed bone (n = 10) or soft tissue (n = 7) sarcoma who underwent TKI treatment for lung metastases. The interval between TKI initiation and the onset of lung nodule cavitation and tumor regrowth were assessed. The combination of all imaging studies and clinical data served as the reference standard for clinical responses. Progression-free survival (PFS) was compared between patients with cavitating and solid nodules using Kaplan-Meier survival analysis and log-rank test. RESULTS Five out of 17 patients (29%) exhibited cavitation of pulmonary nodules during TKI therapy. The median time from TKI initiation to the first observed cavitation was 79 days (range: 46-261 days). At the time of cavitation, all patients demonstrated stable disease. When the cavities began to fill with solid tumor, 60% (3/5) of patients exhibited progression in other pulmonary nodules. The median PFS for patients with cavitated pulmonary nodules after TKI treatment (6.7 months) was significantly longer compared to patients without cavitated nodules (3.8 months; log-rank p-value = .03). CONCLUSIONS Cavitation of metastatic pulmonary nodules in sarcoma patients undergoing TKI treatment is indicative of non-progressive disease, and significantly correlates with PFS.
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Affiliation(s)
- Wipawee Morakote
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
- Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Lisa C Adams
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
| | - Shakthi K Ramasamy
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
| | - Sheri L Spunt
- Department of Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, California, USA
| | - Lucia Baratto
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
| | - Tie Liang
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
| | - Heike E Daldrup-Link
- Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, Stanford, California, USA
- Department of Pediatrics, Division of Hematology and Oncology, Stanford University, Stanford, California, USA
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Atkins MB, Ascierto PA, Feltquate D, Gulley JL, Johnson DB, Khushalani NI, Sosman J, Yap TA, Kluger H, Sullivan RJ, Tawbi H. Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors with targeted therapies. J Immunother Cancer 2023; 11:e005923. [PMID: 36918225 PMCID: PMC10016252 DOI: 10.1136/jitc-2022-005923] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2022] [Indexed: 03/15/2023] Open
Abstract
Immunotherapy offers deep and durable disease control to some patients, but many tumors do not respond to treatment with single-agent immune checkpoint inhibitors (ICIs). One strategy to enhance responses to immunotherapy is via combinations with signal transduction inhibitors, such as antiangiogenic therapies, which not only directly target cancer cells but also could potentially favorably modulate the tumor immune microenvironment. Combination strategies with ICIs have demonstrated enhanced antitumor activity compared with tumor-targeted or antiangiogenic therapy alone in randomized trials in a variety of solid tumor settings, leading to regulatory approval from the US Food and Drug Administration and agencies in other countries for the treatment of endometrial cancer, kidney cancer, melanoma, and hepatocellular carcinoma. Despite improved survival and response rates for some patients when antiangiogenic or targeted therapies are administered with ICIs, many patients continue to progress after combination treatment and urgently need new strategies to address this manifestation of resistance to immunotherapy. Previously, the Society for Immunotherapy of Cancer (SITC) published consensus definitions for resistance to single-agent anti-PD-(L)1. To provide guidance for clinical trial design and to support analyses of emerging molecular and immune profiling data surrounding mechanisms of resistance to ICI-based combinations, SITC convened a follow-up workshop in 2021 to develop consensus definitions for resistance to multiagent ICI combinations. This manuscript reports the consensus clinical definitions for combinations of anti-PD-(L)1 ICIs and targeted therapies. Definitions for resistance to ICIs in combination with chemotherapy and with other ICIs will be published in companion volumes to this paper.
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Affiliation(s)
| | - Paolo A Ascierto
- Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
| | | | | | | | | | | | - Timonthy A Yap
- University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | | | - Hussein Tawbi
- University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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3
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Fadhel MN, Hysi E, Strohm EM, Kolios MC. Optical and photoacoustic radiofrequency spectroscopic analysis for detecting red blood cell death. JOURNAL OF BIOPHOTONICS 2019; 12:e201800431. [PMID: 31050867 DOI: 10.1002/jbio.201800431] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 04/30/2019] [Accepted: 05/02/2019] [Indexed: 05/15/2023]
Abstract
Under stress, red blood cells (RBCs) undergo programmed cell death (eryptosis). One of the signaling molecules for eryptosis, sphingomyelinase (SMase), plays an important role in monitoring the efficacy of vascular targeted cancer therapy. The high optical absorption of erythrocytes coupled with the changes of eryptotic RBCs makes RBCs ideal targets for the photoacoustic (PA) detection and characterization of vascular treatments. In this work, experiments characterizing eryptosis were performed: PA detection of high frequencies (>100 MHz) that enabled analysis at the single-cell level and of low frequencies (21 MHz) that enabled analysis at the RBC ensemble level. Ultrasound spectral analysis was performed on control and SMase-treated RBCs. Spectral unmixing was applied to quantify methemoglobin production as a by-product of RBC death. Validation was performed using a blood gas analyzer and optical spectrometry. Our results indicate that PA radiofrequency spectra could be used to differentiate the biochemically induced morphological changes as RBCs lose their native biconcave shape, and release hemoglobin into the surroundings. Spectral unmixing revealed a 7% increase in methemoglobin content for SMase-treated samples due to the oxidative stress on the RBCs. These findings suggest that PA spectral analysis of RBC death can potentially serve as a biomarker of the efficacy of vascular targeted cancer therapies.
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Affiliation(s)
- Muhannad N Fadhel
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada
| | - Eno Hysi
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada
| | - Eric M Strohm
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada
- Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada
| | - Michael C Kolios
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology (iBEST), Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada
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4
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Abstract
Renal cell carcinoma (RCC) exhibits a diverse and heterogeneous disease spectrum, but insight into its molecular biology has provided an improved understanding of potential risk factors, oncologic behavior, and imaging features. Computed tomography (CT) and MR imaging may allow the identification and preoperative subtyping of RCC and assessment of a response to various therapies. Active surveillance is a viable management option in some patients and has provided further insight into the natural history of RCC, including the favorable prognosis of cystic neoplasms. This article reviews CT and MR imaging in RCC and the role of screening in selected high-risk populations.
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Affiliation(s)
- Alberto Diaz de Leon
- Department of Radiology, University of Texas Southwestern Medical Center, 2201 Inwood Road, 2nd Floor, Suite 202, Dallas, TX 75390-9085, USA
| | - Ivan Pedrosa
- Department of Radiology, University of Texas Southwestern Medical Center, 2201 Inwood Road, 2nd Floor, Suite 202, Dallas, TX 75390-9085, USA.
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5
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Lee Y, Lee SS, Cheong H, Lee CK, Kim N, Son WC, Hong SM. Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models. Acta Radiol 2017; 58:1045-1053. [PMID: 28273738 DOI: 10.1177/0284185116683576] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Background With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx). IVIM imaging was performed using 10 b-values (0-900 s/mm2). The apparent diffusion coefficient (ADC), diffusion coefficient ( D), and perfusion fraction ( f) were measured for whole tumors and tumor periphery. Changes between baseline and post-treatment parameters ( Δ ADC, Δ D, and Δ f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death. Results The post-treatment f and Δ f for tumor periphery were significantly higher in control group, followed by 5 mg-Tx and 30 mg-Tx ( P < 0.001). MVD showed significant positive correlation with post-treatment f ( r = 0.584, P = 0.003) and negative correlation with D ( r = -0.495, P = 0.014) for tumor periphery, while no parameter showed significant correlation with area of tumor cell death. Conclusion The f is significantly correlated with MVD of HCC, and could potentially be used to evaluate the anti-angiogenic effects of sorafenib.
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Affiliation(s)
- Yedaun Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
- Current address: Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyunhee Cheong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Chang Kyung Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Namkug Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Woo-Chan Son
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma. CONTRAST MEDIA & MOLECULAR IMAGING 2017; 2017:9265098. [PMID: 29097941 PMCID: PMC5612611 DOI: 10.1155/2017/9265098] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 05/25/2017] [Indexed: 12/11/2022]
Abstract
We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI) and mean vessel density imaging (Q) in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC). Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS) and Q were serially measured and compared between the treated (n = 15) and control groups (n = 15). Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05). Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669) and increased at 14 and 21 days (P < 0.05), while Q significantly declined at 7 days (P = 0.028) and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD) (r = 0.753, P < 0.001), and ITSS correlated well with MVD (r = 0.742, P = 0.002) after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.
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Yin Q, Hung SC, Wang L, Lin W, Fielding JR, Rathmell WK, Khandani AH, Woods ME, Milowsky MI, Brooks SA, Wallen EM, Shen D. Associations between Tumor Vascularity, Vascular Endothelial Growth Factor Expression and PET/MRI Radiomic Signatures in Primary Clear-Cell-Renal-Cell-Carcinoma: Proof-of-Concept Study. Sci Rep 2017; 7:43356. [PMID: 28256615 PMCID: PMC5335708 DOI: 10.1038/srep43356] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Accepted: 01/23/2017] [Indexed: 12/25/2022] Open
Abstract
Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.
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Affiliation(s)
- Qingbo Yin
- College of Information Science and Technology, Dalian Maritime University, Dalian, 116023, China.,Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Sheng-Che Hung
- Department of Radiology, Taipei Veterans General Hospital, Taipei, 11217, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.,Department of Biomedical Imaging and Radiological Sciences, School of Biomedical Science of Engineering, National Yang-Ming University, Taipei, 11221, Taiwan
| | - Li Wang
- Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Weili Lin
- Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Julia R Fielding
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - W Kimryn Rathmell
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.,Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN 37232, USA
| | - Amir H Khandani
- Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Michael E Woods
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Matthew I Milowsky
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Samira A Brooks
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Eric M Wallen
- Department of Urology, University of North Carolina, Chapel Hill, NC 27599, USA
| | - Dinggang Shen
- Department of Radiology, University of North Carolina, Chapel Hill, NC 27599, USA.,Department of Brain and Cognitive Engineering, Korea University, Seoul 02841, Republic of Korea
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8
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Patchett N, Furlan A, Marsh JW. Decrease in tumor enhancement on contrast-enhanced CT is associated with improved survival in patients with hepatocellular carcinoma treated with Sorafenib. Jpn J Clin Oncol 2016; 46:839-44. [PMID: 27317737 DOI: 10.1093/jjco/hyw078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 05/23/2016] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND This study investigates whether changes in arterial enhancement of hepatocellular carcinoma (HCC) on contrast-enhanced CT in patients treated with Sorafenib predicts overall survival. METHODS Thirty-seven HCC patients treated with Sorafenib were identified retrospectively. Up to two target liver lesions were measured on baseline and follow-up contrast-enhanced CT scans. Patients were stratified by whether arterial enhancement decreased by at least 15% and hazard ratio was calculated for all-cause mortality. Patients were then classified as progressive disease, stable disease or partial response using both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and a novel system of enhancement-based response criteria we modeled on mRECIST, but substituting change in arterial enhancement for longest enhancing diameter as the primary measure of tumor response. This response stratification was assessed using survival analysis. RESULTS Patients with a 15% decrease in arterial enhancement on follow-up contrast-enhanced CT had median overall survival of 1022 days versus 189 days in those without; this corresponded to a significant decrease in risk of all-cause mortality (hazard ratio 0.34; P = 0.04). Response groups created using the enhancement-based criteria showed significant differences in overall survival (P < 0.001) and all response groups were significantly separated from each other on a pair-wise basis. CONCLUSIONS Decrease in arterial tumor enhancement on follow-up contrast-enhanced CT by at least 15% was associated with improved overall survival in this small sample of HCC patients treated with Sorafenib and shows promise as a possible clinical measure of tumor response in this population.
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Affiliation(s)
| | | | - J Wallis Marsh
- University of Pittsburgh Medical Center, Department of Surgery
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9
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Kaufmann S, Schulze M, Spira D, Horger M. Modern multimodality diagnosis of portal vein infiltration in hepatocellular carcinoma and expected changes during current therapies. Acta Radiol 2015; 56:1283-92. [PMID: 25348478 DOI: 10.1177/0284185114556305] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2013] [Accepted: 09/22/2014] [Indexed: 12/15/2022]
Abstract
Diagnosis of malignant portal vein infiltration and especially differentiation from bland thrombosis is challenging for most imaging techniques. The use of contrast-enhanced real-time modern imaging modalities like contrast-enhanced ultrasound (CEUS), volume perfusion CT (VPCT), or dynamic contrast-enhanced MRI (DCE-MRI) with dedicated postprocessing tools provides additional support in difficult cases and is therefore recommended.The purpose of this review is to present a practical overview of strengths and limitations of modern imaging techniques in the diagnosis of malignant infiltration of the portal vein by hepatocellular carcinoma and to describe subsequent changes during therapy.
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Affiliation(s)
- Sascha Kaufmann
- Department of Radiology, Diagnostic and Interventional Radiology, Eberhard-Karls-University, Tübingen, Germany
| | - Maximilian Schulze
- Department of Radiology, Diagnostic and Interventional Radiology, Eberhard-Karls-University, Tübingen, Germany
| | - Daniel Spira
- Department of Radiology, Diagnostic and Interventional Radiology, Eberhard-Karls-University, Tübingen, Germany
| | - Marius Horger
- Department of Radiology, Diagnostic and Interventional Radiology, Eberhard-Karls-University, Tübingen, Germany
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10
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Das CJ, Thingujam U, Panda A, Sharma S, Gupta AK. Perfusion computed tomography in renal cell carcinoma. World J Radiol 2015; 7:170-179. [PMID: 26217456 PMCID: PMC4506935 DOI: 10.4329/wjr.v7.i7.170] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 03/30/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
Various imaging modalities are available for the diagnosis, staging and response evaluation of patients with renal cell carcinoma (RCC). While contrast enhanced computed tomography (CT) is used as the standard of imaging for size, morphological evaluation and response assessment in RCC, a new functional imaging technique like perfusion CT (pCT), goes down to the molecular level and provides new perspectives in imaging of RCC. pCT depicts regional tumor perfusion and vascular permeability which are indirect parameters of tumor angiogenesis and thereby provides vital information regarding tumor microenvironment. Also response evaluation using pCT may predate the size criteria used in Response Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier following tissue kinase inhibitors before any actual change in size. This may potentially help in predicting prognosis, better selection of therapy and more accurate and better response evaluation in patients with RCC. This article describes the techniques and role of pCT in staging and response assessment in patients with RCCs.
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12
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Choi JI, Imagawa DK, Bhosale P, Bhargava P, Tirkes T, Seery TE, Lall C. Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib. Clin Mol Hepatol 2015; 20:218-22. [PMID: 25032190 PMCID: PMC4099339 DOI: 10.3350/cmh.2014.20.2.218] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
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Affiliation(s)
- Joon-Il Choi
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea, Seoul, Korea. ; Department of Radiological Sciences, University of California, Irvine, Orange, CA, USA
| | - David K Imagawa
- Department of Hepatobiliary Surgery, University of California, Irvine, Orange, CA, USA
| | - Priya Bhosale
- Department of Radiological Sciences, MD Anderson Medical Center, Houston, TX, USA
| | - Puneet Bhargava
- Department of Radiology, VA Puget Sound, University of Washington, Seattle, WA, USA
| | - Temel Tirkes
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Tara E Seery
- Department of Oncology, University of California, Irvine, Orange, CA, USA
| | - Chandana Lall
- Department of Radiological Sciences, University of California, Irvine, Orange, CA, USA
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13
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Brufau BP, Cerqueda CS, Villalba LB, Izquierdo RS, González BM, Molina CN. Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT. Radiographics 2014; 33:1691-716. [PMID: 24108558 DOI: 10.1148/rg.336125110] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Recent advances in treatment of metastatic renal cell carcinoma (RCC), such as new molecular therapies that use novel antiangiogenic agents, have led to revision of the most frequently used guideline to evaluate tumor response to therapy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of newer antiangiogenic therapies is more cytostatic than cytotoxic, which leads to disease stabilization rather than to tumor regression. This change in tumor response makes RECIST 1.1--a system whose criteria are based exclusively on tumor size--inadequate to discriminate patients with early tumor progression from those with more progression-free disease and prolonged survival. New criteria such as changes in attenuation, morphology, and structure, as seen at contrast-enhanced multidetector computed tomography (CT), are being incorporated into new classifications used to assess response of metastatic RCC to antiangiogenic therapies. The new classifications provide better assessments of tumor response to the new therapies, but they have some limitations. The authors provide a practical review of these systems--the Choi, modified Choi, and Morphology, Attenuation, Size, and Structure (MASS) criteria--by explaining their differences and limitations that may influence the feasibility and reproducibility of these classifications. The authors review the use of multidetector CT in the detection of metastatic RCC and the different appearances and locations of these lesions. They also provide an overview of the new antiangiogenic therapies and their mechanisms of action and a brief introduction to functional imaging techniques. Functional imaging techniques, especially dynamic contrast-enhanced CT, seem promising for assessing response of metastatic RCC to treatment. Nonetheless, further studies are needed before functional imaging can be used in routine clinical practice.
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Affiliation(s)
- Blanca Paño Brufau
- CDIC and ICMHO, Hospital Clínic de Barcelona, C/Villarroel n° 170, 08036 Barcelona, Spain
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Bargellini I, Scionti A, Mismas V, Masi G, Vivaldi C, Bartolozzi C, Sacco R. Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward? Oncology 2014; 86:191-8. [PMID: 24800837 DOI: 10.1159/000358599] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 12/20/2013] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. METHODS The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. RESULTS The response criteria and volume measurements were reproducible (k > 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios >1.1 (p = 0.04). CONCLUSIONS Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO.
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Affiliation(s)
- Irene Bargellini
- Department of Diagnostic and Interventional Radiology, Pisa University Hospital, Pisa, Italy
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15
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León L, García-Figueiras R, García-Figueras R, Suárez C, Arjonilla A, Puente J, Vargas B, Méndez Vidal MJ, Sebastiá C. Recommendations for the clinical and radiological evaluation of response to treatment in metastatic renal cell cancer. Target Oncol 2013; 9:9-24. [PMID: 24338498 DOI: 10.1007/s11523-013-0304-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 11/28/2013] [Indexed: 12/21/2022]
Abstract
The evaluation of response to treatment is a critical step for determining the effectiveness of oncology drugs. Targeted therapies such as tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are active drugs in patients with metastatic renal cell carcinoma (mRCC). However, treatment with this type of drugs may not result in significant reductions in tumor size, so standard evaluation criteria based on tumor size, such as Response Evaluation Criteria in Solid Tumors (RECIST), may be inappropriate for evaluating response to treatment in patients with mRCC. In fact, targeted therapies apparently yield low response rates that do not reflect increased disease control they may cause and, consequently, the benefit in terms of time to progression. To improve the clinical and radiological evaluation of response to treatment in patients with mRCC treated with targeted drugs, a group of 32 experts in this field have reviewed different aspects related to this issue and have put together a series of recommendations with the intention of providing guidance to clinicians on this matter.
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Affiliation(s)
- Luís León
- Medical Oncology Department, Complejo Hospitalario Universitario de Santiago, A Coruña, Spain,
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16
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Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging: response assessment after treatment with sorafenib: preliminary results. Radiol Med 2013; 119:215-21. [DOI: 10.1007/s11547-013-0332-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2012] [Accepted: 04/23/2013] [Indexed: 12/15/2022]
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17
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Procopio G, Verzoni E, Bracarda S, Ricci S, Sacco C, Ridolfi L, Porta C, Miceli R, Zilembo N, Bajetta E. Overall survival for sorafenib plus interleukin-2 compared with sorafenib alone in metastatic renal cell carcinoma (mRCC): final results of the ROSORC trial. Ann Oncol 2013; 24:2967-71. [PMID: 24063860 DOI: 10.1093/annonc/mdt375] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The ROSORC trial, a randomised, phase II trial comparing sorafenib plus interleukin (IL-2) versus sorafenib alone as first-line treatment of metastatic renal cell carcinoma (mRCC) failed to demonstrate differences in progression-free survival (PFS). Updated overall survival (OS) results are reported. PATIENTS AND METHODS In this study, 128 patients were randomised to receive sorafenib 400 mg twice daily plus subcutaneous IL-2 4.5 million international units (MIU) five times per week for 6 weeks every 8 weeks (arm A) or sorafenib alone (arm B). OS was estimated with the Kaplan-Meier method and compared with the two-sided log-rank test. RESULTS After a median follow-up of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in arms A and B, respectively (P = 0.667). The 5-year OS was 26.3% [95% confidence interval (CI) 15.9-43.5) and 23.1% (95% CI 13.2-40.5) for the combination- and single-agent arm, respectively. Most of the patients who were refractory to first-line treatment were subsequently treated with different targeted agents; they had a median survival greater than expected. CONCLUSIONS This outcome suggests a synergistic effect of the subsequent therapies following sorafenib failure. CLINICALTRIALSGOV IDENTIFIER NCT00609401.
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Affiliation(s)
- G Procopio
- Department of Medical Oncology, Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
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18
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Peungjesada S, Chuang HH, Prasad SR, Choi H, Loyer EM, Bronstein Y. Evaluation of cancer treatment in the abdomen: Trends and advances. World J Radiol 2013; 5:126-42. [PMID: 23671749 PMCID: PMC3650203 DOI: 10.4329/wjr.v5.i3.126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Revised: 01/24/2013] [Accepted: 01/31/2013] [Indexed: 02/06/2023] Open
Abstract
Response evaluation in Oncology has relied primarily on change in tumor size. Inconsistent results in the prediction of clinical outcome when size based criteria are used and the increasing role of targeted and loco-regional therapies have led to the development of new methods of response evaluation that are unrelated to change in tumor size. The goals of this review are to expose briefly the size based criteria and to present the non-size based approaches that are currently applicable in the clinical setting. Other paths that are still being explored are not discussed in details.
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19
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Abstract
Based on recent clinical practice guidelines, imaging is largely replacing pathology as the preferred diagnostic method for determination of hepatocellular carcinoma (HCC). A variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography, are currently used to examine patients with chronic liver disease and suspected HCC. Advancements in imaging techniques such as perfusion imaging, diffusion imaging, and elastography along with the development of new contrast media will further improve the ability to detect and characterize HCC. Early diagnosis of HCC is essential for prompt treatment, which may in turn improve prognosis. Considering the process of hepatocarcinogenesis, it is important to evaluate sequential changes via imaging which would help to differentiate HCC from premalignant or benign lesions. Recent innovations including multiphasic examinations, high-resolution imaging, and the increased functional capabilities available with contrast-enhanced US, multidetector row CT, and MRI have raised the standards for HCC diagnosis. Although hemodynamic features of nodules in the cirrhotic liver remain the main diagnostic criterion, newly developed cellspecific contrast agents have shown great possibilities for improved HCC diagnosis and may overcome the diagnostic dilemma associated with small or borderline hepatocellular lesions. In the 20th century paradigm of medical imaging, radiological diagnosis was based on morphological characteristics, but in the 21st century, a paradigm shift to include biomedical, physiological, functional, and genetic imaging is needed. A multidisciplinary team approach is necessary to foster an integrated approach to HCC imaging. By developing and combining new imaging modalities, all phases of HCC patient care, including screening, diagnosis, treatment, and therapy, can be dramatically improved.
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Affiliation(s)
| | - Byung Ihn Choi
- *Byung Ihn Choi, MD, Department of Radiology, Seoul National University Hospital, 101 Daehakro, Jongno-gu, Seoul 110-744 (Korea), Tel. +82 2 2072 2515, E-Mail
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20
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Tinkle CL, Haas-Kogan D. Hepatocellular carcinoma: natural history, current management, and emerging tools. Biologics 2012; 6:207-19. [PMID: 22904613 PMCID: PMC3421475 DOI: 10.2147/btt.s23907] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery – either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the diagnosis and treatment of this highly lethal cancer.
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Affiliation(s)
- Christopher L Tinkle
- Department of Radiation Oncology, University of California, San Francisco, CA, USA
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21
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Lee JM, Yoon JH, Joo I, Woo HS. Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma. Liver Cancer 2012; 1:22-40. [PMID: 24159569 PMCID: PMC3747553 DOI: 10.1159/000339018] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities.
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Affiliation(s)
| | - Jeong-Hee Yoon
- *Jeong Min Lee, MD, Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744 (South Korea), Tel. +82 2 2072 3154, E-Mail
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22
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Fabries P, Pauleau G, Brardjanian S, Artéaga C, Guisset M, Coton T. [Metastatic adrenal necrosis under sorafenib treatment for hepatocellular carcinoma]. Presse Med 2012; 42:235-7. [PMID: 22425476 DOI: 10.1016/j.lpm.2012.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 02/02/2012] [Accepted: 02/06/2012] [Indexed: 11/27/2022] Open
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23
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Hollebecque A, Cattan S, Romano O, Sergent G, Mourad A, Louvet A, Dharancy S, Boleslawski E, Truant S, Pruvot FR, Hebbar M, Ernst O, Mathurin P. Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score. Aliment Pharmacol Ther 2011; 34:1193-201. [PMID: 21958438 DOI: 10.1111/j.1365-2036.2011.04860.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Sorafenib increases median survival and time to radiological progression in patients with advanced hepatocellular carcinoma, but its benefit for Child-Pugh B patients remains uncertain. AIM To evaluate the safety and efficacy of sorafenib in real-life clinical practice conditions and to assess the influence of Child-Pugh class B on safety and efficacy. METHODS All patients treated with sorafenib for advanced hepatocellular carcinoma in our institution were included prospectively. Adverse events, overall survival and time to progression were recorded. A case control study was performed to compare outcome of patients with comparable stages of hepatocellular carcinoma, but a different Child-Pugh class. RESULTS From March 2007 to May 2009, 120 patients were included. Overall survival was 11.1 months, Child-Pugh A patients (n=100) had significantly higher median survival than Child-Pugh B patients (n=20) (13 vs. 4.5 months, P=0.0008). In multivariate analysis, Child-Pugh class B, α-fetoprotein level and total size of lesions were independent predictive factors of death. Patients with radiological progression in the first 3 months had shorter median survival (5.4 vs. 17.4 months). In a case control study, time to symptomatic progression (2.5 vs. 3.6 months), frequency of adverse events and discontinuation of sorafenib were not correlated with Child-Pugh class. CONCLUSIONS Patients with advanced hepatocellular carcinoma treated with sorafenib had a median survival of 11 months. Sorafenib therapy must be considered with caution in Child-Pugh B patients due to their poor survival. Radiological assessment of tumour progression at an early stage may be advantageous when tailoring sorafenib therapy.
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Affiliation(s)
- A Hollebecque
- Service d'Hépato-Gastroentérologie, CHRU Lille, France
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24
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Abstract
Surgical hepatectomy or liver transplantation are considered as curative treatment modalities for hepatocellular carcinoma (HCC). However, many patients are not surgical candidates at the time of diagnosis. Great improvements in locoregional therapies including local ablative therapy [radiofrequency (RF) ablation or ethanol ablation] and transarterial techniques (transarterial embolization or transarterial radioembolization) have made possible local control of HCC. For unresectable HCC, a targeted therapy with sorafenib may improve survival. Unlike treatment of other oncologic tumor, the locoregional therapies are mainstay in the treatment of HCC. Therefore, the application of classical criteria such as the World Health Organization (WHO) guideline may not be suitable for accurate treatment response assessment of locoregional therapies or targeted therapy of HCC. An understanding of the imaging features of post-treatment imaging after various treatment modalities for HCC is crucial for treatment response assessment and for determining further therapy. In this article, we review the role of various imaging modalities in assessing treatment response of locoregional therapies and the targeted molecular therapy.
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25
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Fartoux L, Decaens T. Contribution of biomarkers and imaging in the management of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2011; 35 Suppl 1:S21-30. [PMID: 21742297 DOI: 10.1016/s2210-7401(11)70004-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most frequent malignant tumour of the liver. HCC prognosis is dependent on the determination of the tumour stage by conventional imaging and early screening. However, patient survival can vary with the same tumour stage. Biomarkers thus have a role in providing an earlier diagnosis, better prognosis classification before treatment and classification prognosis during treatment. In this review article, we will provide a successive, detailed description of the serum, pathological, molecular and imaging markers of HCC.
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Affiliation(s)
- Laetitia Fartoux
- Department of Hepatology, Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine 75571 Paris Cedex 12, Paris, France.
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26
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van der Veldt AAM, Meijerink MR, van den Eertwegh AJM, Boven E. Targeted therapies in renal cell cancer: recent developments in imaging. Target Oncol 2010; 5:95-112. [PMID: 20625845 PMCID: PMC2929340 DOI: 10.1007/s11523-010-0146-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2010] [Accepted: 06/24/2010] [Indexed: 01/14/2023]
Abstract
Targeted therapy has significantly improved the perspectives of patients with metastatic renal cell cancer (mRCC). Frequently, these new molecules cause disease stabilization rather than substantial tumor regression. As treatment options expand with the growing number of targeted agents, there is an increasing need for surrogate markers to early assess tumor response. Here, we review the currently available imaging techniques and response evaluation criteria for the assessment of tumor response in mRCC patients. For computed tomography (CT), different criteria are discussed including the Response Evaluation Criteria in Solid Tumors (RECIST), the Choi criteria, the modified Choi criteria, and the size and attenuation CT (SACT) criteria. Functional imaging modalities are discussed, such as dynamic contrast-enhanced CT (DCE-CT), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), dynamic contrast-enhanced ultrasonography (DCE-US), and positron emission tomography (PET).
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Affiliation(s)
- Astrid A M van der Veldt
- Department of Nuclear Medicine & PET Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
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27
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Abstract
The increased use of abdominal imaging techniques for a variety of indications has contributed to more-frequent detection of renal cell carcinoma (RCC). Ultrasonography has been used to characterize the solid versus cystic nature of renal masses. This modality has limitations, however, in further characterization of solid tumors and in staging of malignancy, although contrast-enhanced ultrasonography has shown promise. Cross-sectional imaging with multiplanar reconstruction capability via CT or MRI has become the standard-bearer in the diagnosis, staging and surveillance of renal cancers. The use of specific protocols and the exploitation of different imaging characteristics of RCC subtypes, including variations in contrast agent timing, MRI weighting and digital subtraction, have contributed to this diagnostic capability. Cystic renal masses are a special case, evaluation of which can require multiple imaging modalities. Rigorous evaluation of these lesions can provide information that is crucial to prediction of the likelihood of malignancy. Such imaging is not without risk, however, as radiation from frequent CT imaging has been implicated in the development of secondary malignancies, and contrast agents for CT and MRI can pose risks, particularly in patients with compromised renal function.
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28
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Imaging of advanced renal cell carcinoma. World J Urol 2010; 28:253-61. [PMID: 20458484 DOI: 10.1007/s00345-010-0557-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2010] [Accepted: 04/11/2010] [Indexed: 10/19/2022] Open
Abstract
OBJECTIVES To describe current radiological cross-sectional imaging in the detection and staging of advanced renal cell carcinoma (RCC), defined here as RCC reaching beyond the renal capsule, whether by immediate extension or by metastasis. METHODS Review and summary of current radiological and urological literature, including original articles and reviews, retrieved from the medical data base "PubMed". RESULTS Multi-detector-row computed tomography (MDCT) shows a sensitivity of up to 100% and specificity of about 90% for retroperitoneal disease, venous tumour thrombus, and metastasis, but limited accuracy for lymphadenopathy in RCC. Magnetic resonance imaging (MRI) is applied as a problem-solving modality, with particular strength in imaging metastasis to brain and bone. However, dynamic, contrast-enhanced- (DCE-) and arterial-spin-labelling (ASL-) MRI may help to monitor early response to angiogenesis inhibitor drugs. Ultrasonography (US) shows limited capability of identifying retroperitoneal disease, venous tumour thrombus extension, and metastasis. Positron Emission Tomography with 18-fluoro-desoxy-glucose (FDG-PET) demonstrates modest accuracy for metastasis of RCC, with positive studies being suspicious, while negative studies cannot reliably exclude disease. CONCLUSIONS MDCT represents the diagnostic mainstay for the detection and staging of RCC. In the wake of new systemic therapies for advanced RCC, including angiogenesis inhibitor drugs, monitoring treatment response may become a new task for cross-sectional imaging.
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