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      Quantitative Pretreatment CT Parameters as Predictors of Tumor Response of Neuroendocrine Tumor Liver Metastasis to Transcatheter Arterial Bland Embolization

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          Abstract

          Purpose: To assess whether parameters on preprocedural CT can be utilized to predict the response of NETLM to transcatheter arterial bland embolization (TAE). Methods: We retrospectively reviewed 135 target lesions from 48 NETLM patients who underwent TAE and with complete preprocedural multiphasic CT. Parameters on preprocedural CT including the longest diameter, mean attenuation value in nonenhanced, arterial, and portal-venous phases were collected from each target lesion. Radiological responses were assessed according to RECIST 1.1. The parameters of responder lesions and nonresponder lesions were compared. Arterial enhancement index (AEI) and portal-venous enhancement index (PEI) were calculated. The predictive function of AEI and PEI on tumor response was analyzed by receiver operating characteristic (ROC) curve. Results: A total of 72.6% target lesions had a partial response. For patients, the objective response rate was 72.9%. Mean attenuation values of responder lesions were significantly higher than nonresponder lesions in both arterial and portal-venous phases (105.36 ± 37.24 vs. 76.01 ± 19.19, p < 0.001; 96.61 ± 24.04 vs. 82.12 ± 21.37, p = 0.002). ROC curve showed that both AEI and PEI were effective in predicting tumor response (area under the curve [AUC] 0.757, p < 0.001; AUC 0.655, p = 0.005). Conclusion: AEI and PEI, parameters from evaluation of CT pretreatment attenuation of NETLMs, could predict response to TAE treatment.

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          Most cited references 17

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          Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

          Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).
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            Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease.

            Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. A novel classification of LM from NET was established based on their localization and presentation. From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76.4, 63.9 and 46.5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III. The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome.
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              Therapeutic strategies for neuroendocrine liver metastases.

              Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2020
                July 2020
                22 October 2019
                : 110
                : 7-8
                : 697-704
                Affiliations
                aDepartment of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
                bDepartment of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
                cDepartment of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
                dDepartment of Interventional Therapy, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
                eDepartment of Interventional Radiology, General Hospital of Yongmei Group, Yongcheng, China
                Author notes
                *Yu Wang, Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Yuexiu, Guangzhou 510080 (China), E-Mail wyfishking@hotmail.com, , Jie Chen, Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Yuexiu, Guangzhou 510080 (China), E-Mail chen0jie@hotmail.com
                Article
                504257 Neuroendocrinology 2020;110:697–704
                10.1159/000504257
                31639795
                © 2019 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 4, Pages: 8
                Categories
                Research Article

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