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      Current update on imaging for pancreatic neuroendocrine neoplasms

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          Abstract

          Pancreatic neuroendocrine neoplasms (panNEN) are a heterogeneous group of tumors with differing pathological, genetic, and clinical features. Based on clinical findings, they may be categorized into functioning and nonfunctioning tumors. Adoption of the 2017 World Health Organization classification system, particularly its differentiation between grade 3, well-differentiated pancreatic neuroendocrine tumors (panNET) and grade 3, poorly-differentiated pancreatic neuroendocrine carcinomas (panNEC) has emphasized the role imaging plays in characterizing these lesions. Endoscopic ultrasound can help obtain biopsy specimen and assess tumor margins and local spread. Enhancement patterns on computed tomography (CT) and magnetic resonance imaging (MRI) may be used to classify panNEN. Contrast enhanced MRI and diffusion-weighted imaging have been reported to be useful for characterization of panNEN and quantifying metastatic burden. Current and emerging radiotracers have broadened the utility of functional imaging in evaluating panNEN. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT and somatostatin receptor imaging such as Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid–octreotate PET/CT may be useful for improved identification of panNEN in comparison to anatomic modalities. These new techniques can also play a direct role in optimizing the selection of treatment for individuals and predicting tumor response based on somatostatin receptor expression. In addition, emerging methods of radiomics such as texture analysis may be a potential tool for staging and outcome prediction in panNEN, however further investigation is required before clinical implementation.

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          Most cited references76

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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 with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival.

            Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients. Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients. Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis. Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
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              Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

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                Author and article information

                Contributors
                Journal
                World J Clin Oncol
                WJCO
                World Journal of Clinical Oncology
                Baishideng Publishing Group Inc
                2218-4333
                24 October 2021
                24 October 2021
                : 12
                : 10
                : 897-911
                Affiliations
                Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ 85259, United States
                Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
                Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
                Department of Diagnostic Radiology, Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. dganeshan@ 123456mdanderson.org
                Author notes

                Author contributions: Segaran N drafted the review article and contributed to the design of the manuscript; Devine C contributed to the design of the manuscript and edited the draft; Wang M contributed to manuscript design and edited the manuscript; Ganeshan D designed the structure of the overall manuscript and made critical revisions related to important intellectual content of the manuscript; all authors approved the final version of the manuscript.

                Corresponding author: Dhakshinamoorthy Ganeshan, MD, Associate Professor, Department of Diagnostic Radiology, Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1473, Houston, TX 77030, United States. dganeshan@ 123456mdanderson.org

                Article
                jWJCO.v12.i10.pg897
                10.5306/wjco.v12.i10.897
                8546658
                34733612
                6f40d9a8-e72b-40cd-a898-797fc7c72031
                ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 31 March 2021
                : 21 June 2021
                : 27 August 2021
                Categories
                Minireviews

                pancreatic neuroendocrine neoplasms,computed tomography,ultrasound,positron emission tomography,magnetic resonance imaging,peptide receptor radionuclide therapy

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