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1
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Weber M, Telli T, Kersting D, Seifert R. Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors. Cancers (Basel) 2023; 15:3581. [PMID: 37509242 PMCID: PMC10377105 DOI: 10.3390/cancers15143581] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/30/2023] Open
Abstract
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
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Affiliation(s)
- Manuel Weber
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Tugce Telli
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - David Kersting
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Robert Seifert
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
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2
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Piscopo L, Zampella E, Pellegrino S, Volpe F, Nappi C, Gaudieri V, Fonti R, Vecchio SD, Cuocolo A, Klain M. Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:3483. [PMID: 37444593 DOI: 10.3390/cancers15133483] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/23/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023] Open
Abstract
Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs. The theragnostic approach is able to combine diagnosis and therapy by the identification of a molecular target that can be diagnosed and treated with the same radiolabeled compound. During the last years, advances in functional imaging with the introduction of somatostatin analogs and peptide receptor radionuclide therapy, have improved the diagnosis and treatment of GEP-NENs. Moreover, PET/CT imaging with 18F-FDG represents a complementary tool for prognostic evaluation of patients with GEP-NENs. In the field of personalized medicine, the theragnostic approach has emerged as a promising tool in diagnosis and management of patients with GEP-NENs. The aim of this review is to summarize the current evidence on diagnosis and management of patients with GEP-NENs, focusing on the theragnostic approach.
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Affiliation(s)
- Leandra Piscopo
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Emilia Zampella
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Sara Pellegrino
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Fabio Volpe
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Carmela Nappi
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Valeria Gaudieri
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Rosa Fonti
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Silvana Del Vecchio
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Alberto Cuocolo
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
| | - Michele Klain
- Department of Advanced Biomedical Sciences, University of Naples, Federico II, 80131 Naples, Italy
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Prosperi D, Gentiloni Silveri G, Panzuto F, Faggiano A, Russo VM, Caruso D, Polici M, Lauri C, Filice A, Laghi A, Signore A. Nuclear Medicine and Radiological Imaging of Pancreatic Neuroendocrine Neoplasms: A Multidisciplinary Update. J Clin Med 2022; 11:jcm11226836. [PMID: 36431313 PMCID: PMC9694730 DOI: 10.3390/jcm11226836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are part of a large family of tumors arising from the neuroendocrine system. PanNENs show low-intermediate tumor grade and generally high somatostatin receptor (SSTR) expression. Therefore, panNENs benefit from functional imaging with 68Ga-somatostatin analogues (SSA) for diagnosis, staging, and treatment choice in parallel with morphological imaging. This narrative review aims to present conventional imaging techniques and new perspectives in the management of panNENs, providing the clinicians with useful insight for clinical practice. The 68Ga-SSA PET/CT is the most widely used in panNENs, not only fr diagnosis and staging purpose but also to characterize the biology of the tumor and its responsiveness to SSAs. On the contrary, the 18F-Fluordeoxiglucose (FDG) PET/CT is not employed systematically in all panNEN patients, being generally preferred in G2-G3, to predict aggressiveness and progression rate. The combination of 68Ga-SSA PET/CT and 18F-FDG PET/CT can finally suggest the best therapeutic strategy. Other radiopharmaceuticals are 68Ga-exendin-4 in case of insulinomas and 18F-dopamine (DOPA), which can be helpful in SSTR-negative tumors. New promising but still-under-investigation radiopharmaceuticals include radiolabeled SSTR antagonists and 18F-SSAs. Conventional imaging includes contrast enhanced CT and multiparametric MRI. There are now enriched by radiomics, a new non-invasive imaging approach, very promising to early predict tumor response or progression.
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Affiliation(s)
- Daniela Prosperi
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Guido Gentiloni Silveri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Department of Medical-Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, 00189 Roma, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, 00189 Roma, Italy
| | - Vincenzo Marcello Russo
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Damiano Caruso
- Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Michela Polici
- Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Chiara Lauri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
- Correspondence:
| | - Angelina Filice
- Nucler Medicine Unit, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Andrea Laghi
- Radiology Unit, Department of Medical Surgical Sciences and Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
| | - Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, 00189 Roma, Italy
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Fine GC, Covington MF, Koppula BR, Salem AE, Wiggins RH, Hoffman JM, Morton KA. PET-CT in Clinical Adult Oncology-VI. Primary Cutaneous Cancer, Sarcomas and Neuroendocrine Tumors. Cancers (Basel) 2022; 14:2835. [PMID: 35740501 PMCID: PMC9221374 DOI: 10.3390/cancers14122835] [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: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 11/16/2022] Open
Abstract
PET-CT is an advanced imaging modality with many oncologic applications, including staging, therapeutic assessment, restaging and surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, the potential pitfalls and nuances that characterize these applications, and guidelines for image interpretation. Tumor-specific clinical information and representative PET-CT images are provided. The current, sixth article in this series addresses PET-CT in an evaluation of aggressive cutaneous malignancies, sarcomas and neuroendocrine tumors. A discussion of the role of FDG PET for all types of tumors in these categories is beyond the scope of this review. Rather, this article focuses on the most common malignancies in adult patients encountered in clinical practice. It also focuses on Food and Drug Agency (FDA)-approved and clinically available radiopharmaceuticals rather than research tracers or those requiring a local cyclotron. This information will serve as a guide to primary providers for the appropriate role of PET-CT in managing patients with cutaneous malignancies, sarcomas and neuroendocrine tumors. The nuances of PET-CT interpretation as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees, are also addressed.
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Affiliation(s)
- Gabriel C. Fine
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
| | - Matthew F. Covington
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
| | - Bhasker R. Koppula
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
| | - Ahmed Ebada Salem
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
- Faculty of Medicine, Department of Radiodiagnosis and Intervention, Alexandria University, Alexandria 21526, Egypt
| | - Richard H. Wiggins
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
| | - John M. Hoffman
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
| | - Kathryn A. Morton
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (G.C.F.); (M.F.C.); (B.R.K.); (A.E.S.); (R.H.W.); (J.M.H.)
- Intermountain Healthcare Hospitals, Summit Physician Specialists, Murray, UT 84123, USA
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Kaewput C, Vinjamuri S. Role of Combined 68Ga DOTA-Peptides and 18F FDG PET/CT in the Evaluation of Gastroenteropancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2022; 12:diagnostics12020280. [PMID: 35204371 PMCID: PMC8871217 DOI: 10.3390/diagnostics12020280] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 12/12/2022] Open
Abstract
This review article summarizes the role of combined 68Ga DOTA-peptides and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Patients with GEP-NENs can initially present themselves to a gastroenterologist or endocrinologist rather than cancer specialist; hence, it is vital for a wider group of clinicians to be familiar with the range of tests available for the evaluation of these patients. The role of PET scanning by using 68Ga DOTA-peptides has a high sensitivity in the diagnosis of GEP-NENs and to guide patient selection for treatment with somatostatin analogues (SSA) and/or peptide receptor radionuclide therapy (PRRT). The loss of somatostatin receptor (SSTR) expression was found to be associated with an increased glucose metabolism in cells. However, the routine use of SSTR targeted radiotracers in combination with 18F-FDG to evaluate glucose utilization in GEP-NENs is still debatable. In our opinion, in patients with NENs, 18F-FDG PET should be performed in the case of a negative or slightly positive 68Ga DOTA-peptides PET scan for assessing the dedifferentiation status, to guide correct therapeutic strategy and to evaluate the prognosis. The approach of combined receptor and metabolic imaging can improve diagnostic accuracy, especially considering the heterogeneity of these lesions. Therefore, 68Ga DOTA-peptides and 18F-FDG PET should be considered complementary in patients with GEP-NENs.
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Affiliation(s)
- Chalermrat Kaewput
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Correspondence: ; Tel.: +66-2419-6220
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool L7 8XP, UK;
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Majala S, Vesterinen T, Seppänen H, Mustonen H, Sundström J, Schalin-Jäntti C, Gullichsen R, Schildt J, Kemppainen J, Arola J, Kauhanen S. Correlation of Somatostatin Receptor 1-5 Expression, [ 68Ga]Ga-DOTANOC, [ 18F]F-FDG PET/CT and Clinical Outcome in a Prospective Cohort of Pancreatic Neuroendocrine Neoplasms. Cancers (Basel) 2021; 14:cancers14010162. [PMID: 35008325 PMCID: PMC8750461 DOI: 10.3390/cancers14010162] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/23/2021] [Accepted: 12/26/2021] [Indexed: 11/25/2022] Open
Abstract
Simple Summary The need for prognostic and predictive biomarkers in pancreatic neuroendocrine neoplasms (PNENs) is great. Overexpression of somatostatin receptors (SSTRs) provides a molecular basis for imaging these tumors with 68Ga-labeled somatostatin (SST) PET/CT and for treatment with somatostatin analogs. We evaluated all 5 somatostatin receptors (SSTR1-5) with immunohistochemistry and prospectively compared the results with both [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT in a cohort of 21 non-functional (NF) PNENs. SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. High SSTR5 expression correlated with a low Ki-67 proliferation index, suggesting a better prognosis for these patients. Thus, our results confirm that SSTR2 has the highest impact on SSTR PET signaling of PNENs. Abstract Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
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Affiliation(s)
- Susanna Majala
- Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland; (R.G.); (S.K.)
- Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland;
- Correspondence:
| | - Tiina Vesterinen
- HUSLAB, HUS Diagnostic Center, Department of Pathology, Helsinki University Hospital, University of Helsinki, P.O. Box 400, FIN-00029 Helsinki, Finland; (T.V.); (J.A.)
- Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, P.O. Box 20, FIN-00014 Helsinki, Finland
| | - Hanna Seppänen
- Translational Cancer Medicine Research Program, Department of Surgery, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland; (H.S.); (H.M.)
| | - Harri Mustonen
- Translational Cancer Medicine Research Program, Department of Surgery, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland; (H.S.); (H.M.)
| | - Jari Sundström
- Department of Pathology, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland;
| | - Camilla Schalin-Jäntti
- Abdominal Center, Division of Endocrinology, Helsinki University Hospital, University of Helsinki, P.O. Box 340, FIN-00029 Helsinki, Finland;
| | - Risto Gullichsen
- Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland; (R.G.); (S.K.)
| | - Jukka Schildt
- Department of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital, Haartmaninkatu 4, P.O. Box 340, FIN-00029 Helsinki, Finland;
| | - Jukka Kemppainen
- Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland;
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland
| | - Johanna Arola
- HUSLAB, HUS Diagnostic Center, Department of Pathology, Helsinki University Hospital, University of Helsinki, P.O. Box 400, FIN-00029 Helsinki, Finland; (T.V.); (J.A.)
| | - Saila Kauhanen
- Department of Surgery, Division of Digestive Surgery and Urology, Turku University Hospital, University of Turku, P.O. Box 52, FIN-20521 Turku, Finland; (R.G.); (S.K.)
- Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521 Turku, Finland;
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Segaran N, Devine C, Wang M, Ganeshan D. Current update on imaging for pancreatic neuroendocrine neoplasms. World J Clin Oncol 2021; 12:897-911. [PMID: 34733612 PMCID: PMC8546658 DOI: 10.5306/wjco.v12.i10.897] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/21/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
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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Affiliation(s)
- Nicole Segaran
- Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ 85259, United States
| | - Catherine Devine
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mindy Wang
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Dhakshinamoorthy Ganeshan
- Department of Diagnostic Radiology, Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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8
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Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Eur J Radiol 2021; 143:109932. [PMID: 34482177 DOI: 10.1016/j.ejrad.2021.109932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 08/17/2021] [Accepted: 08/21/2021] [Indexed: 12/23/2022]
Abstract
Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) represent a heterogeneous group of rare neoplasms with increasing incidence over the last decades. Localization of GEP-NETs and their metastases is a vital component for the implementation of accurate and patient-tailored treatment strategies. Addressing this challenge requires the employment of multidisciplinary imaging approaches, with hybrid positron emission tomography/computed tomography (PET/CT) imaging techniques standing at the forefront of this effort. GEP-NETs exhibit several pathophysiologic characteristics, which can serve as highly specific molecular targets that can be effectively visualized and quantified by means of PET-radiopharmaceuticals, facilitating diagnosis, accurate staging and efficient monitoring of treatment response. Furthermore, the capability for whole-body, in-vivo, non-invasive characterization of the molecular heterogeneity of the disease, provides strong prognostic information, while enabling the selection of patients suitable for precision-based theranostic approaches. The dual tracer (18F-FDG & 68Ga-DOTA-peptides) PET/CT imaging approach is the current optimal diagnostic imaging strategy, since it enables tumor localization, accurate staging, non-invasive whole-body total tumor burden characterization of disease heterogeneity, while providing strong prognostic information and guidance towards treatment strategy. Moreover, 64Cu-DOTATATE has been recently approved by FDA for SSTRs positive NETs, promising substantial diagnostic and logistical benefits. Furthermore, 18F-DOPA offers diagnostic capabilities for serotonin-secreting GEP-NETs which are not characterized by cell-surface over-expression of somatostatin receptors (SSTRs) and cannot be seen on morphological imaging. In addition, PET/CT with agents targeting the expression of glucagon-like peptide-1 receptor (GLP-R1) should be considered in cases of clinical suspicion for insulinomas that cannot be detected by morphological imaging or STTRs PET/CT imaging.
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Pirasteh A, Lovrec P, Bodei L. Imaging of neuroendocrine tumors: A pictorial review of the clinical value of different imaging modalities. Rev Endocr Metab Disord 2021; 22:539-552. [PMID: 33783695 DOI: 10.1007/s11154-021-09631-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/25/2021] [Indexed: 02/07/2023]
Abstract
Neuroendocrine tumors (NETs) are multifaceted tumors occurring in a variety of organs and often present as metastatic at the time of diagnosis. Accurate staging is the most significant factor in therapy planning, but it remains a challenge. Imaging is established as the cornerstone for disease detection/diagnosis, staging, and follow up. To accurately assess and monitor tumor burden in patients with NETs, various imaging techniques have been developed and optimized. Current recommendations for the imaging of patients with NETs include a combination of both morphologic (or anatomic) and molecular imaging, but a final choice can be puzzling for clinicians. Recognizing that there is no uniform sequence consensus on the "best" imaging test, and the heterogeneity of technologic availability at different centers, we hope to provide a pictorial review of the different imaging techniques and their role and utility in management of patients with NETs, aimed to provide a practical guide for all clinicians.
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Affiliation(s)
- Ali Pirasteh
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, United States.
| | - Petra Lovrec
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, United States
| | - Lisa Bodei
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
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10
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Zhou J, Xie J, Pan Y, Zhang Y. Detection of Adult Pancreatoblastoma by 18F-FDG and 68Ga-DOTATATE PET/MR. Clin Nucl Med 2021; 46:671-674. [PMID: 33661203 DOI: 10.1097/rlu.0000000000003568] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT A 36-year-old asymptomatic woman was incidentally found to have a huge mass in the pancreas by ultrasound during routine health screening. The mass was suspected of neuroendocrine tumor or solid pseudopapillary tumor by subsequent abdominal CT. 18F-FDG and 68Ga-DOTATATE PET/MR were acquired for presurgical assessment of the tumor invasion and malignant potential, which revealed intense FDG uptake and mild DOTATATE uptake. The tumor was completely resected, and postsurgical pathology demonstrated pancreatoblastoma with neuroendocrine manifestations. This case showed the metabolic and biological features of pancreatoblastoma on the 18F-FDG and 68Ga-DOTATATE PET/MR.
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Affiliation(s)
| | - Jing Xie
- Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Yu Pan
- From the Departments of Nuclear Medicine
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Effraimidis G, Knigge U, Rossing M, Oturai P, Rasmussen ÅK, Feldt-Rasmussen U. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin Cancer Biol 2021; 79:141-162. [PMID: 33905872 DOI: 10.1016/j.semcancer.2021.04.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/03/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022]
Abstract
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.
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Affiliation(s)
- Grigoris Effraimidis
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Maria Rossing
- Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Åse Krogh Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulla Feldt-Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Denmark.
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Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13081813. [PMID: 33920195 PMCID: PMC8069875 DOI: 10.3390/cancers13081813] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/05/2021] [Accepted: 04/08/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Functional imaging with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has evolved into a major clinical tool in cancer diagnosis and management for many malignancies in diverse clinical settings, providing valuable information on tumor behavior and aggressiveness. In the field of neuroendocrine tumors (NETs), recent advances in molecular imaging and targeted treatments with novel theranostic agents favor a more patient-tailored approach. Although peptide receptor radionuclide therapy (PRRT) has recently become an established therapy for progressive NETs, the role of 18F-FDG PET prior to PRRT in patients with NETs of different origins and grades remains to be determined. Herein, we provide a comprehensive summary of available evidence in contemporary literature by means of a systematic review and meta-analysis, demonstrating that dual-functional imaging with 68Ga-DOTA-peptides and 18F-FDG prior to PRRT appears to be a useful tool in NET management by delineating tumor somatostatin receptor expression and glycolytic metabolic activity, and predicting tumor response and survival outcomes. Abstract The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27–10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48–4.04 and HR:2.25; 95% CIs:1.55–3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.
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Yadav D, Kumar R. Critical Role of 2-[18F]-fluoro-2-deoxy-glucose in Hormonally Active Malignancies. PET Clin 2021; 16:177-189. [PMID: 33648663 DOI: 10.1016/j.cpet.2020.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
2-[18F]-fluoro-2-deoxyglucose (FDG) is the most commonly used radiotracer and provides valuable information about glucose metabolism. With the advent of newer receptor-based tracers in the management of hormonally active malignancies, the focus has been shifted from FDG. These tracers might be more specific than FDG because they target specific hormone receptors. But because FDG is widely available, this review discusses what information still can be harnessed from this workhorse of molecular imaging. The personalized implementation of FDG imaging in undifferentiated malignancies will help in characterization of tumor and may aid in patient management.
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Affiliation(s)
- Divya Yadav
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, AIIMS, Ansari nagar, New Delhi 110029, India.
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Tanaka M, Heckler M, Mihaljevic AL, Probst P, Klaiber U, Heger U, Schimmack S, Büchler MW, Hackert T. Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2021; 28:1614-1624. [PMID: 32720049 DOI: 10.1245/s10434-020-08850-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 06/27/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND The optimal surgical strategy for pancreatic neuroendocrine tumors (PNETs) is unknown. However, current guidelines recommend a watch-and-wait strategy for small nonfunctional PNETs (NF-PNETs). The aim of this study is to investigate the risk stratification and prognostic significance of lymph node metastasis (LNM) of PNETs to guide decision-making for lymphadenectomy. PATIENTS AND METHODS The MEDLINE and Web of Science databases were systematically searched for studies reporting either risk factors of LNM in resected PNETs or survival of patients with LNM. The weighted average incidence of LNM was calculated according to tumor characteristics. Random-effects metaanalyses were performed, and pooled hazard ratios (HR) and their 95% confidence intervals (CI) were calculated to determine the impact of LNM on overall survival (OS). In subgroup analyses, NF-PNETs were assessed. RESULTS From a total of 5883 articles, 98 retrospective studies with 13,374 patients undergoing resection for PNET were included. In all PNETs, the weighted median rates of LNM were 11.5% for small (≤ 2 cm) PNETs and 15.8% for G1 PNETs. In NF-PNETs, the rates were 11.2% for small PNETs and 10.3% for G1 PNETs. LNM of all PNETs (HR 3.87, 95% CI 3.00-4.99, P < 0.001) and NF-PNETs (HR 4.98, 95% CI 2.81-8.83, P < 0.001) was associated with worse OS. CONCLUSIONS LNM is potentially prevalent even in small and well-differentiated PNETs and is associated with worse prognosis. A watch-and-wait strategy for small NF-PNETs should be reappraised, and oncologic resection with lymphadenectomy can be considered. Prospective and controlled studies are needed in the future.
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Affiliation(s)
- Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of Surgery, Keio University, School of Medicine, Tokyo, Japan
| | - Max Heckler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - André L Mihaljevic
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ulrike Heger
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Simon Schimmack
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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Paiella S, Landoni L, Tebaldi S, Zuffante M, Salgarello M, Cingarlini S, D'Onofrio M, Parisi A, Deiro G, Manfrin E, Bianchi B, Montagnini G, Crinò SF, Bassi C, Salvia R. Dual-Tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT Scan and G1-G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Evaluation of 124 Nonmetastatic Resected Cases. Neuroendocrinology 2021; 112:143-152. [PMID: 33508821 DOI: 10.1159/000514809] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/28/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.
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Affiliation(s)
- Salvatore Paiella
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Luca Landoni
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Sarah Tebaldi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Michele Zuffante
- Nuclear Medicine Unit, Integrated University Hospital of Verona, Verona, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy
| | - Sara Cingarlini
- Pancreas Institute, Oncology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Mirko D'Onofrio
- Pancreas Institute, Radiology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Alice Parisi
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Giacomo Deiro
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Erminia Manfrin
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Beatrice Bianchi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Greta Montagnini
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Francesco Crinò
- Pancreas Institute, Gastroenterology and Digestive Endoscopy Unit, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
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Dual Tracer 68Ga-DOTATOC and 18F-FDG PET Improve Preoperative Evaluation of Aggressiveness in Resectable Pancreatic Neuroendocrine Neoplasms. Diagnostics (Basel) 2021; 11:diagnostics11020192. [PMID: 33525712 PMCID: PMC7912034 DOI: 10.3390/diagnostics11020192] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 01/18/2021] [Accepted: 01/23/2021] [Indexed: 01/06/2023] Open
Abstract
PURPOSE To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. PATIENTS AND METHODS Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52-66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. RESULTS Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1-8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). CONCLUSION Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.
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Calabrò D, Argalia G, Ambrosini V. Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors. Diagnostics (Basel) 2020; 10:E1059. [PMID: 33297381 PMCID: PMC7762240 DOI: 10.3390/diagnostics10121059] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/02/2020] [Accepted: 12/04/2020] [Indexed: 12/12/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emission tomography/computed tomography (PET/CT) has become indispensable for the management of panNENs. Several PET radiopharmaceuticals can be used to characterize either panNEN receptor expression or metabolism. The aim of this review is to offer an overview of all the currently used radiopharmaceuticals and of the new upcoming tracers for pancreatic neuroendocrine tumors (panNETs), and their clinical impact on therapy management. [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) has high sensitivity, specificity, and accuracy and is recommended for the staging and restaging of any non-insulinoma well-differentiated panNEN cases to carry out detection of unknown primary tumor sites or early relapse and for evaluation of in vivo somatostatin receptors expression (SRE) to select patient candidates for peptide receptor radiometabolic treatment (PRRT) with 90Y or 177Lu and/or cold analogs. SSA-PET/CT also has a strong impact on clinical management, leading to a change in treatment in approximately a third of the cases. Its role for treatment response assessment is still under debate due to the lack of standardized criteria, even though some semiquantitative parameters seem to be able to predict response. [18F]FDG PET/CT generally shows low sensitivity in small growing and well-differentiated neuroendocrine tumors (NET; G1 and G2), while it is of utmost importance in the evaluation and management of high-grade NENs and also provides important prognostic information. When positive, [18F]FDG PET/CT impacts therapeutical management, indicating the need for a more aggressive treatment regime. Although FDG positivity does not exclude the patient from PRRT, several studies have demonstrated that it is certainly useful to predict response, even in this setting. The role of [18F]FDOPA for the study of panNET is limited by physiological uptake in the pancreas and is therefore not recommended. Moreover, it provides no information on SRE that has crucial clinical management relevance. Early acquisition of the abdomen and premedication with carbidopa may be useful to increase the accuracy, but further studies are needed to clarify its utility. GLP-1R agonists, such as exendin-4, are particularly useful for benign insulinoma detection, but their accuracy decreases in the case of malignant insulinomas. Being a whole-body imaging technique, exendin-PET/CT gives important preoperative information on tumor size and localization, which is fundamental for surgical planning as resection (enucleation of the lesion or partial pancreatic resection) is the only curative treatment. New upcoming tracers are under study, such as promising SSTR antagonists, which show a favorable biodistribution and higher tumor-to-background ratio that increases tumor detection, especially in the liver. [68Ga]pentixafor, an in vivo marker of CXCR4 expression associated with the behavior of more aggressive tumors, seems to only play a limited role in detecting well-differentiated NET since there is an inverse expression of SSTR2 and CXCR4 in G1 to G3 NETs with an elevation in CXCR4 and a decrease in SSTR2 expression with increasing grade. Other tracers, such as [68Ga]Ga-PSMA, [68Ga]Ga-DATA-TOC, [18F]SiTATE, and [18F]AlF-OC, are also under investigation.
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Affiliation(s)
- Diletta Calabrò
- Department of Nuclear Medicine, IRCCS Azienda Ospedaliera-Universitaria di Bologna, 40138 Bologna, Italy; (G.A.); (V.A.)
- Department of Nuclear Medicine, DIMES University of Bologna, 40138 Bologna, Italy
| | - Giulia Argalia
- Department of Nuclear Medicine, IRCCS Azienda Ospedaliera-Universitaria di Bologna, 40138 Bologna, Italy; (G.A.); (V.A.)
- Department of Nuclear Medicine, DIMES University of Bologna, 40138 Bologna, Italy
| | - Valentina Ambrosini
- Department of Nuclear Medicine, IRCCS Azienda Ospedaliera-Universitaria di Bologna, 40138 Bologna, Italy; (G.A.); (V.A.)
- Department of Nuclear Medicine, DIMES University of Bologna, 40138 Bologna, Italy
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Que R, Chen Y, Tao Z, Ge B, Li M, Fu Z, Li Y. Diffusion-weighted MRI versus FDG-PET/CT for diagnosing pancreatic cancer: an indirect comparison meta-analysis. Acta Radiol 2020; 61:1473-1483. [PMID: 32148066 DOI: 10.1177/0284185120907246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DWI or DW-MRI) are tools for the diagnosis of pancreatic cancer. However, comparison of their diagnostic performance remains unknown. PURPOSE To indirectly compare the diagnostic value of DWI and FDG-PET/CT in the detection of pancreatic cancer. MATERIAL AND METHODS A literature search of PubMed, Embase, and Cochrane Library electronic databases for articles published through May 2018 yielded 875 articles. For the meta-analysis, we included 26 studies evaluating the efficacy of DWI and FDG-PET/CT for determining pancreatic cancer with a total of 1377 patients. QUADAS (Quality Assessment of Diagnostic Accuracy Studies) was used to assess the study quality. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) with their 95% confidence intervals were calculated for each individual study. RESULTS There were no significant differences between DWI and FDG-PET/CT for sensitivity, specificity, PLR, NLR, or DOR, while DWI AUC was higher than that of FDG-PET/CT for the detection of pancreatic cancer. CONCLUSION The diagnostic value of both DWI and FDG-PET/CT were comparable and, hence, both techniques seem to be equally useful tools for the diagnosis of pancreatic cancer.
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Affiliation(s)
- Renye Que
- Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
- Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Yirong Chen
- Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Zhihui Tao
- Department of Oncology, Jiading Hospital of Traditional Chinese Medicine, Shanghai, PR China
| | - Bingjing Ge
- Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Miaohua Li
- Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Zhiquan Fu
- Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Yong Li
- Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
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Combined 68Ga-DOTATOC and 18F-FDG PET Predicts a Double Component With Different Grade of a Pancreatic Neuroendocrine Tumor in a Patient With Multiple Endocrine Neoplasia Type 1. Clin Nucl Med 2020; 45:e281-e282. [PMID: 32349092 DOI: 10.1097/rlu.0000000000003020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Managing decisions of pancreatic neuroendocrine tumors (pNETs) can be challenging because of different clinical presentations and prognosis. A 31-year-old woman with multiple endocrine neoplasia type 1, including a suspicious pNET, was assessed with Ga-DOTATOC and F-FDG PET. A high Ga-DOTATOC uptake was visualized in the entire pNET, whereas a high F-FDG PET uptake was present only in the upper part of the tumor. After surgery, pathology confirmed the pNET with a double component: an upper grade 2 with a Ki67 of 11% with the high F-FDG PET uptake, and a lower grade 1 with a Ki67 of 2%. Combined Ga-DOTATOC/F-FDG PET predicts the grade in heterogeneous pNETs.
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20
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Bauckneht M, Albano D, Annunziata S, Santo G, Guglielmo P, Frantellizzi V, Branca A, Ferrari C, Vento A, Mirabile A, Nappi AG, Evangelista L, Alongi P, Laudicella R. Somatostatin Receptor PET/CT Imaging for the Detection and Staging of Pancreatic NET: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2020; 10:598. [PMID: 32824388 PMCID: PMC7459584 DOI: 10.3390/diagnostics10080598] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 08/13/2020] [Indexed: 12/15/2022] Open
Abstract
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71-87%) and 95% (95%CI: 75-100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65-90%) and 92% (95%CI: 80-97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs.
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Affiliation(s)
- Matteo Bauckneht
- Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy;
| | - Domenico Albano
- Department of Nuclear Medicine, University of Brescia and Spedali Civili Brescia, 25123 Brescia, Italy;
| | - Salvatore Annunziata
- Nuclear Medicine Unit, IRCSS Regina Elena National Cancer Institute, 00168 Rome, Italy;
| | - Giulia Santo
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | | | - Viviana Frantellizzi
- Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Alessia Branca
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Cristina Ferrari
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Antonio Vento
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
| | - Alessia Mirabile
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
| | - Anna Giulia Nappi
- Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70121 Bari, Italy; (G.S.); (A.B.); (C.F.); (A.G.N.)
| | - Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy
| | - Pierpaolo Alongi
- Unit of Nuclear Medicine, Fondazione Istituto G.Giglio, 90015 Cefalù, Italy;
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (A.V.); (A.M.); (R.L.)
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Evangelista L, Ravelli I, Bignotto A, Cecchin D, Zucchetta P. Ga-68 DOTA-peptides and F-18 FDG PET/CT in patients with neuroendocrine tumor: A review. Clin Imaging 2020; 67:113-116. [PMID: 32559681 DOI: 10.1016/j.clinimag.2020.05.035] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 05/18/2020] [Accepted: 05/29/2020] [Indexed: 01/17/2023]
Abstract
OBJECTIVES The aim of the present review was to assess the role of combined 18F-Fluorodeoxyglucose (F-18 FDG) and Ga-68 DOTA-peptides positron emission tomography (PET)-computed tomography (CT) in neuroendocrine tumors (NETs). METHODS We have searched MEDLINE databases, including PubMed and Scopus, for studies about the combined FDG and Ga-68 DOTA-peptides PET-CT or PET/Magnetic Resonance Imaging (MRI) in NETs in the last 15 years (from 2004 to November 2019). No limits were applied to the search strategy. Abstracts, reviews, letters to editors, and editorials were excluded. RESULTS Seven studies met the inclusion criteria. In total 236 patients received both 68Ga-DOTA-peptides and F-18 FDG PET-CT for the characterization of NETs. In particular, 84 patients had a neuroendocrine lung tumor while the others mainly a gastroenteropancreatic NET. The combined use of F-18 FDG and Ga-68 DOTA-peptides (mainly TOC) PET studies provides complementary information regarding different biological characteristics of the lesions, thus enabling a more accurate selection of patients for targeted radionuclide therapy and a better stratification of the prognosis. CONCLUSIONS Ga-68 DOTA-peptides and F-18 FDG PET should be considered complementary in patients with NETs. They should be both performed in the initial staging and during follow-up, with a specific selection of patients and in a multidisciplinary vision.
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Affiliation(s)
- Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy.
| | - Ilaria Ravelli
- Nuclear Medicine Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Antonio Bignotto
- Nuclear Medicine Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Diego Cecchin
- Nuclear Medicine Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy
| | - Pietro Zucchetta
- Nuclear Medicine Unit, Department of Medicine - DIMED, University of Padua, Padua, Italy
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22
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Jin M, Zhou B, Jiang XL, Zhang QY, Zheng X, Jiang YC, Yan S. Flushing as atypical initial presentation of functional gallbladder neuroendocrine carcinoma: A case report. World J Gastroenterol 2020; 26:686-695. [PMID: 32103876 PMCID: PMC7029351 DOI: 10.3748/wjg.v26.i6.686] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 12/31/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder (GB), and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms. CASE SUMMARY We report a case of GB neuroendocrine carcinoma (GB-NEC) in a 65-year-old man, who presented with flushing for 2 mo. Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis. Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space. High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space, but distant metastasis was not seen by positron emission tomography. Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC. Because of the functional characteristics of poorly differentiated NEC, en bloc cholecystectomy, resection of hepatic segments IVb and V, pancreaticoduodenectomy, and regional lymphadenectomy were performed. A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data. Ki-67 index was > 80%. The patient refused adjuvant therapy and passed away in the 7th month. CONCLUSION Distinctive manifestation combined with imaging helps make correct preoperative diagnosis. Radical surgery and adjuvant chemotherapy might improve prognosis.
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Affiliation(s)
- Ming Jin
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Bo Zhou
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Xiong-Ling Jiang
- Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Qi-Yi Zhang
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Xiang Zheng
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Yuan-Cong Jiang
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
| | - Sheng Yan
- Department of General Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
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23
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Majala S, Seppänen H, Kemppainen J, Sundström J, Schalin-Jäntti C, Gullichsen R, Schildt J, Mustonen H, Vesterinen T, Arola J, Kauhanen S. Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT. EJNMMI Res 2019; 9:116. [PMID: 31872324 PMCID: PMC6928175 DOI: 10.1186/s13550-019-0585-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 12/10/2019] [Indexed: 02/06/2023] Open
Abstract
Background Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging 68Ga-DOTANOC and 18F-FDG-PET/CT in patients with NF-PNETs. Methods Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18F-FDG and 68Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or follow-up (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months. Results Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a 68Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18F-FDG-positive tumor. In addition, one 68Ga-DOTANOC-negative patient was 18F-FDG-positive. 18F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. 68Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were 18F-FDG-positive. The 18F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18F-FDG-positive tumors were significantly larger than the 18F-FDG-negative tumors (P = 0.012). 18F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%. Conclusions 18F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18F-FDG-avid NF-PNETs should be referred for surgery. The 68Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade. Trial registration The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.
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Affiliation(s)
- Susanna Majala
- Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.,Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland
| | - Hanna Seppänen
- Department of Abdominal Surgery, Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland
| | - Jukka Kemppainen
- Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.,Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland
| | - Jari Sundström
- Department of Pathology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland
| | - Camilla Schalin-Jäntti
- Department of Endocrinology, Abdominal Center, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland
| | - Risto Gullichsen
- Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland
| | - Jukka Schildt
- Department of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital, Haartmaninkatu 4, FIN-00029, Helsinki, Finland
| | - Harri Mustonen
- Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FIN-00029, Helsinki, Finland
| | - Tiina Vesterinen
- HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 400, FIN-00029, Helsinki, Finland.,Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, P.O. Box 20, FI-00014, Helsinki, Finland
| | - Johanna Arola
- HUSLAB, Department of Pathology, University of Helsinki and Helsinki University Hospital, P.O. Box 400, FIN-00029, Helsinki, Finland
| | - Saila Kauhanen
- Division of Digestive Surgery and Urology, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland. .,Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.
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Xu X, Chen D, Cao L, Feng X, Tong R, Zheng S, Wu J. Spontaneous rupture of solid pseudopapillary tumor of pancreas: A case report and review of literature. Medicine (Baltimore) 2019; 98:e17554. [PMID: 31689759 PMCID: PMC6946308 DOI: 10.1097/md.0000000000017554] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 08/20/2019] [Accepted: 09/19/2019] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Solid pseudopapillary tumors (SPT) account for 1% to 3% of all pancreatic tumors. They have low malignant potential with a favorable prognosis, and predominantly occur in young women. The pathogenesis and clinical behavior of SPT are still uncertain. In addition, most ruptures of SPT were associated with blunt abdominal trauma, while spontaneous ruptures seemed to be quite rare. Up to now, there have been only 3 spontaneous ruptured SPT cases reported worldwide. PATIENT CONCERNS Here, we reported a 22-year-old female patient with left lower abdominal pain. Computed tomography (CT) showed that a hemorrhagic complex solid cystic mass located in the lesser omentum sac. DIAGNOSIS According to pathological findings of tumor specimen, the diagnosis of solid pseudopapillary tumor (SPT) of the pancreas was made. INTERVENTIONS Distal pancreatectomy and splenectomy was carried out. OUTCOMES The patient recovered to normal status within 10 days after surgery. CONCLUSION Besides, we reviewed about 50 cases in literatures to find out the clinical characteristics and differential diagnostic strategies of SPT.
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Affiliation(s)
- Xiaofeng Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
| | - Diyu Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
| | - Linping Cao
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
| | - Xiaode Feng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
| | - Rongliang Tong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University
- Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health
- Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
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25
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Long-acting octreotide treatment has no impact on tumor uptake of 99mTc-HYNIC-TOC in patients with neuroendocrine tumors. Nucl Med Commun 2019; 40:1005-1010. [DOI: 10.1097/mnm.0000000000001075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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26
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Carideo L, Prosperi D, Panzuto F, Magi L, Pratesi MS, Rinzivillo M, Annibale B, Signore A. Role of Combined [ 68Ga]Ga-DOTA-SST Analogues and [ 18F]FDG PET/CT in the Management of GEP-NENs: A Systematic Review. J Clin Med 2019; 8:1032. [PMID: 31337043 PMCID: PMC6678236 DOI: 10.3390/jcm8071032] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 07/04/2019] [Accepted: 07/08/2019] [Indexed: 02/06/2023] Open
Abstract
Gastro-entero-pancreatic neuroendocrine neoplasia (GEP-NENs) are rare tumors, but their frequency is increasing. Neuroendocrine tumors normally express somatostatin (SST) receptors (SSTR) on cell surface, especially G1 and G2 stage tumors, but they can show a dedifferentiation in their clinical history as they become more aggressive. Somatostatin receptor imaging has previously been performed with a gamma camera using [111In]In or [99mTc]Tc-labelled compounds, while [68Ga]Ga-labelled compounds and PET/CT imaging has recently become the gold standard for the diagnosis and management of these tumors. Moreover, in the last few years 18F-fluorodeoxyglucose ([18F]FDG) PET/CT has emerged as an important tool to define tumor aggressiveness and give relevant prognostic information, particularly when coupled with [68Ga]Ga-labelled SST analogues PET/CT. This review focuses on the importance of combined imaging with [68Ga]Ga-labelled SST analogues and [18F]FDG for the management of GEP-NENs.
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Affiliation(s)
- Luciano Carideo
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Daniela Prosperi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy.
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Ludovica Magi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Maria Sole Pratesi
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Alberto Signore
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189 Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
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27
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Muffatti F, Partelli S, Cirocchi R, Andreasi V, Mapelli P, Picchio M, Gianolli L, Falconi M. Combined 68Ga-DOTA-peptides and 18F-FDG PET in the diagnostic work-up of neuroendocrine neoplasms (NEN). Clin Transl Imaging 2019. [DOI: 10.1007/s40336-019-00328-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18:837-860. [PMID: 29973077 PMCID: PMC6283410 DOI: 10.1080/14737140.2018.1496822] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.
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Affiliation(s)
- Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| | - Tetsuhide Ito
- c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
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29
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Rinzivillo M, Partelli S, Prosperi D, Capurso G, Pizzichini P, Iannicelli E, Merola E, Muffatti F, Scopinaro F, Schillaci O, Salgarello M, Falconi M, Delle Fave G, Panzuto F. Clinical Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography in the Diagnostic Algorithm of Advanced Entero-Pancreatic Neuroendocrine Neoplasms. Oncologist 2018; 23:186-192. [DOI: - rinzivillo m, partelli s, prosperi d, capurso g, pizzichini p, iannicelli e, merola e, et al.clinical usefulness of 18f-fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced entero-pancreatic neuroendocrine neoplasms.oncologist.2017 nov 8.pii: theoncologist.2017-0278.doi: 10.1634/theoncologist.2017-0278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
Abstract
Abstract
Background
The role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the diagnostic algorithm of entero-pancreatic neuroendocrine neoplasms (EP NENs) is unclear because most available data derive from heterogeneous populations in terms of tumor biology and disease status at time of examination. The aim of this study was to determine the ability of 18F-FDG PET to identify patients with more aggressive disease among those with advanced EP NENs.
Subjects, Materials, and Methods . Patients with advanced EP NENs and known disease status (progressive disease [PD] or stable disease [SD]) according to imaging procedures, who received 18F-FDG PET and computed tomography scans during a time frame of 1 month, were included.
Results
A total of 93 patients, including 69 patients with pancreatic NENs and 24 patients with small-intestine NENs, were included. At the time of study entry, 64 patients (68.8%) had PD, and the remaining 29 patients (31.2%) had SD. A total of 62 patients (66.7%) had positive 18F-FDG PET, whereas 18F-FDG PET was negative in the remaining 31 patients (33.3%). Overall, 18F-FDG PET sensitivity and specificity to detect PD were 90.6% and 86.2%, respectively, resulting in a diagnostic accuracy of 89.2%. A positive 18F-FDG PET was significantly associated with PD at the time of study entry (p < .0001 at multivariate analysis). Although a higher proportion of 18F-FDG PET-positive examinations were observed in patients with higher tumor grade (p = .01), 53.8% of patients with grade 1 neuroendocrine tumors (NETs) had positive 18F-FDG PET, and 37.5% of patients with grade 2 NETs had negative 18F-FDG PET. Overall survival was significantly shorter in 18F-FDG PET-positive patients (median: 60 months) in comparison with 18F-FDG PET-negative patients (median not reached; p = .008).
Conclusion
18F-FDG PET has a high diagnostic accuracy to identify progression of disease with unfavorable clinical outcome in patients with advanced EP NENs. Knowledge of disease status and G grading are key factors for physicians to better select patients for whom 18F-FDG PET is clinically useful.
Implications for Practice
The findings of the present study may help physicians dealing with advanced neuroendocrine neoplasms to select patients for whom 18F-fluorodeoxyglucose positron emission tomography is useful to predict poor clinical outcome.
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Affiliation(s)
- Maria Rinzivillo
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Daniela Prosperi
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Patrizia Pizzichini
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Elsa Iannicelli
- Department of Radiology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Elettra Merola
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Francesca Muffatti
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Francesco Scopinaro
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Orazio Schillaci
- Department of Nuclear Medicine, University of Tor Vergata, Rome, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Francesco Panzuto
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
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30
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Rinzivillo M, Partelli S, Prosperi D, Capurso G, Pizzichini P, Iannicelli E, Merola E, Muffatti F, Scopinaro F, Schillaci O, Salgarello M, Falconi M, Delle Fave G, Panzuto F. Clinical Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography in the Diagnostic Algorithm of Advanced Entero-Pancreatic Neuroendocrine Neoplasms. Oncologist 2018; 23:186-192. [PMID: 29118267 PMCID: PMC5813750 DOI: 10.1634/theoncologist.2017-0278] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 09/26/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the diagnostic algorithm of entero-pancreatic neuroendocrine neoplasms (EP NENs) is unclear because most available data derive from heterogeneous populations in terms of tumor biology and disease status at time of examination. The aim of this study was to determine the ability of 18F-FDG PET to identify patients with more aggressive disease among those with advanced EP NENs. Subjects, Materials, and Methods . Patients with advanced EP NENs and known disease status (progressive disease [PD] or stable disease [SD]) according to imaging procedures, who received 18F-FDG PET and computed tomography scans during a time frame of 1 month, were included. RESULTS A total of 93 patients, including 69 patients with pancreatic NENs and 24 patients with small-intestine NENs, were included. At the time of study entry, 64 patients (68.8%) had PD, and the remaining 29 patients (31.2%) had SD. A total of 62 patients (66.7%) had positive 18F-FDG PET, whereas 18F-FDG PET was negative in the remaining 31 patients (33.3%). Overall, 18F-FDG PET sensitivity and specificity to detect PD were 90.6% and 86.2%, respectively, resulting in a diagnostic accuracy of 89.2%. A positive 18F-FDG PET was significantly associated with PD at the time of study entry (p < .0001 at multivariate analysis). Although a higher proportion of 18F-FDG PET-positive examinations were observed in patients with higher tumor grade (p = .01), 53.8% of patients with grade 1 neuroendocrine tumors (NETs) had positive 18F-FDG PET, and 37.5% of patients with grade 2 NETs had negative 18F-FDG PET. Overall survival was significantly shorter in 18F-FDG PET-positive patients (median: 60 months) in comparison with 18F-FDG PET-negative patients (median not reached; p = .008). CONCLUSION 18F-FDG PET has a high diagnostic accuracy to identify progression of disease with unfavorable clinical outcome in patients with advanced EP NENs. Knowledge of disease status and G grading are key factors for physicians to better select patients for whom 18F-FDG PET is clinically useful. IMPLICATIONS FOR PRACTICE The findings of the present study may help physicians dealing with advanced neuroendocrine neoplasms to select patients for whom 18F-fluorodeoxyglucose positron emission tomography is useful to predict poor clinical outcome.
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Affiliation(s)
- Maria Rinzivillo
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Stefano Partelli
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Daniela Prosperi
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Patrizia Pizzichini
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Elsa Iannicelli
- Department of Radiology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Elettra Merola
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Francesca Muffatti
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Francesco Scopinaro
- Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Orazio Schillaci
- Department of Nuclear Medicine, University of Tor Vergata, Rome, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy
| | - Gianfranco Delle Fave
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - Francesco Panzuto
- Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
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Management of Pancreatic and Duodenal Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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PET–Computed Tomography and Precision Medicine in Pancreatic Adenocarcinoma and Pancreatic Neuroendocrine Tumors. PET Clin 2017; 12:407-421. [DOI: 10.1016/j.cpet.2017.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Hindié E. The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors. Am J Cancer Res 2017; 7:1159-1163. [PMID: 28435455 PMCID: PMC5399583 DOI: 10.7150/thno.19588] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis. Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors, ranging from indolent to aggressive, even within apparently homogeneous categories. Thus, selecting the optimal treatment strategy is a challenging task. Somatostatin receptor imaging (SRI) is the standard molecular imaging technique for well-differentiated NET. When performed with 68Ga-labeled somatostatin analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is also a prerequisite for using targeted radionuclide therapy (e.g. 177Lu-DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly-differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG imaging has prognostic value in patients with well-differentiated NET: high uptake was associated with an increased risk of early progression while low uptake suggested an indolent tumor. In this issue of the Journal, Chan and colleagues propose a grading system where the results from the combined reading of SRI-PET and FDG-PET are reported as a single parameter, the "NETPET" score. While the scoring system still needs validation, it is clear that time has come to think about FDG and SRI in metastatic NET not as competitors but as complementary imaging modalities. Dual-tracer imaging can be viewed as a way to characterize disease phenotype in the whole-body. Moving from the prognostic value of dual-tracer imaging to a tool that allows for individualized management would require prospective trials. This editorial will argue that dual-tracer FDG-PET and SRI-PET might influence management of patients with well-differentiated metastatic NET and help selecting between different therapy options.
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