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Kong G, Noe G, Chiang C, Herrmann K, Hope TA, Michael M. Assessment of response to PRRT including anatomical and molecular imaging as well as novel biomarkers. J Neuroendocrinol 2025; 37:e13461. [PMID: 39520276 PMCID: PMC11919480 DOI: 10.1111/jne.13461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 09/05/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
Peptide receptor radionuclide therapy (PRRT) is an effective treatment for both oncological and hormone control and is a widely accepted standard of care treatment for patients with neuroendocrine neoplasms (NEN). Its use is anticipated to increase significantly, and this demands accurate tools and paradigms to assess treatment response post PRRT. This article outlines the current role and future developments of anatomical, molecular imaging and biomarkers for response assessment to PRRT, highlighting the challenges and provides perspectives for the need to focus on a multimodality, multidisciplinary and individualised approach for patients with this complex heterogeneous disease.
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Affiliation(s)
- Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear MedicinePeter MacCallum Cancer CentreMelbourneVictoriaAustralia
- Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneVictoriaAustralia
| | - Geertje Noe
- Department of Cancer ImagingPeter MacCallum Cancer CentreMelbourneVictoriaAustralia
| | - Cherie Chiang
- Department of Internal MedicinePeter MacCallum Cancer CentreParkvilleVictoriaAustralia
- Department of Diabetes and Endocrinology, Melbourne HealthUniversity of MelbourneParkvilleVictoriaAustralia
| | - Ken Herrmann
- Department of Nuclear MedicineUniversity of Duisburg‐Essen and German Cancer Consortium (DKTK)‐University Hospital EssenEssenGermany
| | - Thomas A. Hope
- Department of RadiologySan Francisco VA Medical CenterSan FranciscoCaliforniaUSA
- Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Michael Michael
- Sir Peter MacCallum Department of OncologyUniversity of MelbourneMelbourneVictoriaAustralia
- Department of Medical OncologyPeter MacCallum Cancer CentreMelbourneVictoriaAustralia
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Ataya J, Mostafa MO, Alisame K, Souleiman YI. Precise diagnosis and effective management of highly vascular anterior mediastinal paragangliomas: A case report. Int J Surg Case Rep 2025; 127:110828. [PMID: 39778496 PMCID: PMC11760295 DOI: 10.1016/j.ijscr.2025.110828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/25/2024] [Accepted: 01/02/2025] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Mediastinal paragangliomas are rare neoplasms arising from extra-adrenal neural crest cells, presenting as either functional or nonfunctional tumors. Clinical manifestations range from catecholamine-related symptoms to physical compression effects. Accurate recognition of these tumors is crucial for diagnosis and management due to their rarity and association with vital mediastinal structures. PRESENTATION OF CASE We report the case of a 53-year-old Syrian male presenting with progressive dyspnea, fatigue, and weakness. Imaging revealed a highly vascular anterior mediastinal mass compressing the superior vena cava, diagnosed as a nonfunctional paraganglioma. Preoperative evaluations included endocrine consultation and blood transfusion preparations. The tumor was surgically excised via lateral thoracotomy without complications. Postoperative imaging confirmed the absence of residual mass, and two years of regular follow-ups revealed no recurrence or metastasis. DISCUSSION Mediastinal paragangliomas pose diagnostic and management challenges due to their rarity and potential for extensive vascular involvement. Nonfunctional paragangliomas, in particular, may remain asymptomatic until they exert significant mass effects. Surgical resection is the definitive treatment, often requiring a multidisciplinary approach. Tumor size and patient age influence malignancy risk and recurrence, highlighting the need for thorough perioperative planning and long-term follow-up. CONCLUSION This case underscores the importance of precise diagnosis, meticulous perioperative management, and surgical intervention in managing mediastinal paragangliomas. Lifelong monitoring is essential, especially for larger tumors, to ensure early detection of recurrence. Comprehensive understanding and documentation of such cases contribute to improved patient outcomes and enhanced clinical management strategies.
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Affiliation(s)
- Jamal Ataya
- Faculty of Medicine, University of Aleppo, Aleppo, Syria.
| | | | - Komai Alisame
- Department of Thoracic surgery, Damascus University, Damascus, Syria
| | - Younes Ibrahim Souleiman
- Department of Thoracic surgery, National University Hospital, Damascus University, Damascus, Syria
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Asmundo L, Ambrosini V, Mojtahed A, Fanti S, Ferrone C, Hesami M, Sertic M, Najmi Z, Furtado FS, Dhami RS, Anderson MA, Samir A, Sharma A, Campana D, Ursprung S, Nikolau K, Domachevsky L, Blake MA, Norris EC, Clark JW, Catalano OA. Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know. J Comput Assist Tomogr 2024; 48:628-639. [PMID: 38626751 DOI: 10.1097/rct.0000000000001619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.
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Affiliation(s)
| | | | - Amirkasra Mojtahed
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Cristina Ferrone
- Department of Surgery, Cedar-Sinai Health System, Los Angeles, CA
| | - Mina Hesami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Madeleine Sertic
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Zahra Najmi
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Felipe S Furtado
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ranjodh S Dhami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Mark A Anderson
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Anthony Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Amita Sharma
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Davide Campana
- Department of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Konstantin Nikolau
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Liran Domachevsky
- Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Michael A Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Evan C Norris
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jeffrey W Clark
- Department of Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Padmanabhan Nair Sobha R, Jensen CT, Waters R, Calimano-Ramirez LF, Virarkar MK. Appendiceal Neuroendocrine Neoplasms: A Comprehensive Review. J Comput Assist Tomogr 2024; 48:545-562. [PMID: 37574653 DOI: 10.1097/rct.0000000000001528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/15/2023]
Abstract
ABSTRACT Appendiceal neuroendocrine neoplasm (NEN) is the most common adult appendiceal malignant tumor, constituting 16% of gastrointestinal NENs. They are versatile tumors with varying morphology, immunohistochemistry, secretory properties, and cancer genomics. They are slow growing and clinically silent, to begin with, or present with features of nonspecific vague abdominal pain. Most acute presentations are attributed clinically to appendicitis, with most cases detected incidentally on pathology after an appendectomy. Approximately 40% of them present clinically with features of hormonal excess, which is likened to the functional secretory nature of their parent cell of origin. The symptoms of carcinoid syndrome render their presence clinically evident. However, slow growing and symptomatically silent in its initial stages, high-grade neuroendocrine tumors and neuroendocrine carcinomas of the appendix are aggressive and usually have hepatic and lymph node metastasis at presentation. This review article focuses on imaging characteristics, World Health Organization histopathological classification and grading, American Joint Committee on Cancer/Union or International Cancer Control, European Neuroendocrine Tumor Society staging, European Neuroendocrine Tumor Society standardized guidelines for reporting, data interpretation, early-stage management protocols, and advanced-stage appendiceal NENs. Guidelines are also set for the follow-up and reassessment. The role of targeted radiotherapy, chemotherapy, and high-dose somatostatin analogs in treating advanced disease are discussed, along with types of ablative therapies and liver transplantation for tumor recurrence. The search for newer location-specific biomarkers in NEN is also summarized. Regarding the varying aggressiveness of the tumor, there is a scope for research in the field, with plenty of data yet to be discovered.
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Affiliation(s)
| | - Corey T Jensen
- From the Department of Radiology, University of Texas MD Anderson Cancer Center
| | - Rebecca Waters
- Department of Pathology and Lab Medicine MD Anderson Cancer Center, Houston, TX
| | | | - Mayur K Virarkar
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL
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Ambrosini V, Fortunati E, Fanti S, Ursprung S, Asmundo L, O'Shea A, Kako B, Lee S, Furtado FS, Blake M, Goiffon RJ, Najmi Z, Hesami M, Murakami T, Domachevsky L, Catalano OA. State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms. J Comput Assist Tomogr 2024; 48:510-520. [PMID: 38518197 DOI: 10.1097/rct.0000000000001594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/24/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.
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Affiliation(s)
| | - Emilia Fortunati
- From the Nuclear Medicine, Alma Mater Studiorum, University of Bologna
| | | | | | | | - Aileen O'Shea
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Bashar Kako
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Susanna Lee
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Felipe S Furtado
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Michael Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Reece J Goiffon
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Zahra Najmi
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Mina Hesami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Takaaki Murakami
- Department of Diabetes, Endocrinology and Nutrition, Kyoto University Hospital, Kyoto, Japan
| | - Liran Domachevsky
- Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Liu M, Cheng Y, Bai C, Zhao H, Jia R, Chen J, Zhu W, Huo L. Gallium-68 labeled somatostatin receptor antagonist PET/CT in over 500 patients with neuroendocrine neoplasms: experience from a single center in China. Eur J Nucl Med Mol Imaging 2024; 51:2002-2011. [PMID: 38337073 DOI: 10.1007/s00259-024-06639-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 02/04/2024] [Indexed: 02/12/2024]
Abstract
PURPOSE Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. METHODS Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. RESULTS A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). CONCLUSION Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile.
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Affiliation(s)
- Meixi Liu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yuejuan Cheng
- Department of Oncology, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing, 100730, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ru Jia
- Department of Gastrointestinal Oncology, the fifth Medical Center, General Hospital of PLA, Beijing, China
| | - Jingci Chen
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Wenjia Zhu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Li Huo
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Lamberti G, Panzuto F, Pavel M, O'Toole D, Ambrosini V, Falconi M, Garcia-Carbonero R, Riechelmann RP, Rindi G, Campana D. Gastric neuroendocrine neoplasms. Nat Rev Dis Primers 2024; 10:25. [PMID: 38605021 DOI: 10.1038/s41572-024-00508-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 04/13/2024]
Abstract
Gastric neuroendocrine neoplasms (gNENs) display peculiar site-specific features among all NENs. Their incidence and prevalence have been rising in the past few decades. gNENs comprise gastric neuroendocrine carcinomas (gNECs) and gastric neuroendocrine tumours (gNETs), the latter further classified into three types. Type I anatype II gNETs are gastrin-dependent and develop in chronic atrophic gastritis and as part of Zollinger-Ellison syndrome within a multiple endocrine neoplasia type 1 syndrome (MEN1), respectively. Type III or sporadic gNETs develop in the absence of hypergastrinaemia and in the context of a near-normal or inflamed gastric mucosa. gNECs can also develop in the context of variable atrophic, relatively normal or inflamed gastric mucosa. Each gNEN type has different clinical characteristics and requires a different multidisciplinary approach in expert dedicated centres. Type I gNETs are managed mainly by endoscopy or surgery, whereas the treatment of type II gNETs largely depends on the management of the concomitant MEN1. Type III gNETs may require both locoregional approaches and systemic treatments; NECs are often metastatic and therefore require systemic treatment. Specific data regarding the systemic treatment of gNENs are lacking and are derived from the treatment of intestinal NETs and NECs. An enhanced understanding of molecular and clinical pathophysiology is needed to improve the management and outcomes of patients' gNETs.
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Affiliation(s)
- Giuseppe Lamberti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany
| | - Dermot O'Toole
- National Centre for Neuroendocrine Tumours, ENETS Centre of Excellence, St. Vincent's University Hospital, Dublin, Ireland
- Trinity College Dublin, St. James Hospital, Dublin, Ireland
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Rocio Garcia-Carbonero
- Medicine Department, Universidad Complutense de Madrid, Madrid, Spain
- Oncology Department, Hospital Universitario 12 de Octubre, Imas12, Madrid, Spain
| | | | - Guido Rindi
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli - IRCCS, ENETS Center of Excellence, Rome, Italy
| | - Davide Campana
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
- Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
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Liu Y, Cui R, Wang Z, Lin Q, Tang W, Zhang B, Li G, Wang Z. Evaluating Prognosis of Gastrointestinal Metastatic Neuroendocrine Tumors: Constructing a Novel Prognostic Nomogram Based on NETPET Score and Metabolic Parameters from PET/CT Imaging. Pharmaceuticals (Basel) 2024; 17:373. [PMID: 38543159 PMCID: PMC10975134 DOI: 10.3390/ph17030373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/27/2024] [Accepted: 03/07/2024] [Indexed: 01/06/2025] Open
Abstract
INTRODUCTION The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. METHODS In this retrospective study, G1-G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. RESULTS In this study, 223 patients (130 males; mean age ± SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1-D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). CONCLUSIONS New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts.
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Affiliation(s)
- Yifan Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Ruizhe Cui
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Zhixiong Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Qi Lin
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Wei Tang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Bing Zhang
- Department of Nuclear Medicine, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China;
| | - Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, Zhongshan 2nd Street, No. 58, Guangzhou 510080, China; (Y.L.); (R.C.); (Z.W.); (Q.L.); (W.T.)
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Harini K, Jayanthi MR, Hari KSV, Batchu S. A Rare Presentation of Extrahepatic Biliary Neuroendocrine Tumor Diagnosed using 68Ga-DOTA-TOC Imaging, But Undetectable on 68Ga-FAPI Imaging. Indian J Nucl Med 2024; 39:155-157. [PMID: 38989315 PMCID: PMC11232718 DOI: 10.4103/ijnm.ijnm_149_23] [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: 12/25/2023] [Revised: 02/22/2024] [Accepted: 02/27/2024] [Indexed: 07/12/2024] Open
Abstract
Neuroendocrine tumors (NETs) are commonly seen in the small intestine and rarely found within the bile ducts. This low incidence is due to a smaller number of Kulchitsky cells in the extrahepatic biliary tree, which predisposes to the disease. The diagnosis of biliary tree carcinoid preoperatively is very rare, with most cases in the literature being incidentally diagnosed during surgery or being identified on the histopathology report postoperatively. Here, we present an interesting case of an extrahepatic biliary NET which was diagnosed preoperatively.
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Affiliation(s)
- Koorma Harini
- Department of Nuclear Medicine and PET-CT, AIG Hospitals, Hyderabad, Telangana, India
| | - Mohan Roop Jayanthi
- Department of Nuclear Medicine and PET-CT, AIG Hospitals, Hyderabad, Telangana, India
| | - K S Vishnu Hari
- Department of Nuclear Medicine and PET-CT, AIG Hospitals, Hyderabad, Telangana, India
| | - Suneetha Batchu
- Department of Nuclear Medicine and PET-CT, AIG Hospitals, Hyderabad, Telangana, India
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10
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Ouvrard E, Kaseb A, Poterszman N, Porot C, Somme F, Imperiale A. Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine? Front Med (Lausanne) 2024; 10:1320574. [PMID: 38288299 PMCID: PMC10823373 DOI: 10.3389/fmed.2023.1320574] [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: 10/12/2023] [Accepted: 12/28/2023] [Indexed: 01/31/2024] Open
Abstract
Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.
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Affiliation(s)
- Eric Ouvrard
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Ashjan Kaseb
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
- Radiology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia
| | - Nathan Poterszman
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Clémence Porot
- Radiopharmacy, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg, France
| | - Francois Somme
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
| | - Alessio Imperiale
- Nuclear Medicine and Molecular Imaging, Institut de Cancérologie Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France
- IPHC, UMR 7178, CNRS/Unistra, Strasbourg, France
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11
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Chalikandy A, Basu S. Middle Ear Cavity and Mastoid Neuroendocrine Tumor Presenting as Otomastoiditis with Cholesteatoma: A Clinicoradiological and Histopathological Correlation. World J Nucl Med 2023; 22:310-315. [PMID: 38152101 PMCID: PMC10751138 DOI: 10.1055/s-0043-1777695] [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] [Indexed: 12/29/2023] Open
Abstract
Neuroendocrine tumors of the middle ear are rare, comprising of less than 2% of primary tumors of the ear. The clinical and imaging findings of these tumors are nonspecific, and histological and immunohistochemical findings are confirmatory. Herein, we present a case of 48-year-old male, presenting with chief complaints of hearing loss of left ear with foul smelling discharge, with the initial clinical impression of otomastoiditis of the middle ear with cholesteatoma and being operated for the same, the final histopathology report inferred it as well-differentiated neuroendocrine tumor grade 1 with Ki-67 index less than 2%. Immunohistochemical examinations demonstrated positive staining of the tumor cells for cytokeratin, synaptophysin and chromogranin A, and negative for smooth muscle actin, desmin, S-100. The biochemical investigations showed raised serum chromogranin A levels. Based upon the findings on anatomical imaging modalities including high-resolution computed tomography temporal bone and magnetic resonance imaging paranasal sinuses (MRI PNS), the lesion was inferred inoperable due to involvement of dura of petrous apex, and therefore he was referred for consideration of peptide receptor radionuclide therapy (PRRT). MRI PNS also showed involvement of the horizontal part of facial nerve, indicating local aggressiveness of the tumor. 68 Ga-DOTATATE-PET/CT showed high-grade somatostatin receptor expressing soft tissue lesion involving middle ear and external auditory canal (Krenning's score 4), with low-grade metabolic activity on 18 F-FDG-PET/CT. The post-therapy scan following 177 Lu-DOTATATE PRRT, showed abnormal tracer concentration at the described site. Due to extreme rarity of this disease entity, it is important to accrue data for accurate diagnosis, proper management, and follow-up.
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Affiliation(s)
- Ashwini Chalikandy
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai, Maharashtra, India
- Homi Bhabha National Institute, Mumbai, Maharashtra, India
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12
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Hindré R, Poté N, Mordant P, Le Guen P. [Infectious pneumonia favored by paraneoplastic Cushing syndrome in a pulmonary carcinoid tumor]. Rev Mal Respir 2023; 40:716-722. [PMID: 37633811 DOI: 10.1016/j.rmr.2023.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 06/29/2023] [Indexed: 08/28/2023]
Abstract
INTRODUCTION Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections. CASE REPORT We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC. Further investigations confirmed ectopic ACTH secretion and revealed a right upper lobe pulmonary nodule. After appropriate antibiotic therapy, the patient received preoperative adrenolytic treatment. Management by right upper lobectomy resulted in the extraction of a 12mm tumor. Pathological analysis was consistent with the diagnosis of a typical carcinoid tumor. Immunohistochemistry confirmed ACTH secretion by the tumor. Even though the postoperative course showed CS regression, the patient developed adrenal insufficiency. CONCLUSION Ectopic CS induces immunosuppression, which aggravates lower respiratory tract infections. Search for a pulmonary neuroendocrine tumor should be systematic. Following control of the secretory syndrome by adrenolytic treatment, and if the diagnosis of carcinoid tumor is confirmed, surgical treatment is the preferred option.
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Affiliation(s)
- R Hindré
- Service de pneumologie, centre de référence des maladies pulmonaires rares, FHU APOLLO, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France
| | - N Poté
- Département d'anatomo-pathologie, hôpital Bichat, AP-HP, 75018 Paris, France
| | - P Mordant
- Service de chirurgie vasculaire, thoracique, et transplantation pulmonaire, hôpital Bichat, AP-HP, 75018 Paris, France
| | - P Le Guen
- Service de pneumologie, centre de référence des maladies pulmonaires rares, FHU APOLLO, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France.
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13
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Fabritius MP, Soltani V, Cyran CC, Ricke J, Bartenstein P, Auernhammer CJ, Spitzweg C, Schnitzer ML, Ebner R, Mansournia S, Hinterberger A, Lohse A, Sheikh GT, Winkelmann M, Knösel T, Ingenerf M, Schmid-Tannwald C, Kunz WG, Rübenthaler J, Grawe F. Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors. Cancer Imaging 2023; 23:92. [PMID: 37770958 PMCID: PMC10537814 DOI: 10.1186/s40644-023-00614-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 09/19/2023] [Indexed: 09/30/2023] Open
Abstract
BACKGROUND Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.
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Affiliation(s)
- M P Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - V Soltani
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - C C Cyran
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - J Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - P Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - C J Auernhammer
- Department of Internal Medicine 4, University Hospital, LMU Munich, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - C Spitzweg
- Department of Internal Medicine 4, University Hospital, LMU Munich, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - M L Schnitzer
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - R Ebner
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - S Mansournia
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - A Hinterberger
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - A Lohse
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - G T Sheikh
- Department of Nuclear Medicine, University Hospital, LMU Munich, 81377, Munich, Germany
| | - M Winkelmann
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - T Knösel
- Department of Pathology, University Hospital, LMU Munich, 81377, Munich, Germany
| | - M Ingenerf
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - C Schmid-Tannwald
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - W G Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - J Rübenthaler
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
- Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM, ENETS certified Center of Excellence), University Hospital, LMU Munich, 81377, Munich, Germany
| | - Freba Grawe
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
- Department of Nuclear Medicine, University Hospital, LMU Munich, 81377, Munich, Germany.
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14
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Zhang JM, Zheng CW, Li XW, Fang ZY, Yu MX, Shen HY, Ji X. Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature. World J Clin Cases 2023; 11:6223-6230. [PMID: 37731553 PMCID: PMC10507545 DOI: 10.12998/wjcc.v11.i26.6223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/25/2023] [Accepted: 08/11/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.
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Affiliation(s)
- Jin-Ming Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Chu-Wei Zheng
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Xiao-Wen Li
- Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Zhi-Yun Fang
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Mu-Xin Yu
- College of Medicine, Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Hai-Yan Shen
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Xia Ji
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
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15
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Lim J, Patel M. Mesenteric Paraganglioma: A Case Report and Literature Review. Cureus 2023; 15:e45685. [PMID: 37868495 PMCID: PMC10590082 DOI: 10.7759/cureus.45685] [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] [Accepted: 09/21/2023] [Indexed: 10/24/2023] Open
Abstract
We report a rare case of a solitary paraganglioma arising from the small bowel mesentery, found in a 70-year-old female who presented with abdominal pain. Paragangliomas are rare neuroendocrine, neural crest-derived tumors, most commonly found in the adrenal medulla. While extra-adrenal paragangliomas arise from diverse locations, mesenteric origins are extremely rare. Our comprehensive review shows 35 previously documented cases and updates the epidemiology, clinical features, and outcomes of mesenteric paragangliomas.
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Affiliation(s)
- Jihoon Lim
- College of Medicine, University of Central Florida College of Medicine, Orlando, USA
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16
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Navin PJ, Ehman EC, Liu JB, Halfdanarson TR, Gupta A, Laghi A, Yoo DC, Carucci LR, Schima W, Sheedy SP. Imaging of Small-Bowel Neuroendocrine Neoplasms: AJR Expert Panel Narrative Review. AJR Am J Roentgenol 2023; 221:289-301. [PMID: 36752369 DOI: 10.2214/ajr.22.28877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
Neuroendocrine neoplasms (NENs) of the small bowel are typically slow-growing lesions that remain asymptomatic until reaching an advanced stage. Imaging modalities for lesion detection, staging, and follow-up in patients with known or suspected NEN include CT enterography, MR enterography, and PET/CT using a somatostatin receptor analog. FDG PET/CT may have a role in the evaluation of poorly differentiated NENs. Liver MRI, ideally with a hepatocyte-specific contrast agent, should be used in the evaluation of hepatic metastases. Imaging informs decisions regarding both surgical approaches and systematic therapy (specifically, peptide receptor radionuclide therapy). This AJR Expert Panel Narrative Review describes the multimodality imaging features of small-bowel NENs; explores the optimal imaging modalities for their diagnosis, staging, and follow-up; and discusses how imaging may be used to guide therapy.
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Affiliation(s)
- Patrick J Navin
- Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905
| | - Eric C Ehman
- Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905
| | - Jason B Liu
- Department of Surgery, Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA
| | | | - Akshya Gupta
- Department of Imaging Sciences, University of Rochester, Rochester, NY
| | - Andrea Laghi
- Department of Medical Surgical Sciences and Translational Medicine, AOU Sant'Andrea, Sapienza University of Rome, Rome, Italy
| | - Don C Yoo
- Department of Diagnostic Imaging, The Warren Alpert Medical School of Brown University, Providence, RI
| | - Laura R Carucci
- Department of Radiology, Virginia Commonwealth University Medical Center, Richmond, VA
| | - Wolfgang Schima
- Department of Diagnostic and Interventional Radiology, Goettlicher Heiland Krankenhaus, Barmherzige Schwestern Krankenhaus and Sankt Josef Krankenhaus, Vienna, Austria
| | - Shannon P Sheedy
- Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905
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17
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Zhu W, Li X, Zheng G, Bai C, Ji Z, Zhang H, Xing H, Zhang Y, Huo L. Preclinical and pilot clinical evaluation of a small-molecule carbonic anhydrase IX targeting PET tracer in clear cell renal cell carcinoma. Eur J Nucl Med Mol Imaging 2023; 50:3116-3125. [PMID: 37246998 DOI: 10.1007/s00259-023-06248-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 04/24/2023] [Indexed: 05/30/2023]
Abstract
PURPOSE Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. METHODS The in vivo and ex vivo biodistribution of 68Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied. RESULTS NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68Ga-NY104 uptake. CONCLUSION 68Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC. TRIAL REGISTRATION The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023.
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Affiliation(s)
- Wenjia Zhu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Xiaoyuan Li
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Guoyang Zheng
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Zhigang Ji
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Haiqiong Zhang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Haiqun Xing
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China
| | - Yushi Zhang
- Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Li Huo
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.
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18
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Akay S, Pollard JH, Saad Eddin A, Alatoum A, Kandemirli S, Gholamrezanezhad A, Menda Y, Graham MM, Shariftabrizi A. PET/CT Imaging in Treatment Planning and Surveillance of Sinonasal Neoplasms. Cancers (Basel) 2023; 15:3759. [PMID: 37568575 PMCID: PMC10417627 DOI: 10.3390/cancers15153759] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/20/2023] [Accepted: 07/21/2023] [Indexed: 08/13/2023] Open
Abstract
Sinonasal cancers are uncommon malignancies with a generally unfavorable prognosis, often presenting at an advanced stage. Their high rate of recurrence supports close imaging surveillance and the utilization of functional imaging techniques. Whole-body 18F-FDG PET/CT has very high sensitivity for the diagnosis of sinonasal malignancies and can also be used as a "metabolic biopsy" in the characterization of some of the more common subgroups of these tumors, though due to overlap in uptake, histological confirmation is still needed. For certain tumor types, radiotracers, such as 11C-choline, and radiolabeled somatostatin analogs, including 68Ga-DOTATATE/DOTATOC, have proven useful in treatment planning and surveillance. Although serial scans for posttreatment surveillance allow the detection of subclinical lesions, the optimal schedule and efficacy in terms of survival are yet to be determined. Pitfalls of 18F-FDG, such as post-surgical and post-radiotherapy crusting and inflammation, may cause false-positive hypermetabolism in the absence of relapse.
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Affiliation(s)
- Sinan Akay
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Janet H. Pollard
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Assim Saad Eddin
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Aiah Alatoum
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Sedat Kandemirli
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Ali Gholamrezanezhad
- Department of Radiology, Keck School of Medicine, University of Southern California (USC), Los Angeles, CA 90030, USA
| | - Yusuf Menda
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Michael M. Graham
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Ahmad Shariftabrizi
- Division of Nuclear Medicine, Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [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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Purohit K, Minassian G, Purohit L, Peyster R, Bluestone A. Increased Vertebral Gallium-68-DOTATATE Activity on Positron Emission Tomography-Computed Tomography in Merkel Cell Carcinoma: Not Always Metastasis. Cureus 2023; 15:e39427. [PMID: 37362502 PMCID: PMC10288818 DOI: 10.7759/cureus.39427] [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] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Merkel cell carcinoma (MCC) is a rare neuroendocrine dermal malignancy seen in elderly light-skinned individuals, associated with immunosuppression and Merkel cell polyomavirus infection. As a neuroendocrine tumor, the recurrence and metastasis of MCC can be evaluated using positron emission tomography-computed tomography (PET-CT) with the Gallium-68-DOTATATE (Ga-68-DOTATATE) radiotracer, which has demonstrated increased sensitivity to neuroendocrine metastases when compared to F-18 fluorodeoxyglucose (FDG). Here, we present the case of a patient with known metastatic MCC with a new, abnormal focus of increased radiotracer activity in the thoracic spine on Ga-68-DOTATATE PET-CT suspected to represent a metastatic lesion. Further evaluation with MRI revealed a benign vertebral hemangioma, highlighting the limitations of this radiotracer in the setting of benign spinal lesions. Multimodality imaging findings of metastatic MCC and potential pitfalls of Ga-68-DOTATATE PET-CT staging are discussed.
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Affiliation(s)
- Kush Purohit
- Radiology, Stony Brook University Hospital, Stony Brook, USA
| | - Greg Minassian
- Radiology, Stony Brook University Hospital, Stony Brook, USA
| | - Luv Purohit
- Internal Medicine, Broward Health Medical Center, Fort Lauderdale, USA
| | - Robert Peyster
- Radiology, Stony Brook University Hospital, Stony Brook, USA
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21
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Pollard JH, DiCamillo PA, Dundar A, Averill SL, Aswani Y. Gastrointestinal Malignancies. RADIOLOGY‐NUCLEAR MEDICINE DIAGNOSTIC IMAGING 2023:407-455. [DOI: 10.1002/9781119603627.ch14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Kandathil A, Subramaniam RM. Gastroenteropancreatic Neuroendocrine Tumor Diagnosis: DOTATATE PET/CT. PET Clin 2023; 18:189-200. [PMID: 36585339 DOI: 10.1016/j.cpet.2022.11.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Gastroenteropancreatic neuroendocrine tumors(NETs), which arise from the small intestine, rectum, colon, appendix, or pancreas, have variable malignant potential with clinical behavior determined by proliferative activity according to the Ki-67 index and tumor differentiation. Somatostatin receptor (SSTR) expression by NETs allows SSTR imaging using 68Ga-DOTATATE PET/computed tomography (CT) and treatment with octreotide or SSTR-targeted peptide receptor radionuclide therapy (PRRT). 68Ga-DOTATATE PET/CT is indicated for localization of the primary tumor in select cases, staging patients with known NET, and selecting patients for PRRT. NCCN guidelines consider imaging with 68Ga-DOTATATE PET/CT appropriate for staging and receptor status assessment.
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Affiliation(s)
- Asha Kandathil
- Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9316, USA.
| | - Rathan M Subramaniam
- Duke University Medical Center, Department of Radiology, 2301 Erwin Road Box 3808, Durham, NC 27710, USA; Department of Medicine, Otago Medical School, University of Otago, First Floor, Dunedin Hospital, 201 Great King Street, Dunedin 9016, New Zealand
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23
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Kong G, Boehm E, Prall O, Murray WK, Tothill RW, Michael M. Integrating Functional Imaging and Molecular Profiling for Optimal Treatment Selection in Neuroendocrine Neoplasms (NEN). Curr Oncol Rep 2023; 25:465-478. [PMID: 36826704 PMCID: PMC10110720 DOI: 10.1007/s11912-023-01381-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2023] [Indexed: 02/25/2023]
Abstract
PURPOSE OF REVIEW Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges. RECENT FINDINGS In the current era, multidisciplinary management with access to a combination of functional imaging and targeted molecular profiling can provide important disease characterisation, guide individualised management and improve patient outcome. Multiple treatment options are now available, and combination and novel therapies are being explored in clinical trials. Precision medicine is highly relevant for a heterogenous disease like NEN. The integration of dual-tracer functional PET/CT imaging, molecular histopathology and genomic data has the potential to be used to gain a more comprehensive understanding of an individual patient's disease biology for precision diagnosis, prognostication and optimal treatment allocation.
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Affiliation(s)
- Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia. .,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
| | - Emma Boehm
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.,Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia
| | - Owen Prall
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - William K Murray
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Richard W Tothill
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.,Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia
| | - Michael Michael
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.,Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
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24
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D'Souza JC, O'Brien SR, Yang Z, El Jack AK, Pantel AR. Widespread micronodular hepatic metastases of neuroendocrine tumor detected by [68Ga]DOTATATE PET/CT. Radiol Case Rep 2023; 18:481-485. [DOI: 10.1016/j.radcr.2022.10.059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/12/2022] [Accepted: 10/23/2022] [Indexed: 11/25/2022] Open
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Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET. Cancers (Basel) 2023; 15:cancers15020513. [PMID: 36672462 PMCID: PMC9856693 DOI: 10.3390/cancers15020513] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.
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Rectal neuroendocrine neoplasms: what the radiologists should know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4016-4031. [PMID: 35288791 DOI: 10.1007/s00261-022-03474-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023]
Abstract
Neuroendocrine neoplasms of the rectum (R-NENs) are rare; however, their incidence has increased almost threefold in the last few decades. Imaging of R-NENs includes two primary categories: anatomic/morphologic imaging comprised of endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and functional/molecular imaging comprising of planar scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). The management depends on stage, dimension, atypical features, histological grade, and lymphovascular invasion (LVI). Low-risk local R-NENs can be resected endoscopically, and high-risk or locally advanced neoplasms can be treated with radical surgery and lymphadenectomy and/or chemoradiation. The review article focuses on imaging illustrations and discusses applications of different imaging modalities in diagnosing and managing R-NENs.
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van Treijen MJC, Korse CM, Verbeek WH, Tesselaar MET, Valk GD. NETest: serial liquid biopsies in gastroenteropancreatic NET surveillance. Endocr Connect 2022; 11:e220146. [PMID: 35951312 PMCID: PMC9513663 DOI: 10.1530/ec-22-0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 11/27/2022]
Abstract
Objective Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied. Design The study was a longitudinal validation study of serial NETest measurements - a blood-based gene expression signature - in 132 patients with GEPNETs on therapy or watch-and-wait strategy. Methods Serial samples were collected during 46 (range: 6-71) months of follow-up. NETest scores were compared with Response Evaluation Criteria in Solid Tumors version 1.1-defined treatment response (e.g. no evidence of disease (NED), stable disease (SD) or progressive disease (PD)). Results Consecutive NETest scores fluctuated substantially (range: 0-100) over time in individuals with SD (n = 28) and NED (n = 30). Follow-up samples were significantly higher in SD (samples 3-5) and NED subgroups (samples 2-5) compared with baseline results, without changes in imaging. In 82% of untreated patients with PD, consecutive NETest scores consistently remained high. In patients undergoing systemic treatment, the median pre-treatment NETest score in treatment-responders was 76.5 (n = 22) vs 33 (n = 12) in non-responders (P = 0.001). Patients with low pre-treatment scores had 21 months reduced progression-free survival (10 vs 31 months; P = 0.01). The accuracy of the NETest for treatment response prediction was 0.73 (P = 0.009). Conclusion In patients not undergoing treatment, consecutive low NETest scores are associated with indolent behavior. Patients who develop PD exhibit elevated scores. Elevated results have important predictive value for treatment responsiveness and could be used for individualizing decisions on systemic therapy. The clinical value of follow-up NETest scores for patients who choose to watch and wait requires further study.
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Affiliation(s)
- Mark J C van Treijen
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Catharina M Korse
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Clinical Chemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Wieke H Verbeek
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Gastroenterology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Margot E T Tesselaar
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
- Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Center for Neuroendocrine Tumors, ENETS Center of Excellence, Netherlands Cancer Institute, University Medical Center Utrecht, Utrecht, The Netherlands
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Lee ONY, Tan KV, Tripathi V, Yuan H, Chan WWL, Chiu KWH. The Role of 68 Ga-DOTA-SSA PET/CT in the Management and Prediction of Peptide Receptor Radionuclide Therapy Response for Patients With Neuroendocrine Tumors : A Systematic Review and Meta-analysis. Clin Nucl Med 2022; 47:781-793. [PMID: 35485851 DOI: 10.1097/rlu.0000000000004235] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE The aim of this study was to identify and evaluate the role of 68 Ga-DOTA-somatostatin analog (SSA) PET/CT in guiding treatment for patients with neuroendocrine tumors (NETs) based on published literature, with specific focus on the ability of PET/CT to impact clinical management and predict peptide receptor radionuclide therapy (PRRT) response. PATIENTS AND METHODS A systematic literature search of articles up to December 2021 was performed using PubMed and Scopus. Eligible studies included ≥10 patients with confirmed or suspected NETs who had undergone pretreatment staging 68 Ga-DOTA-SSA PET/CT. A meta-analysis using the random-effects model was conducted to determine the overall change in management after PET/CT, whereas PET/CT-derived parameters that correlated with PRRT outcome were summarized from studies that assessed its predictive capabilities. RESULTS A total of 39 studies were included in this systemic review, of which 2266 patients from 24 studies were included for meta-analysis. We showed that PET/CT resulted in a change in clinical management in 36% (95% confidence interval, 31%-41%; range, 3%-66%) of patients. Fifteen studies consisting of 618 patients examined the prognostic ability of 68 Ga-DOTA-SSA PET/CT for PRRT. Of those, 8 studies identified a higher pretreatment SUV to favor PRRT, and 4 identified PET-based radiomic features for somatostatin receptor heterogeneity to be predictive of PRRT response. CONCLUSIONS Along with its diagnostic abilities, 68 Ga-DOTA-SSA PET/CT can impact treatment decision-making and may predict PRRT response in patients with NETs. More robust studies should be conducted to better elucidate the prognostic role of somatostatin receptor PET/CT in optimizing treatment for clinical outcome.
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Affiliation(s)
- Osher Ngo Yung Lee
- From the Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom
| | - Kel Vin Tan
- Department of Oncology, The University of Oxford, Oxford, United Kingdom
| | - Vrijesh Tripathi
- Department of Mathematics and Statistics, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago
| | - Hui Yuan
- Department of Nuclear Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | | | - Keith Wan Hang Chiu
- Department of Diagnostic and Interventional Radiology, Kwong Wah Hospital, Hong Kong
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Fernandes CJ, Leung G, Eads JR, Katona BW. Gastroenteropancreatic Neuroendocrine Tumors. Gastroenterol Clin North Am 2022; 51:625-647. [PMID: 36153114 DOI: 10.1016/j.gtc.2022.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
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Affiliation(s)
- Conrad J Fernandes
- Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Galen Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Jennifer R Eads
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA.
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Agarwal P, Mohamed A. Systemic Therapy of Advanced Well-differentiated Small Bowel Neuroendocrine Tumors Progressive on Somatostatin Analogues. Curr Treat Options Oncol 2022; 23:1233-1246. [PMID: 35939200 DOI: 10.1007/s11864-022-00998-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2022] [Indexed: 11/30/2022]
Abstract
OPINION STATEMENT Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors whose management requires a nuanced and multi-disciplinary approach in order to control symptoms, halt tumor growth, and improve survival outcomes. Of late, the treatment landscape of NENs has advanced considerably as a result of several pivotal clinical trials, which have established somatostatin analogues as first-line therapy for advanced, metastatic, well-differentiated neuroendocrine tumors (NETs). However, an evolving classification system as well as an increased understanding of distinct clinical, molecular, and biologic features contribute to complexity in management. In particular, there remains limited randomized prospective data in the somatostatin analogue (SSA)-refractory setting for patients with primary tumors that originate in the small bowel. For well-differentiated small bowel neuroendocrine tumors (SBNETs), treatment beyond SSAs includes radionuclide therapy, targeted agents, liver-directed therapy, and to a lesser extent, cytotoxic chemotherapy. In the current era, selection of these agents is largely based on expert opinion in the context of patient and tumor characteristics without definitive data on the preferred order of agents to administer. In this review, we aim to describe the treatment landscape of metastatic SBNETs beyond SSAs and provide an overview of novel treatments which are currently under clinical evaluation.
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Affiliation(s)
- Parul Agarwal
- Hematology/Oncology, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, PCAM 10 South Pavilion, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA
| | - Amr Mohamed
- Department of Medical Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Lakeside, Cleveland, OH, 44106, USA.
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31
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Rossi RE, Massironi S. The Increasing Incidence of Neuroendocrine Neoplasms Worldwide: Current Knowledge and Open Issues. J Clin Med 2022; 11:3794. [PMID: 35807078 PMCID: PMC9267138 DOI: 10.3390/jcm11133794] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 06/28/2022] [Indexed: 02/01/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) include a heterogeneous group of tumors derived from neuroendocrine cells, most commonly arising from the gastro-entero-pancreatic (GEP) and bronchopulmonary tracts [...].
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Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Sara Massironi
- Division of Gastroenterology, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy;
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Muros MA, Aroui T, Rivas-Navas D, Fernandez-Fernadez J. Integration of molecular imaging in the personalized approach to neuroendocrine tumors. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2022; 66:116-129. [PMID: 35238519 DOI: 10.23736/s1824-4785.22.03431-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
NETs lesions can be difficult to characterize with conventional anatomic imaging (CT and MRI). Functional imaging techniques, and especially PET imaging, are very useful for detecting small neuroendocrine tumors that would not be seen with other techniques. The role of nuclear medicine in the localization, staging, restaging, treatment and monitoring of neuroendocrine tumors (NETs) has become progressively more relevant due to: the availability of tracers on new targets, tracers for positron emission tomography (PET); the development of cyclotrons and generators that allow this availability; as well as to hybrid systems (SPECT/CT, PET/CT and PET/MRI) that, by joining the functional and anatomical image, improve the quality of the images. Teragnosis, a new emerging therapy, in NET used receptor-mediated or nonreceptor- mediated mechanism to facilitate penetration and high-affinity binding between the radiopharmaceutical and the tumor cell. Teragnosis offers the possibility of personalized targeted radionuclide therapy.
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Affiliation(s)
- Maria A Muros
- Department of Nuclear Medicine, Virgen de las Nieves Hospital, Granada, Spain -
| | - Tarik Aroui
- Department of Nuclear Medicine, Virgen de las Nieves Hospital, Granada, Spain
| | - Daniel Rivas-Navas
- Department of Nuclear Medicine, Virgen de las Nieves Hospital, Granada, Spain
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Magi L, Prosperi D, Lamberti G, Marasco M, Ambrosini V, Rinzivillo M, Campana D, Gentiloni G, Annibale B, Signore A, Panzuto F. Role of [ 18F]FDG PET/CT in the management of G1 gastro-entero-pancreatic neuroendocrine tumors. Endocrine 2022; 76:484-490. [PMID: 35149933 PMCID: PMC9068639 DOI: 10.1007/s12020-022-03000-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 01/28/2022] [Indexed: 02/08/2023]
Abstract
PURPOSE Since the role of [18F]FDG PET/CT in low-grade gastroenteropancreatic (GEP) neuroendocrine neoplasia (NET) is not well established, this study was aimed to evaluate the role of [18F]FDG PET/CT in grade 1 (G1) GEP-NETs. METHODS This is a retrospective study including patients with G1 GEP-NETs who underwent [18F]FDG PET/CT. RESULTS 55 patients were evaluated, including 24 (43.6%) with pancreatic NETs and 31 (56.4%) with gastrointestinal NETs. At the time of diagnosis, 28 (51%) patients had metastatic disease, and 50 (91%) patients were positive by 68-Ga sstr PET/CT. Overall, 27 patients (49%) had positive findings on [18F]FDG PET/CT. Following [18F]FDG PET/CT, therapeutic management was modified in 29 (52.7%) patients. Progression-free survival was longer in patients with negative [18F]FDG PET/CT compared with positive [18F]FDG PET/CT (median PFS was not reached and 24 months, respectively, p = 0.04). This significance was particularly evident in the pancreatic group (p = 0.008). CONCLUSIONS Despite having low proliferative activity, approximately half of GEP-NETs G1 showed positive [18F]FDG PET/CT, with a corresponding negative impact on patients' clinical outcomes. These data are in favor of a more "open" attitude toward the potential use of [18F]FDG PET/CT in the diagnostic work-up of G1 GEP-NETs, which may be used in selected cases to detect those at higher risk for an unfavorable disease course.
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Affiliation(s)
- Ludovica Magi
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniela Prosperi
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189, Rome, Italy
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Marasco
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
| | - Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Guido Gentiloni
- Nuclear Medicine Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, 00189, Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, 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, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, 00189, Rome, Italy.
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
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Galgano SJ, Iravani A, Bodei L, El-Haddad G, Hofman MS, Kong G. Imaging of Neuroendocrine Neoplasms: Monitoring Treatment Response- AJR Expert Panel Narrative Review. AJR Am J Roentgenol 2022; 218:767-780. [PMID: 34985313 DOI: 10.2214/ajr.21.27159] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Neuroendocrine neoplasms (NENs) encompass a broad spectrum of tumors throughout the body and range in biologic behavior from indolent to aggressive. Consequently, a wide spectrum of treatment options are available for NENs, including observation, somatostatin analogues, targeted therapy, chemotherapy, surgical resection, liver-directed therapy (embolization and ablation), and peptide receptor radionuclide therapy. Given the wide variety of tumor behaviors and treatments, precise criteria for treatment response in NENs are lacking. Though conventional anatomic imaging with CT and MRI remains important for NEN response assessment, the use of somatostatin receptor (SSR) PET is increasing and often provides synergistic and complementary information. Additionally, in certain clinical scenarios, a particular imaging strategy may prove superior or inferior to others for the detection of metastatic disease and evaluation of therapy response. A strong need exists to further define appropriate and standardized assessment criteria for tumor response and progression in NEN. This article presents the strengths and weaknesses of individual imaging modalities for evaluating NEN therapy response, including conventional anatomic imaging, SSR PET, FDG PET, dual-tracer PET, and PET/MRI. Ongoing challenges and unmet needs in the use of imaging for NEN response evaluation are explored.
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Affiliation(s)
- Samuel J Galgano
- Department of Radiology, University of Alabama at Birmingham, 619 19th St S, JT N325, Birmingham, AL 35249
| | - Amir Iravani
- Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO
| | - Lisa Bodei
- Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, FL
| | - Michael S Hofman
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
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Kersting D, Settelmeier S, Mavroeidi IA, Herrmann K, Seifert R, Rischpler C. Shining Damaged Hearts: Immunotherapy-Related Cardiotoxicity in the Spotlight of Nuclear Cardiology. Int J Mol Sci 2022; 23:3802. [PMID: 35409161 PMCID: PMC8998973 DOI: 10.3390/ijms23073802] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/20/2022] [Accepted: 03/25/2022] [Indexed: 11/30/2022] Open
Abstract
The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term complications in terms of cardiomyopathy, arrythmia, and vascular disease. In cancer patients and, particularly, cancer patients undergoing (immune-)therapy, cardio-oncological monitoring is a complex interplay between pretherapeutic risk assessment, identification of impending cardiotoxicity, and post-therapeutic surveillance. For these purposes, the cardio-oncologist can revert to a broad spectrum of nuclear cardiological diagnostic workup. The most promising commonly used nuclear medicine imaging techniques in relation to immunotherapy will be discussed in this review article with a special focus on the continuous development of highly specific molecular markers and steadily improving methods of image generation. The review closes with an outlook on possible new developments of molecular imaging and advanced image evaluation techniques in this exciting and increasingly growing field of immunotherapy-related cardiotoxicity.
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Affiliation(s)
- David Kersting
- Department of Nuclear Medicine, University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, 45147 Essen, Germany; (K.H.); (R.S.); (C.R.)
- German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), 45147 Essen, Germany;
| | - Stephan Settelmeier
- Department of Cardiology and Vascular Medicine, University Hospital Essen, West German Heart and Vascular Center, University of Duisburg-Essen, 45147 Essen, Germany;
| | - Ilektra-Antonia Mavroeidi
- German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), 45147 Essen, Germany;
- Clinic for Internal Medicine (Tumor Research), University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, 45147 Essen, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, 45147 Essen, Germany; (K.H.); (R.S.); (C.R.)
- German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), 45147 Essen, Germany;
| | - Robert Seifert
- Department of Nuclear Medicine, University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, 45147 Essen, Germany; (K.H.); (R.S.); (C.R.)
- German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), 45147 Essen, Germany;
| | - Christoph Rischpler
- Department of Nuclear Medicine, University Hospital Essen, West German Cancer Center (WTZ), University of Duisburg-Essen, 45147 Essen, Germany; (K.H.); (R.S.); (C.R.)
- German Cancer Consortium (DKTK, Partner Site Essen/Düsseldorf), 45147 Essen, Germany;
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Ambrosini V, Zanoni L, Filice A, Lamberti G, Argalia G, Fortunati E, Campana D, Versari A, Fanti S. Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors. Cancers (Basel) 2022; 14:1055. [PMID: 35205805 PMCID: PMC8870358 DOI: 10.3390/cancers14041055] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/10/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.
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Affiliation(s)
- Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Lucia Zanoni
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Angelina Filice
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Giulia Argalia
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Emilia Fortunati
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Stefano Fanti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
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McClenathan M, Peacock JG. The "Ultimate Triple PET": 68Ga-DOTATATE, 18F-FDG, and 18F-Fluciclovine PET/CT Findings in a Single Patient With Metastatic Abdominal Carcinoid and Prostate Cancer. Clin Nucl Med 2022; 47:e161-e164. [PMID: 34392283 DOI: 10.1097/rlu.0000000000003853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
ABSTRACT A 71-year-old man with a history of carcinoid and prostate adenocarcinoma underwent 68Ga-DOTATATE PET/CT to evaluate new mediastinal lymphadenopathy. The scan revealed new carcinoid metastases, but the mediastinal nodes were not avid. 18F-FDG PET/CT was performed to evaluate for cardiac and mediastinal sarcoidosis, revealing a lack of cardiac sarcoidosis, but probable mediastinal sarcoidosis. 18F-Fluciclovine PET/CT was then performed for possible prostate metastases, revealing the patient's known prostate cancer. Three different PET radiopharmaceuticals revealed 3 different processes in a single patient within a 195-day period, demonstrating the power of nuclear medicine diagnostics.
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Affiliation(s)
- Matthew McClenathan
- From the Department of Radiology, Brooke Army Medical Center, San Antonio, TX
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Cavicchioli M, Bitencourt AGV, Lima ENP. 68Ga-DOTATATE PET/CT versus 111In-octreotide scintigraphy in patients with neuroendocrine tumors: a prospective study. Radiol Bras 2022; 55:13-18. [PMID: 35210659 PMCID: PMC8864693 DOI: 10.1590/0100-3984.2021.0038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/11/2021] [Indexed: 01/15/2023] Open
Abstract
Objective To compare 68Ga-DOTA-DPhe1,Tyr3-octreotate
(68Ga-DOTATATE) positron-emission tomography/computed tomography
(PET/CT) findings with those of conventional 111In-octreotide
scintigraphy in patients with neuroendocrine tumors (NETs). Materials and Methods This was a single-center prospective study including 41 patients (25 males;
mean age, 55.4 years) with biopsy-proven NETs who underwent whole-body
111In-octreotide scintigraphy and whole-body
68Ga-DOTATATE PET/CT. The patients had been referred for tumor
staging (34.1%), tumor restaging (61.0%), or response evaluation (4.9%).
Images were compared in a patient-by-patient analysis to identify additional
lesions, and we attempted to determine the impact that discordant findings
had on treatment planning. Results Compared with 111In-octreotide scintigraphy,
68Ga-DOTATATE PET/CT revealed more lesions, the additional
lesions typically being in the liver or bowel. Changes in management owing
to the additional information provided by 68Ga-DOTATATE PET/CT
occurred in five patients (12.2%), including intermodal changes in three
(7.3%) and intramodal changes in two (4.9%). In addition,
68Ga-DOTATATE PET/CT yielded incidental findings unrelated to the
primary NET in three patients (7.3%): Hürthle cell carcinoma of the
thyroid, bowel non-Hodgkin lymphoma, and a suspicious breast lesion. Conclusion We conclude that 68Ga-DOTATATE PET/CT is superior to conventional
111In-octreotide scintigraphy for the management of NETs
because of its ability to determine the extent of the disease more
accurately, which, in some cases, translates to changes in the treatment
plan.
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39
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Fanti S, Ambrosini V. PET Imaging in Neuro-Endocrine Neoplasms (NEN). Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00034-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Rossi RE, Elvevi A, Citterio D, Coppa J, Invernizzi P, Mazzaferro V, Massironi S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol 2021; 27:5890-5907. [PMID: 34629807 PMCID: PMC8475006 DOI: 10.3748/wjg.v27.i35.5890] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/29/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20122, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
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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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Jayaprakasam VS, Paroder V, Schöder H. Variants and Pitfalls in PET/CT Imaging of Gastrointestinal Cancers. Semin Nucl Med 2021; 51:485-501. [PMID: 33965198 PMCID: PMC8338802 DOI: 10.1053/j.semnuclmed.2021.04.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In the past two decades, PET/CT has become an essential modality in oncology increasingly used in the management of gastrointestinal (GI) cancers. Most PET/CT tracers used in clinical practice show some degree of GI uptake. This uptake is quite variable and knowledge of common patterns of biodistribution of various radiotracers is helpful in clinical practice. 18F-Fluoro-Deoxy-Glucose (FDG) is the most commonly used radiotracer and has quite a variable uptake within the bowel. 68Ga-Prostate specific membrane antigen (PSMA) shows intense uptake within the proximal small bowel loops. 11C-methyl-L-methionine (MET) shows high accumulation within the bowels, which makes it difficult to assess bowel or pelvic diseases. One must also be aware of technical artifacts causing difficulties in interpretations, such as high attenuation oral contrast material within the bowel lumen or misregistration artifact due to patient movements. It is imperative to know the common variants and benign diseases that can mimic malignant pathologies. Intense FDG uptake within the esophagus and stomach may be a normal variant or may be associated with benign conditions such as esophagitis, reflux disease, or gastritis. Metformin can cause diffuse intense uptake throughout the bowel loops. Intense physiologic uptake can also be seen within the anal canal. Segmental bowel uptake can be seen in inflammatory bowel disease, radiation, or medication induced enteritis/colitis or infection. Diagnosis of appendicitis or diverticular disease requires CT correlation, as normal appendix or diverticulum can show intense uptake. Certain malignant pathologies are known to have only low FDG uptake, such as early-stage esophageal adenocarcinoma, mucinous tumors, indolent lymphomas, and multicystic mesotheliomas. Response assessment, particularly in the neoadjuvant setting, can be limited by post-treatment inflammatory changes. Post-operative complications such as abscess or fistula formation can also show intense uptake and may obscure underlying malignant pathology. In the absence of clinical suspicion or rising tumor marker, the role of FDG PET/CT in routine surveillance of patients with GI malignancy is not clear.
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Affiliation(s)
- Vetri Sudar Jayaprakasam
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Viktoriya Paroder
- Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Heiko Schöder
- Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY.
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43
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Ratnayake GM, Luong TV, Toumpanakis C, Caplin M, Grossman AB. Middle ear neuroendocrine tumours: Insight into their pathogenesis, diagnosis and management. J Neuroendocrinol 2021; 33:e13031. [PMID: 34462974 DOI: 10.1111/jne.13031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 07/13/2021] [Accepted: 08/10/2021] [Indexed: 11/29/2022]
Abstract
Recent advances in the diagnosis of neuroendocrine tumours (NETs) have led to the identification of NETs in unusual locations. NETs originating in the middle ear have been reported in a number of case reports with differing terminologies, where they were variously referred to as middle ear adenomas or middle ear carcinoids. In this report, we describe two cases of middle ear NETs with locally advanced disease and with distant metastases, respectively. The embryological origin, pathogenesis and histopathological characteristics, including immunohistochemical markers, are discussed aiming to clarify the terminology of these tumours. Functional imaging modalities (eg, 68 Ga-DOTATATE positron emission tomography/computed tomography/magnetic resonance imaging) play a pivotal role in the diagnosis, staging and determining the optimal systemic therapy in managing NETs of the middle ear. In addition, surgical, local and systemic therapeutic modalities are discussed, including the management option of long-acting somatostatin analogue therapy and targeted radionuclide therapy for somatostatin receptor-positive well-differentiated middle ear NETs.
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Affiliation(s)
- Gowri M Ratnayake
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Tu Vinh Luong
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Christos Toumpanakis
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Martyn Caplin
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Ashley B Grossman
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
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Ga-68 DOTATATE PET/CT and F-18 FDG PET/CT in the evaluation of low and intermediate versus high-grade neuroendocrine tumors. Nucl Med Commun 2021; 41:1060-1065. [PMID: 32732600 DOI: 10.1097/mnm.0000000000001255] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE We investigated the role of Ga-68 DOTATATE PET/CT in comparison to F-18 FDG PET/CT in patients with low and intermediate versus high-grade neuroendocrine tumors (NETs). METHODS We identified 81 patients who underwent Ga-68 DOTATATE PET/CT at our institution between May 2017 and December 2018 and met inclusion criteria of biopsy-proven NET with known Ki-67 index, histologic grade, or differentiation. Patients were divided into two groups. Control group included Ki-67 ≤20%, grade 1 or 2, or well-differentiated tumors. Experimental group included Ki-67 >20%, grade 3, or poorly-differentiated tumors. RESULTS Mean age was 57 years, with 36 males and 45 females. Most common primary sites were small bowel, pancreas, and lung. Most common distant metastatic sites were liver and bone. In the control group (n = 67), median Ki-67 was 4% (range 1-30%). 55/67 (82.1%) DOTATATE and 6/11 (54.5%) FDG scans were positive (P = 0.04). Positive scans showed >10 lesions in 25/55 (45.5%) DOTATATE and 1/6 (16.7%) FDG scans (P = 0.18). 40/55 (72.7%) positive DOTATATE and 3/6 (50%) FDG scans showed distant disease (P = 0.25). In the experimental group (n = 14), median Ki-67 was 68% (range 25-95%). All 14 DOTATATE and all nine FDG scans were positive. Positive scans showed >10 lesions in 4/14 (28.6%) DOTATATE and 5/9 (55.6%) FDG scans (P = 0.20). 10/14 (71.4%) positive DOTATATE and 7/9 (77.8%) FDG scans showed distant disease (P = 0.74). CONCLUSION All patients with high grade, poorly-differentiated NETs had positive DOTATATE PET/CTs. In these patients, DOTATATE PET/CT did not significantly differ from FDG PET/CT in identifying >10 lesions or distant disease.
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Pirasteh A, Lovrec P, Pedrosa I. Imaging and its Impact on Defining the Oligometastatic State. Semin Radiat Oncol 2021; 31:186-199. [PMID: 34090645 DOI: 10.1016/j.semradonc.2021.03.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Successful treatment of oligometastatic disease (OMD) is facilitated through timely detection and localization of disease, both at the time of initial diagnosis (synchronous OMD) and following the initial therapy (metachronous OMD). Hence, imaging plays an indispensable role in management of patients with OMD. However, the challenges and complexities of OMD management are also reflected in the imaging of this entity. While innovations and advances in imaging technology have made a tremendous impact in disease detection and management, there remain substantial and unaddressed challenges for earlier and more accurate establishment of OMD state. This review will provide an overview of the available imaging modalities and their inherent strengths and weaknesses, with a focus on their role and potential in detection and evaluation of OMD in different organ systems. Furthermore, we will review the role of imaging in evaluation of OMD for malignancies of various primary organs, such as the lung, prostate, colon/rectum, breast, kidney, as well as neuroendocrine tumors and gynecologic malignancies. We aim to provide a practical overview about the utilization of imaging for clinicians who play a role in the care of those with, or at risk for OMD.
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Affiliation(s)
- Ali Pirasteh
- Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, WI
| | - Petra Lovrec
- Department of Radiology, University of Wisconsin-Madison, Madison, WI
| | - Ivan Pedrosa
- Departments of Radiology, Urology, and Advanced Imaging Research Center. University of Texas Southwestern, Dallas, TX.
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Steinkraus K, Andresen JR, Clift AK, Liedke MO, Frilling A. Multifocal neuroendocrine tumour of the small bowel presenting as an incarcerated incisional hernia: a surgical challenge in a high-risk patient. J Surg Case Rep 2021; 2021:rjab219. [PMID: 34150191 PMCID: PMC8208802 DOI: 10.1093/jscr/rjab219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/04/2021] [Accepted: 05/06/2021] [Indexed: 11/25/2022] Open
Abstract
Neuroendocrine tumours (NET) of the small bowel present significant clinical challenges, such as their rate of metastasis at initial presentation, common multifocality and understaging even with gold standard imaging. Here, we present a case of a high-risk surgical patient with a complex medical history initially presenting as an acute abdomen due to an incarcerated incisional hernia. He was found at emergency laparotomy to have three small NET deposits in a 30-cm segment of incarcerated ileum which was resected. Postoperative morphological and functional imaging and biochemical markers were unremarkable, but due to clinical suspicion for undetected residual tumour bulk given the non-systematic palpation of the entire small bowel at initial operation, underwent re-operation where a further 70 cm of ileum was found to harbour multiple tumour deposits (n = 25) and was resected. There was no surgical morbidity and the patient remains tumour-free at 9-month follow-up.
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Affiliation(s)
| | | | - Ashley K Clift
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Marc O Liedke
- Department of Visceral, Thoracic, and Vascular Surgery, Westkuestenkliniken, Heide Germany
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
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Kong G, Hicks R. Radionuclide imaging of NENs. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 18:207-215. [DOI: 10.1016/j.coemr.2021.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Hu Y, Ye Z, Wang F, Qin Y, Xu X, Yu X, Ji S. Role of Somatostatin Receptor in Pancreatic Neuroendocrine Tumor Development, Diagnosis, and Therapy. Front Endocrinol (Lausanne) 2021; 12:679000. [PMID: 34093445 PMCID: PMC8170475 DOI: 10.3389/fendo.2021.679000] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/27/2021] [Indexed: 12/02/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare and part of the diverse family of neuroendocrine neoplasms (NENs). Somatostatin receptors (SSTRs), which are widely expressed in NENs, are G-protein coupled receptors that can be activated by somatostatins or its synthetic analogs. Therefore, SSTRs have been widely researched as a diagnostic marker and therapeutic target in pNETs. A large number of studies have demonstrated the clinical significance of SSTRs in pNETs. In this review, relevant literature has been appraised to summarize the most recent empirical evidence addressing the clinical significance of SSTRs in pNETs. Overall, these studies have shown that SSTRs have great value in the diagnosis, treatment, and prognostic prediction of pNETs; however, further research is still necessary.
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Affiliation(s)
- Yuheng Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Zeng Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Fei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
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49
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Dimopoulos YP, Winslow ER, He AR, Ozdemirli M. Hepatocellular carcinoma with biliary and neuroendocrine differentiation: A case report. World J Clin Oncol 2021; 12:262-271. [PMID: 33959479 PMCID: PMC8085510 DOI: 10.5306/wjco.v12.i4.262] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/07/2021] [Accepted: 03/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver tumors with dual differentiations [combined hepatocellular carcinoma (HCC) and cholangiocarcinoma] are common. However, liver tumors that exhibit hepatocellular, biliary, and neuroendocrine differentiation are exceedingly rare, with only three previous case reports in the literature.
CASE SUMMARY A 65-year-old female with a previous history of hepatitis C and a distant history of low grade, well-differentiated rectal neuroendocrine tumor was found to have two liver lesions in segment 4 and segment 7 on imaging. Serum alpha-fetoprotein and chromogranin A were elevated. Biopsy of the larger lesion in segment 4 revealed a high-grade tumor, with morphologic and immunohistochemical features of a neuroendocrine tumor. Given the previous history of rectal neuroendocrine tumor, imaging investigation, serologic markers, and biopsy findings, metastatic neuroendocrine tumor was considered. Subsequent regional resection of these hepatic lesions revealed the segment 4 lesion to be a HCC with additional biliary and neuroendocrine differentiation and the segment 7 lesion to be a cholangiocarcinoma with neuroendocrine differentiation. Follow-up of the patient revealed disease recurrence in the dome of the liver and metastasis in retro-pancreatic lymph nodes. The patient eventually expired due to complications of chemotherapy.
CONCLUSION HCC cases with additional biliary and neuroendocrine differentiation are exceedingly rare, posing a diagnostic challenge for clinicians and pathologists.
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Affiliation(s)
- Yiannis Petros Dimopoulos
- Department of Pathology and Laboratory Medicine, Medstar Georgetown University Hospital, Washington, DC 20007, United States
| | - Emily R Winslow
- Medstar Center for Liver and Pancreas Surgery, Medstar Georgetown University Hospital, Washington, DC 20007, United States
| | - Aiwu Ruth He
- Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC 20007, United States
| | - Metin Ozdemirli
- Department of Pathology and Laboratory Medicine, Medstar Georgetown University Hospital, Washington, DC 20007, United States
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50
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Liu KY, Goldrich DY, Ninan SJ, Filimonov A, Lam H, Govindaraj S, Iloreta AM. The value of 68 Gallium-DOTATATE PET/CT in sinonasal neuroendocrine tumor management: A case series. Head Neck 2021; 43:E30-E40. [PMID: 33786927 DOI: 10.1002/hed.26695] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 02/25/2021] [Accepted: 03/16/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND 68 Gallium-DOTATATE (68 Ga-DOTATATE) is a somatostatin analog used as a PET tracer to successfully identify neuroendocrine tumors (NETs). Due to the rarity of sinonasal NETs, there are few recommendations for 68 Ga-DOTATATE imaging in these patients. METHODS We discussed the impact of 68 Ga-DOTATATE imaging on the management of six sinonasal NET cases and reviewed existing literature. RESULTS 68 Ga-DOTATATE PET/CT revealed an unknown primary in one case and identified metastatic disease in a primary sinonasal small cell neuroendocrine carcinoma (SNEC) patient missed on conventional imaging. In two esthesioneuroblastoma (ENB) patients, 68 Ga-DOTATATE detected abnormal radiotracer uptake not present on 18F-FDG PET/CT and identified a patient for treatment with 177 Lu-DOTATATE. CONCLUSIONS This is the one of the first few reports, and the largest series to our knowledge, demonstrating the utility of 68 Ga-DOTATATE imaging for primary sinonasal SNEC and ENB. Further study is required to determine its role in sinonasal NET management.
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Affiliation(s)
- Katherine Y Liu
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - David Y Goldrich
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Sen J Ninan
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Andrey Filimonov
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Hansen Lam
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Satish Govindaraj
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Alfred Marc Iloreta
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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