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Evans MG, Xiu J, Darabi S, Crymes A, Bedeir A, Bryant DA, Oberley MJ, Demeure MJ. Loss of O6-Methylguanine-DNA Methyltransferase Protein Expression by Immunohistochemistry Is Associated With Response to Capecitabine and Temozolomide in Neuroendocrine Neoplasms. World J Surg 2025; 49:964-972. [PMID: 39825572 PMCID: PMC11994148 DOI: 10.1002/wjs.12471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 12/03/2024] [Accepted: 12/15/2024] [Indexed: 01/20/2025]
Abstract
BACKGROUND A recent prospective phase II study (ECOG-ACRIN E2211) demonstrated that MGMT deficiency was associated with a significant response to capecitabine and temozolomide (CAPTEM) in pancreatic neuroendocrine neoplasms (NENs); however, routine MGMT analysis in NENs was not recommended. Our study sought to demonstrate whether loss of MGMT protein expression is associated with improved overall survival (OS) in patients receiving CAPTEM for NENs from various tumor sites. MATERIALS AND METHODS Paraffin-embedded tumor samples were evaluated by immunohistochemistry (IHC) using an MGMT monoclonal antibody. Intact MGMT protein expression (i.e., IHC positivity) was defined as any staining intensity (> 1+) in ≥ 36% of neoplastic cells according to an internal validation study. IHC and pyrosequencing for MGMT promotor methylation was performed in an independent cohort of 58 NENs. Real-world OS was extrapolated from insurance claims data with Kaplan-Meier estimates from the date of first CAPTEM administration to the last date of contact. RESULTS The study cohort included 80 patients (42 men and 38 women) with a median age of 57 years (range: 19-89). They had various NENs (33 pancreatic, 17 intestinal, 7 pulmonary, 8 other, and 15 of unknown origin) treated with CAPTEM. The median OS for the 48 patients with MGMT negative tumors was 31 months compared to 17.5 months for the 32 patients whose tumors were MGMT positive by IHC (HR: 1.75 [95% CI: 1.066-2.87] and p = 0.025). IHC results from the independent cohort of 58 NENs showed only 57% concordance with pyrosequencing results. CONCLUSIONS MGMT promotor status by IHC may be a clinically useful indicator that predicts improved OS for NENs treated with CAPTEM, but IHC does not reliably correlate with the findings of MGMT promoter methylation by pyrosequencing.
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Affiliation(s)
- Mark G. Evans
- Departments of Pathology and Clinical and Translational ResearchCaris Life SciencesPhoenixArizonaUSA
| | - Joanne Xiu
- Departments of Pathology and Clinical and Translational ResearchCaris Life SciencesPhoenixArizonaUSA
| | - Sourat Darabi
- Precision Medicine ProgramHoag Family Cancer InstituteNewport BeachCaliforniaUSA
| | - Anthony Crymes
- Department of Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCaliforniaUSA
| | | | - David A. Bryant
- Departments of Pathology and Clinical and Translational ResearchCaris Life SciencesPhoenixArizonaUSA
| | - Matthew J. Oberley
- Departments of Pathology and Clinical and Translational ResearchCaris Life SciencesPhoenixArizonaUSA
| | - Michael J. Demeure
- Precision Medicine ProgramHoag Family Cancer InstituteNewport BeachCaliforniaUSA
- Translational Genomics Research InstitutePhoenixArizonaUSA
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2
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Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Hematol Oncol Clin North Am 2025; 39:37-53. [PMID: 39510676 DOI: 10.1016/j.hoc.2024.08.001] [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: 11/15/2024]
Abstract
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.
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Affiliation(s)
- Catherine G Tran
- Department of Surgery, Division of Colorectal Surgery, University of Minnesota, Minneapolis, MN
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | | | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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3
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Popa SG, Golli AL, Matei CF, Sonei AN, Vere C, Cimpeanu R, Munteanu M, Munteanu A. Pancreatic Neuroendocrine Tumors-Diagnostic Pitfalls of Non-Diabetic Severe Hypoglycemia: Literature Review and Case Report. Diagnostics (Basel) 2025; 15:337. [PMID: 39941267 PMCID: PMC11816404 DOI: 10.3390/diagnostics15030337] [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: 12/02/2024] [Revised: 01/23/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Hypoglycemia in the case of persons without diabetes is a rare event, being usually, initially misinterpreted based on the symptoms that can mimic various diseases, especially of a neuro-psychiatric nature. In the case of the identification of insulin-mediated hypoglycemia, the evaluation of pancreatic neuroendocrine tumors, which represent the most common and worrisome causes of non-diabetic insulin-mediated hypoglycemia, must be considered. Case Report: We present the case of a 57-year-old patient, hospitalized for a history of approximately one month of recurrent episodes of symptoms suggestive for severe hypoglycemia. The biological evaluation performed during an episode of hypoglycemia showed a plasma glucose value of 44 mg/dL, insulinemia 16.3 µU/mL, C peptide 3.72 ng/mL, HbA1c 4.99%, absence of urinary ketone bodies and anti-insulin antibodies <0.03 U/mL. The CT and MRI examination showed a 15.3/15 mm rounded tumor in the pancreatic corporeo-caudal region. The pancreatic tumor formation was enucleated and the histopathological and immunohistochemical analysis confirmed the diagnosis of the pancreatic neuroendocrine tumor with a positive reaction for chromogranin A, synaptophysin and insulin, without malignancy features (Ki 67 positive in 1% of the tumor cells). The postoperative evolution was favorable, without episodes of hypoglycemia, the fasting insulinemia one day after surgery being 4.1 µU/mL and HbA1c at three weeks postoperatively being 5.51%. Conclusions: The management of patients with hyperinsulinemic hypoglycemia secondary to insulinoma involves multidisciplinary collaboration with an important role in recognizing symptoms suggestive of hypoglycemia in a person without diabetes, initiating biological and imaging evaluation, establishing the optimal therapeutic option and histopathological confirmation.
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Affiliation(s)
- Simona Georgiana Popa
- Department of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy, 200349 Craiova, Romania;
| | - Andreea Loredana Golli
- Department of Public Health and Healthcare Management, University of Medicine and Pharmacy, 200349 Craiova, Romania
| | - Cristina Florentina Matei
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Hospital, 200642 Craiova, Romania; (C.F.M.); (A.N.S.)
| | - Alexandra Nicoleta Sonei
- Department of Diabetes, Nutrition and Metabolic Diseases, Emergency County Hospital, 200642 Craiova, Romania; (C.F.M.); (A.N.S.)
| | - Cristin Vere
- Department of Gastroenterology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.V.); (R.C.)
| | - Radu Cimpeanu
- Department of Gastroenterology, University of Medicine and Pharmacy, 200349 Craiova, Romania; (C.V.); (R.C.)
| | - Marian Munteanu
- Department of Surgery, University of Medicine and Pharmacy, 200349 Craiova, Romania; (M.M.); (A.M.)
| | - Alexandru Munteanu
- Department of Surgery, University of Medicine and Pharmacy, 200349 Craiova, Romania; (M.M.); (A.M.)
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4
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Liu M, Yan X, Lin X, Chen L, Wang Y, Luo Y, Lin Y, He Q, Chen J, Zhang N. Efficacy, safety, and prognostic factors of capecitabine plus temozolomide regimen in patients with atypical thymic carcinoids. Ther Adv Med Oncol 2024; 16:17588359241297578. [PMID: 39610443 PMCID: PMC11603466 DOI: 10.1177/17588359241297578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/18/2024] [Indexed: 11/30/2024] Open
Abstract
Background and objectives Atypical thymic carcinoids (ATCs) are rare mediastinal malignancies that lack established treatment guidelines. Capecitabine and temozolomide (CapTem) has demonstrated significant efficacy in pancreatic neuroendocrine neoplasms (NENs), while its applicability and effectiveness in ATCs remain underexplored. This study seeks to investigate the efficacy, safety, and prognostic factors associated with CapTem in ATC patients. Design and methods Thirty-eight ATC patients treated with CapTem at our center were analyzed. We assessed the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects. We also examined patients' clinicopathological characteristics and their correlations with CapTem efficacy. Results The cohort achieved a 15.8% ORR and 89.5% DCR, with a median PFS of 13.0 months. Multivariate analysis identified the platelet-to-lymphocyte ratio (PLR) as a significant independent prognostic factor for PFS, with a PLR ⩾ 235 associated with shorter PFS (7 months vs. undefined, p = 0.0004). Age was an independent prognostic factor for OS, with patients over 50 years experiencing shorter OS (36 months vs. undefined, p = 0.015). Safety analysis showed rare severe toxicities and no treatment-related fatalities. Conclusion CapTem is an effective and well-tolerated treatment for ATC patients. Pretreatment PLR and age appear to be potential prognostic markers for CapTem therapy; however, these results warrant validation in larger patient cohorts.
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Affiliation(s)
- Man Liu
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xu Yan
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoxuan Lin
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Luohai Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanji Luo
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yuan Lin
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiao He
- Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, No.270 Dongan Road, Xuhui District, Shanghai, China
| | - Ning Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangdong Province, Guangzhou, China
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5
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Jiang J, Xu J, Ji S, Yu X, Chen J. Unraveling the mysteries of MGMT: Implications for neuroendocrine tumors. Biochim Biophys Acta Rev Cancer 2024; 1879:189184. [PMID: 39303858 DOI: 10.1016/j.bbcan.2024.189184] [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: 01/28/2024] [Revised: 07/15/2024] [Accepted: 09/16/2024] [Indexed: 09/22/2024]
Abstract
Neuroendocrine tumors (NETs) are a diverse group of tumors that arise from neuroendocrine cells and are commonly found in various organs. A considerable proportion of NET patients were diagnosed at an advanced or metastatic stage. Alkylating agents are the primary treatment for NET, and O6-methylguanine methyltransferase (MGMT) remains the first-line of defense against DNA damage caused by these agents. Clinical trials have indicated that MGMT promoter methylation or its low/lacked expression can predict a favorable outcome with Temozolomide in NETs. Its status could help select NET patients who can benefit from alkylating agents. Therefore, MGMT status serves as a biomarker to guide decisions on the efficacy of Temozolomide as a personalized treatment option. Additionally, delving into the regulatory mechanisms of MGMT status can lead to the development of MGMT-targeted therapies, benefiting individuals with high levels of MGMT expression. This review aims to explore the polymorphism of MGMT regulation and summarize its clinical implications in NETs, which would help establish the role of MGMT as a biomarker and its potential as a therapeutic target in NETs. Additionally, we explore the benefits of combining Temozolomide and immunotherapy in MGMT hypermethylated subgroups. Future studies can focus on optimizing Temozolomide administration to induce specific immunomodulatory changes.
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Affiliation(s)
- Jianyun Jiang
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Junfeng Xu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
| | - Shunrong Ji
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
| | - Xianjun Yu
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
| | - Jie Chen
- Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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6
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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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7
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Daoud T, Morani AC, Waters R, Bhosale P, Virarkar MK. Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site. J Comput Assist Tomogr 2024; 48:588-600. [PMID: 37876246 DOI: 10.1097/rct.0000000000001548] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Abstract
ABSTRACT Neuroendocrine tumors (NETs) are relatively uncommon heterogeneous neoplasms arising from endocrine and neuronal origin cells showing highly variable clinical behavior. By the time these tumors are discovered, up to 14% of patients with histologically proven NETs have metastasis, with the liver as the most frequently affected organ. Sometimes, no known primary site can be identified via routine imaging. Neuroendocrine tumors of unknown origin carry a poorer prognosis (compared with metastatic NETs with a known primary site) because of a lack of tailored surgical intervention and appropriate medical therapy (eg, chemotherapy or targeted therapy). A multimethod approach is frequently used in the trial to accurately determine the primary site for NETs of unknown primary sites and may include clinical, laboratory, radiological, histopathological, and surgical data. New molecular techniques using the genomic approach to identify the molecular signature have shown promising results. Various imaging modalities include ultrasound, computed tomography (CT), dual-energy CT, magnetic resonance imaging, and functional and hybrid imaging (positron emission tomography/CT, positron emission tomography/magnetic resonance imaging); somatostatin receptor imaging with new tracers is frequently used in an attempt for localization of the primary site.
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Affiliation(s)
- Taher Daoud
- From the Division of Diagnostic Imaging, Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center
| | - Ajaykumar C Morani
- From the Division of Diagnostic Imaging, Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center
| | - Rebecca Waters
- Department of Pathology and Lab Medicine MD Anderson Cancer Center, Houston, TX
| | - Priya Bhosale
- From the Division of Diagnostic Imaging, Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center
| | - Mayur K Virarkar
- Department of Radiology, University of Florida College of Medicine, Jacksonville, FL
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Hoogenkamp DS, de Wit-van der Veen LJ, Huizing DMV, Tesselaar MET, van Leeuwaarde RS, Stokkel MPM, Lam MGEH, Braat AJAT. Advances in Radionuclide Therapies for Patients with Neuro-endocrine Tumors. Curr Oncol Rep 2024; 26:551-561. [PMID: 38598035 PMCID: PMC11062977 DOI: 10.1007/s11912-024-01521-w] [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] [Accepted: 03/21/2024] [Indexed: 04/11/2024]
Abstract
PURPOSE OF REVIEW To provide insights into the role of peptide receptor radionuclide therapy (PRRT) in patients with advanced neuroendocrine tumors (NET) and an overview of possible strategies to combine PRRT with locoregional and systemic anticancer treatments. RECENT FINDINGS Research on combining PRRT with other treatments encompasses a wide variety or treatments, both local (transarterial radioembolization) and systemic therapies, chemotherapy (i.e., capecitabine and temozolomide), targeted therapies (i.e., olaparib, everolimus, and sunitinib), and immunotherapies (e.g., nivolumab and pembrolizumab). Furthermore, PRRT shows promising first results as a treatment prior to surgery. There is great demand to enhance the efficacy of PRRT through combination with other anticancer treatments. While research in this area is currently limited, the field is rapidly evolving with numerous ongoing clinical trials aiming to address this need and explore novel therapeutic combinations.
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Affiliation(s)
- Denise S Hoogenkamp
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
| | - Linda J de Wit-van der Veen
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
| | - Daphne M V Huizing
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
| | - Margot E T Tesselaar
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Rachel S van Leeuwaarde
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
- Department of Endocrinology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marcel P M Stokkel
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
| | - Marnix G E H Lam
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
| | - Arthur J A T Braat
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
- ENETS Center of Excellence NKI-AVL, The Netherlands Cancer Institute/UMC Utrecht, Amsterdam, The Netherlands.
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
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Hofland J, Refardt JC, Feelders RA, Christ E, de Herder WW. Approach to the Patient: Insulinoma. J Clin Endocrinol Metab 2024; 109:1109-1118. [PMID: 37925662 PMCID: PMC10940262 DOI: 10.1210/clinem/dgad641] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/02/2023] [Accepted: 10/27/2023] [Indexed: 11/07/2023]
Abstract
Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.
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Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
| | - Julie C Refardt
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
- ENETS Center of Excellence, Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland
| | - Richard A Feelders
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
| | - Emanuel Christ
- ENETS Center of Excellence, Division of Endocrinology, Diabetology and Metabolism, University Hospital Basel, CH-4031 Basel, Switzerland
| | - Wouter W de Herder
- ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus MC and Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands
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10
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Yit LFN, Li Y. A Review of the Evolving Role of Radiotherapy in the Treatment of Neuroendocrine Neoplasms. Neuroendocrinology 2024; 114:856-865. [PMID: 38432216 DOI: 10.1159/000538140] [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: 11/27/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are rare tumours that develop from neuroendocrine cells in various parts of the body. The management of this disease poses a significant challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. A multidisciplinary approach is often required in complex clinical situations. Radiotherapy (RT) plays a key role in managing NETs in both curative and palliative settings. SUMMARY In this review, we summarize and discuss recent developments in the field of advanced RT in early-stage, locally advanced, and metastatic NENs. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NENs.
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Affiliation(s)
- Ling Fung Nelson Yit
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Youquan Li
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
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11
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Sultana Q, Kar J, Verma A, Sanghvi S, Kaka N, Patel N, Sethi Y, Chopra H, Kamal MA, Greig NH. A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management. J Clin Med 2023; 12:5138. [PMID: 37568540 PMCID: PMC10420169 DOI: 10.3390/jcm12155138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.
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Affiliation(s)
- Qamar Sultana
- Department of Medicine, Deccan College of Medical Sciences, Hyderabad 500058, India;
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
| | - Jill Kar
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
| | - Amogh Verma
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Shreya Sanghvi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai 400022, India
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India;
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China;
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1216, Bangladesh
- Enzymoics, Hebersham, NSW 2770, Australia
- Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia
| | - Nigel H. Greig
- Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
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12
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Stiefel R, Lehmann K, Winder T, Siebenhüner AR. What have we learnt from the past - would treatment decisions for GEP-NET patients differ between 2012 to 2016 by the new recommendations in 2022? BMC Cancer 2023; 23:148. [PMID: 36782152 PMCID: PMC9926660 DOI: 10.1186/s12885-023-10567-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/19/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. METHODS Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. RESULTS Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001). CONCLUSION This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.
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Affiliation(s)
- Rahel Stiefel
- grid.414526.00000 0004 0518 665XMedical Oncology and Hematology, Triemli Hospital Zurich, Zurich, Switzerland
| | - Kuno Lehmann
- grid.7400.30000 0004 1937 0650Department of Surgery and Transplantation, University Hospital and University of Zurich, Zurich, Switzerland
| | - Thomas Winder
- grid.413250.10000 0000 9585 4754Internal Medicine II, Hematology, Oncology and Gastroenterology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria ,grid.7400.30000 0004 1937 0650University of Zurich, Zurich, Switzerland
| | - Alexander R. Siebenhüner
- grid.7400.30000 0004 1937 0650Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland ,Clinic of Internal Medicine and Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland
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Brighi N, Lamberti G, Andrini E, Mosconi C, Manuzzi L, Donati G, Lisotti A, Campana D. Prospective Evaluation of MGMT-Promoter Methylation Status and Correlations with Outcomes to Temozolomide-Based Chemotherapy in Well-Differentiated Neuroendocrine Tumors. Curr Oncol 2023; 30:1381-1394. [PMID: 36826067 PMCID: PMC9955977 DOI: 10.3390/curroncol30020106] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 01/13/2023] [Accepted: 01/16/2023] [Indexed: 01/19/2023] Open
Abstract
Temozolomide (TEM) as a single agent or in combination with capecitabine (CAPTEM) is active in well-differentiated advanced neuroendocrine tumors (NETs) of gastro-entero-pancreatic and thoracic origin. The predictive role of MGMT-promoter methylation in this setting is controversial. We sought to prospectively evaluate the MGMT-promoter methylation status ability to predict outcomes to TEM-based chemotherapy in patients with NET. A single-center, prospective, observational study has been conducted at the ENETS Center-of-Excellence Outpatient Clinic of the IRCCS Policlinico Sant'Orsola-Malpighi in Bologna, Italy. Patients with advanced, gastro-entero-pancreatic or lung well-differentiated NETs candidate to TEM-based chemotherapy and with available tumor samples for MGMT-promoter methylation assessment were included. The MGMT-promoter methylation status was analyzed by using pyrosequencing. The primary endpoint was progression-free survival (PFS) by the MGMT-promoter methylation status. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival outcomes were compared by restricted mean survival time (RMST) difference. Of 26 screened patients, 22 were finally enrolled in the study. The most frequent NET primary sites were the pancreas (64%) and the lung (23%). MGMT promoter was methylated in five tumors (23%). At a median follow-up time of 47.2 months (95%CI 29.3-89.7), the median PFS was 32.8 months (95%CI 17.2-NA), while the median OS was not reached. Patients in the methylated MGMT group, when compared to those in the unmethylated MGMT group, had longer PFS (median not reached [95%CI NA-NA] vs. 30.2 months [95%CI 15.2-NA], respectively; RMST p = 0.005) and OS (median not reached [95%CI NA-NA] vs. not reached [40.1-NA], respectively; RMST p = 0.019). After adjusting for confounding factors, the MGMT-promoter methylation status was independently associated to the PFS. Numerically higher ORR (60% vs. 24%; p = 0.274) and DCR (100% vs. 88%; p = 1.00) were observed in the methylated vs. unmethylated MGMT group. TEM-based chemotherapy was well-tolerated (adverse events grade ≥3 < 10%). In this prospective study, MGMT-promoter methylation predicted better outcomes to TEM-based chemotherapy in patients with NET.
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Affiliation(s)
- Nicole Brighi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Giuseppe Lamberti
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Elisa Andrini
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Lisa Manuzzi
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy
| | - Giada Donati
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, 40026 Bologna, Italy
| | - Davide Campana
- Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi University Hospital, ENETS Center of Excellence, 40138 Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via P. Albertoni 15, 40138 Bologna, Italy
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Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review. J Clin Med 2023; 12:jcm12020717. [PMID: 36675645 PMCID: PMC9861419 DOI: 10.3390/jcm12020717] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/08/2023] [Accepted: 01/13/2023] [Indexed: 01/19/2023] Open
Abstract
Neuroendocrine tumors (NETs) are rare neoplasms with a wide spectrum of clinical behavior, from the long survival of well-differentiated NETs to the dismal prognosis of high-grade neuroendocrine carcinomas (NECs), being G3 NETs a recently recognized intermediate entity. While the role of chemotherapy is well established in NECs, data on NETs mostly derives from small studies, experts' opinions, and extrapolating results from small-cell lung cancer studies. This narrative review aims to summarize available evidence about the use of chemotherapy in the setting of G1-2 NETs and G3 NETs. We performed literature research in PubMed Library for all articles published up to September 2022 about the efficacy of chemotherapy in NETs. Treatment regimens with STZ-5FU, CAPTEM, and anti-metabolite-based treatment are the most active and tolerated in gastroenteropancreatic NETs (GEP-NETs) G1-G2, while platinum-based regimens (FOLFOX/XELOX) and TEM/CAPTEM showed the best activity in thoracic NETs. Solid evidence about chemotherapy efficacy in G3 NETs is still lacking. Literature data support the use of chemotherapy in low-intermediate grade NETs after the failure of other therapies or if tumor shrinkage is needed. Studies assessing G3 NETs independently from NECs are needed to better understand the role of chemotherapy in this setting.
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Zhang Q, Qiu YJ, Yang DH, Lu XY, Chen S, Dong Y, Wang WP. Differential diagnosis between pancreatic solid pseudopapillary tumors and pancreatic neuroendocrine tumors based on contrast enhanced ultrasound imaging features. Clin Hemorheol Microcirc 2023; 85:421-431. [PMID: 37718786 DOI: 10.3233/ch-231932] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
Abstract
PURPOSES To evaluate the application of contrast enhanced ultrasound (CEUS) in preoperatively differential diagnosis between pancreatic solid pseudopapillary tumors (SPTs) and pancreatic neuroendocrine tumors (pNETs). PATIENTS AND METHODS This retrospective study was approved by Institutional Review Board. Patients with surgical resection and histopathological diagnosis as SPTs and pNETs were included. All patients underwent B mode ultrasound (BMUS) and CEUS examinations within one week before surgical operation. On BMUS, the size, location, echogenicity, calcification, and margin of lesions were observed and recorded. On CEUS imaging, enhancement patterns, and enhancement degrees were recorded and analyzed. An independent t-test or Mann-Whitney U test was used for comparison between continuous variables. Chi-square test was used to compare the CEUS patterns. RESULTS From February 2017 to Dec 2022, patients diagnosed as SPTs (n = 39) and pNETs (n = 48) were retrospectively included. On BMUS, anechoic cystic changes (19/39, 48.72%) and hyperechoic calcification (14/39, 35.90%) are more commonly detected in SPTs (P = 0.000). On CEUS imaging, the majority of SPTs (27/39, 69.23%) showed hypo-enhancement in the arterial phase, while most of the pNETs (36/48, 75.00%) showed hyper- or iso-enhancement in the arterial phase (P = 0.000). In the venous phase, most of the SPTs (32/39, 82.05%) showed hypo-enhancement, while over half of pNETs (29/48, 60.42%) showed hyper- or iso-enhancement compared to pancreatic parenchyma (P = 0.001). CONCLUSIONS CEUS is a valuable and non-invasive imaging method to make preoperatively differential diagnoses between SPTs and pNETs.
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Affiliation(s)
- Qi Zhang
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Jie Qiu
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dao-Hui Yang
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen, China
| | - Xiu-Yun Lu
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sheng Chen
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
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Gonzáles-Yovera JG, Roseboom PJ, Concepción-Zavaleta M, Gutiérrez-Córdova I, Plasencia-Dueñas E, Quispe-Flores M, Ramos-Yataco A, Alcalde-Loyola C, Massucco-Revoredo F, Paz-Ibarra J, Concepción-Urteaga L. Diagnosis and management of small bowel neuroendocrine tumors: A state-of-the-art. World J Methodol 2022; 12:381-391. [PMID: 36186753 PMCID: PMC9516545 DOI: 10.5662/wjm.v12.i5.381] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/22/2022] [Accepted: 08/05/2022] [Indexed: 02/08/2023] Open
Abstract
This review provides an update on the epidemiology, pathophysiology, symptoms, diagnosis and treatment of neuroendocrine neoplasms (NENs) of the small bowel (SB). These NENs are defined as a group of neoplasms deriving from neuroendocrine cells. NENs are currently the most common primary tumors of the SB, mainly involving the ileum, making the SB the most frequently affected part of the gastrointestinal tract. SB NENs by definition are located between the ligament of Treitz and the ileocecal valve. They are characterized by small size and induce an extensive fibrotic reaction in the small intestine including the mesentery, resulting in narrowing or twisting of the intestine. Clinical manifestations of bowel functionality are related to the precise location of the primary tumor. The majority of them are non-functional NENs and generally asymptomatic; in an advanced stage, NENs present symptoms of mass effect by non-specific abdominal pain or carcinoid syndrome which appears in patients with liver metastasis (around 10%). The main manifestations of the carcinoid syndrome are facial flushing (94%), diarrhea (78%), abdominal cramps (50%), heart valve disease (50%), telangiectasia (25%), wheezing (15%) and edema (19%). Diagnosis is made by imaging or biochemical tests, and the order of request will depend on the initial diagnostic hypothesis, while confirmation will always be histological. All patients with a localized SB NEN with or without near metastasis in the mesentery are recommended for curative resection. Locoregional and distant spread may be susceptible to several therapeutic strategies, such as chemotherapy, somatostatin analogs and palliative resection.
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Affiliation(s)
| | - Pela J Roseboom
- Division of Emergency Medicine, Regional Academic Hospital of Trujillo, Trujillo 13011, Peru
| | | | | | | | - María Quispe-Flores
- Division of Endocrinology, Guillermo Almenara Irigoyen National Hospital, Lima 12590, Peru
| | - Anthony Ramos-Yataco
- Division of Internal Medicine, Ricardo Cruzado Rivarola Hospital, Ica 110301, Peru
| | | | | | - José Paz-Ibarra
- Department of Medicine, School of Medicine, National University of San Marcos, Lima 15001, Peru
| | - Luis Concepción-Urteaga
- Division of Internal Medicine, School of Medicine, National University of Trujillo, Trujillo 13011, Peru
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Modica R, Liccardi A, Minotta R, Cannavale G, Benevento E, Colao A. Therapeutic strategies for patients with neuroendocrine neoplasms: current perspectives. Expert Rev Endocrinol Metab 2022; 17:389-403. [PMID: 35822906 DOI: 10.1080/17446651.2022.2099840] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/06/2022] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies mainly arising in the gastroenteropancreatic (GEP) and bronchopulmonary systems, with steadily increasing incidence. The therapeutic landscape has widened and the therapeutic strategy should be based on new sequences and combinations, still debated. AREAS COVERED Herein, we provide an overview of current approved pharmacological treatments in patients with NENs, with the aim to summarize evidence of efficacy of the main different options in GEP and pulmonary NENs, principally focusing on somatostatin analogs (SSAs), targeted therapy with everolimus and sunitinib, peptide receptor radionuclide therapy (PRRT) and chemotherapy. We discuss biological rationale and toxicities, including current indications according to differentiation and placement in the therapeutic algorithm, clinical trials, and combinations. Furthermore, we recommend areas for further research. EXPERT OPINION Therapeutic management of patients with NENs represents a challenge for clinicians and the identification of effective sequences and combinations is of utmost importance. Major efforts should be directed to early identify and overcome resistance and to limit toxicity. The progress in the therapeutic management of NENs grows faster and the choice of the best approach should be based on randomized clinical trials, as well as on long-term, real-world data.
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Affiliation(s)
- Roberta Modica
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Alessia Liccardi
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Roberto Minotta
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Giuseppe Cannavale
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Elio Benevento
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - Annamaria Colao
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
- UNESCO Chair, Education for Health and Sustainable Development, Federico II University, Naples, Italy
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Hope TA, Pavel M, Bergsland EK. Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy: When Is the Right Time? J Clin Oncol 2022; 40:2818-2829. [PMID: 35649195 PMCID: PMC9390818 DOI: 10.1200/jco.22.00176] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/14/2022] [Accepted: 04/18/2022] [Indexed: 12/29/2022] Open
Abstract
Since its approval in 2018 by the US Food and Drug Administration, peptide receptor radionuclide therapy (PRRT) has become a mainstay in the treatment of neuroendocrine tumors. Lutetium-177-DOTATATE, the only approved agent, is indicated for the treatment of gastroenteropancreatic-neuroendocrine tumors. Although patient selection appears straightforward with somatostatin receptor-positron emission tomography, there is considerable complexity when deciding which patients to treat and when to start PRRT. Herein, we review the many factors that affect patient selection, focusing on the optimal patients to treat. Although significant effort has been expended to determine which patients benefit the most from PRRT, a validated predictive biomarker remains elusive. Although PRRT has been used for more than 2 decades in Europe and standards of care exist for safe treatment, there remain numerous questions regarding when PRRT should be used relative to other treatments. It is important to remember that multidisciplinary discussions are essential. Currently, there are a number of ongoing studies looking to assess the efficacy of PRRT compared with other treatment options and to optimize treatment through combination therapy, different dosing strategies, or use of different radionuclides and radioligands.
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Affiliation(s)
- Thomas A. Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
- Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, San Francisco, CA
- Department of Radiology, San Francisco VA Medical Center, San Francisco, CA
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Emily K. Bergsland
- Helen Diller Family Comprehensive Cancer Centre, University of California, San Francisco, San Francisco, CA
- Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA
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Karlafti E, Charalampidou M, Fotiadou G, Abba Deka I, Raptou G, Kyriakidis F, Panidis S, Ioannidis A, Protopapas AA, Netta S, Paramythiotis D. Ampullary Large-Cell Neuroendocrine Carcinoma, a Diagnostic Challenge of a Rare Aggressive Neoplasm: A Case Report and Literature Review. Diagnostics (Basel) 2022; 12:1797. [PMID: 35892508 PMCID: PMC9332052 DOI: 10.3390/diagnostics12081797] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/15/2022] [Accepted: 07/19/2022] [Indexed: 11/17/2022] Open
Abstract
Ampullary large-cell neuroendocrine carcinomas (LCNECs) are extremely rare, and available data are limited on case reports. They present with jaundice, non-specific abdominal pain, or weight loss, imitating adenocarcinoma. Their incidence increases due to the improved diagnostic techniques. However, preoperative diagnosis remains challenging. We report the case of a 70-year-old man with a history of metabolic syndrome, cholecystectomy, and right hemicolectomy, presenting with jaundice. Laboratory results showed increased liver biochemistry indicators and elevated CA 19-9. Esophagogastroduodenoscopy revealed an ulcerative tumor on the ampulla of Vater, and the biopsy revealed neuroendocrine carcinoma. Although computed tomography (CT) detected enlarged regional lymph nodes, the positron emission tomography (PET) showed a hyperactive lesion only in this area. Pylorus-preserving pancreatoduodenectomy with R0 resection was performed. Pathologic evaluation of the 3.1 × 1.9 cm tumor revealed an LCNEC with immunohistochemical positivity at Synaptophysin, EMA, CD56, and cytokeratin CK8/18. The Ki-67 index was 45%. Two out of the nine dissected lymph nodes were occupied by the neoplasm. The patient was discharged home free of symptoms, and adjuvant chemotherapy with carboplatin + etoposide was initiated. A comprehensive review of the reported cases showed that the preoperative biopsy result was different from the final diagnosis in few cases, regarding the subtypes. Conventional radiology cannot identify small masses, and other methods, such as endoscopy, magnetic resonance cholangiopancreatography (MRCP), and FDG-PET scan, might aid the diagnosis. Diagnosis is based on histology and immunohistochemical markers of the surgical specimens. The treatment of choice is pancreatoduodenectomy, followed by adjuvant chemotherapy. However, recurrence is frequent, and the prognosis remains poor.
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Affiliation(s)
- Eleni Karlafti
- Emergency Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece;
| | - Maria Charalampidou
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
| | - Georgia Fotiadou
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
| | - Ioanna Abba Deka
- Pathology Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (I.A.D.); (G.R.)
| | - Georgia Raptou
- Pathology Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (I.A.D.); (G.R.)
| | | | - Stavros Panidis
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
| | - Aristeidis Ioannidis
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
| | - Adonis A. Protopapas
- First Propaedeutic Department of Internal Medicine, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece;
| | - Smaro Netta
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
| | - Daniel Paramythiotis
- First Propaedeutic Surgical Department, University Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 546 21 Thessaloniki, Greece; (G.F.); (S.P.); (A.I.); (S.N.); (D.P.)
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Longo-Muñoz F, Castellano D, Alexandre J, Chawla SP, Fernández C, Kahatt C, Alfaro V, Siguero M, Zeaiter A, Moreno V, Sanz-García E, Awada A, Santaballa A, Subbiah V. Lurbinectedin in patients with pretreated neuroendocrine tumours: Results from a phase II basket study. Eur J Cancer 2022; 172:340-348. [PMID: 35830841 DOI: 10.1016/j.ejca.2022.06.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 06/03/2022] [Accepted: 06/10/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy. PATIENTS AND METHODS This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m2 as a 1-h intravenous infusion every 3 weeks in 32 NETs patients treated in the second- or third-line setting. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1 assessed by the investigators. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8-21.4%). Median DoR was 4.7 months (95% CI, 4.0-5.4 months), median PFS was 1.4 months (95% CI, 1.2-3.0 months) and median OS was 7.4 months (95% CI, 3.4-16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%). CONCLUSIONS Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population. TRIAL REGISTRATION NUMBER Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42. CLINICALTRIALS gov reference: NCT02454972.
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Affiliation(s)
| | - Daniel Castellano
- Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | - Sant P Chawla
- Medical Oncology, Sarcoma Oncology Center, Santa Monica CA 90403, USA
| | | | | | | | | | - Ali Zeaiter
- Clinical R&D, PharmaMar, Colmenar Viejo, Spain
| | - Victor Moreno
- Medical Oncology, START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain
| | - Enrique Sanz-García
- Medical Oncology, Vall d'Hebron Hospital Campus and Institute of Oncology (VHIO), Barcelona, Spain
| | - Ahmad Awada
- Medical Oncology, Institut Jules Bordet, Université Libre De Bruxelles, Brussels, Belgium
| | | | - Vivek Subbiah
- Medical Oncology, UT MD Anderson Cancer Center, Houston, USA.
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Survival effects of primary and metastatic surgical treatment in metastatic small intestinal tumors: A propensity score–matching study. PLoS One 2022; 17:e0270608. [PMID: 35749551 PMCID: PMC9231803 DOI: 10.1371/journal.pone.0270608] [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: 02/16/2022] [Accepted: 06/13/2022] [Indexed: 11/25/2022] Open
Abstract
Objective To analyze the effects of primary tumor resection and metastatic lesion resection on the survival of metastatic small intestinal tumors. Methods The research subjects were patients with metastatic small bowel tumors identified from 2004 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and Kaplan–Meier analyses were performed to analyze the effect of surgery on the prognosis. Results A total of 4,034 patients from the SEER database were analyzed. Both before and after the propensity score–matching analysis, the prognosis of patients who underwent primary tumor surgery and metastatic surgery was better than that of patients who did not undergo surgery; all were patients with metastatic small bowel adenocarcinoma (mSIA) or metastatic small intestinal neuroendocrine tumors (mSI-NETs) (all p < .005). Patients with mSIA and adequate lymph node dissection had a longer prognosis than mSIA patients with inadequate lymph node dissection, but this survival benefit was not present in mSI-NET patients. It made no difference in the prognosis of mSIA and mSI-NETs whether localized surgery or intestine-ectomy was performed. Patients with mSIA who underwent primary and metastatic excision plus chemotherapy had the best overall survival and cancer-specific survival rates, whereas mSI-NET patients who underwent primary and metastatic excision had the best overall survival and cancer-specific survival rates (all p < .001). Conclusion In these carefully selected patients, primary tumor resection and/or metastatic lesion resection significantly improved the survival rates for patients with mSIA and mSI-NETs. The mSIA patients with resectable primary tumors seemed to require a sufficient number of lymph node dissections more than the patients with well-differentiated mSI-NETs.
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22
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Gao H, Dong J, Zhang W, Xu H, Ye L, Li H, Wang W, Liu L, Yu X. The optimal duration of capecitabine plus temozolomide in patients with well-differentiated pancreatic NETs with or without maintenance therapy. J Neuroendocrinol 2022; 34:e13112. [PMID: 35380016 DOI: 10.1111/jne.13112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 02/18/2022] [Accepted: 02/25/2022] [Indexed: 12/01/2022]
Abstract
BACKGROUND The optimal duration of capecitabine combined with temozolomide (CapTem) for metastatic pancreatic neuroendocrine tumours (PanNETs) remains controversial. The present study aimed to assess the activity and safety of prolonged CapTem and Cap maintenance therapy in patients with metastatic PanNETs. METHODS Retrospective real-world data of 94 patients with metastatic PanNETs were obtained from one cancer centre. Fifteen patients were treated with Cap maintenance therapy after fixed 12-13 cycles of CapTem (group I), 44 patients were treated with prolonged CapTem until disease progression (group II), and 35 patients were treated with fixed 12-13 cycles of CapTem (group III). RESULTS The mean ± SE follow-up period was 41.79 ± 26.31 months. The median CapTem treatment duration was 12 months in group I and 14 months in group II. The median time to best partial response was 12 months both in groups I and group II. The objective response rates of groups I and II were significantly higher than those of group III (73.3%, 41.9%, and 20%, respectively, p = .002). The median progression-free survival (mPFS) of group I and group II was significantly higher than that of group III (35 months, 26 months vs. 19 months, p < .001). Safety analysis of the three groups indicated rare events of grade 3-4 toxicities, with nausea, vomiting, fatigue, and anaemia being the most common adverse effects. CONCLUSIONS Patients with PanNETs who responded well to CapTem treatment may benefit from prolonged CapTem and Cap maintenance therapy after fixed cycles. Prospective studies are encouraged to further explore the prolonged CapTem treatment and maintenance therapy.
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Affiliation(s)
- Heli Gao
- 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
| | - Jia Dong
- 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
| | - Wuhu Zhang
- 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
| | - Huaxiang 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
| | - Longyun 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
| | - Hao Li
- 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
| | - Wenquan 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
| | - Liang Liu
- 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
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Shi H, Chen H, Qian B, Huang Z, Tan P, Peng Y, Tang X, Ye M. The 100 most cited articles on pancreatic neuroendocrine tumors from 2000 to 2020: a bibliometric analysis. Jpn J Clin Oncol 2022; 52:251-259. [PMID: 34954797 DOI: 10.1093/jjco/hyab205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 12/04/2021] [Indexed: 02/05/2023] Open
Abstract
PURPOSE The present study attempted to identify 100 most cited articles on pancreatic neuroendocrine tumors and characterize them via bibliometric analysis whereby it would provide an insight into the progress and trend in this field. METHODS Records regarding pancreatic neuroendocrine tumors and published between 2000 and 2020 were retrieved in 2021 through the Web of Science to identify the 100 most cited articles. RESULTS The 100 articles were screened in 17 434 records. The number of citations of the top-cited articles ranged from 151 to 1867. These articles were published in 47 journals among which the Journal of Clinical Oncology produced the most articles (n = 10). The USA contributed most of the articles (n = 44). Articles enrolled came from 58 institutions; the University of California System of the USA came to the top (n = 7). More than half of the articles were clinical studies (n = 55), basic science research reports accounting for a quarter. In clinical topics (n = 73), treatment issues were the most concerned (n = 21), in which more articles focused on targeted inhibitors. Articles about gene mutation were cited most frequently in basic science topics (n = 27). CONCLUSIONS This bibliometric analysis reflected the brief the progress and highlighted current trend in pancreatic neuroendocrine tumor research, providing references for further study.
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Affiliation(s)
- Hao Shi
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hao Chen
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Baolin Qian
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Zhiwei Huang
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Peng Tan
- Sichuan Provincial Academician (Expert) Workstation, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yan Peng
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Mingxin Ye
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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Gao H, Dong J, Zhang W, Xu H, Ye L, Li H, Ni Q, Wang W, Liu L. Sequential Capecitabine/Temozolomide and Sunitinib Treatment in Patients With Metastatic Well-Differentiated Grade 1/Grade 2 Pancreatic Neuroendocrine Tumors. Endocr Pract 2022; 28:292-297. [PMID: 34454077 DOI: 10.1016/j.eprac.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 08/17/2021] [Accepted: 08/18/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic pancreatic neuroendocrine tumors (PanNETs) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced grade 1/grade 2 PanNETs. METHODS In total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group 1), and 19 patients were treated with CAPTEM followed by sunitinib (group 2). RESULTS Twenty-three patients were treated with first-line sunitinib or CAPTEM, and 20 patients were pretreated with somatostatin analog (SSA) or SSA in combination with transcatheter arterial chemoembolization. The objective response rate with first-line treatment was similar in both groups, whereas that with second-line treatment was higher in group 1 than in group 2, albeit with no significant differences (21.1% vs 5.3%, respectively; P = .205). Median progression-free survival (mPFS) for first-line and second-line treatments did not differ between the 2 groups (11 and 12 months vs 12 and 8 months, respectively). Following subgroup analyses, treatment with first-line sunitinib and sunitinib after pretreated SSA had a longer mPFS than that with second-line sunitinib after CAPTEM (11 months vs 8 months, respectively; P = .046), whereas treatment with first-line CAPTEM and CAPTEM after pretreated SSA had an mPFS similar to that of second-line CAPTEM after sunitinib treatment. CAPTEM and sunitinib had similar tolerability. CONCLUSION Alternating sunitinib and CAPTEM were well tolerated and associated with similar mPFS in grade 1/grade 2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.
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Affiliation(s)
- Heli Gao
- 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
| | - Jia Dong
- 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
| | - Wuhu Zhang
- 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
| | - Huaxiang 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
| | - Longyun 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
| | - Hao Li
- 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
| | - Quanxing Ni
- 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
| | - Wenquan 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.
| | - Liang Liu
- 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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Lee L, Ramos-Alvarez I, Jensen RT. Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies. Cancers (Basel) 2022; 14:1250. [PMID: 35267558 PMCID: PMC8909561 DOI: 10.3390/cancers14051250] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
- National Kyushu Cancer Center, Department of Hepato-Biliary-Pancreatology, Fukuoka 811-1395, Japan
| | - Irene Ramos-Alvarez
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [DOI: - merola e, michielan a, rozzanigo u, et al.therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: state-of-the-art and future perspectives.world j gastrointestinal surgery, volume 14 number 2 february 27, 2022, doi: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
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27
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [PMID: 35317548 PMCID: PMC8908345 DOI: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 10/18/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Andrea Michielan
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Umberto Rozzanigo
- Department of Radiology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Marco Erini
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Sandro Sferrazza
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Stefano Marcucci
- Department of Surgery, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Sartori
- Department of Pathology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Giovanni de Pretis
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Franca Chierichetti
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
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Pusceddu S, Prinzi N, Tafuto S, Ibrahim T, Filice A, Brizzi MP, Panzuto F, Baldari S, Grana CM, Campana D, Davì MV, Giuffrida D, Zatelli MC, Partelli S, Razzore P, Marconcini R, Massironi S, Gelsomino F, Faggiano A, Giannetta E, Bajetta E, Grimaldi F, Cives M, Cirillo F, Perfetti V, Corti F, Ricci C, Giacomelli L, Porcu L, Di Maio M, Seregni E, Maccauro M, Lastoria S, Bongiovanni A, Versari A, Persano I, Rinzivillo M, Pignata SA, Rocca PA, Lamberti G, Cingarlini S, Puliafito I, Ambrosio MR, Zanata I, Bracigliano A, Severi S, Spada F, Andreasi V, Modica R, Scalorbi F, Milione M, Sabella G, Coppa J, Casadei R, Di Bartolomeo M, Falconi M, de Braud F. Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors. JAMA Netw Open 2022; 5:e220290. [PMID: 35201309 PMCID: PMC8874344 DOI: 10.1001/jamanetworkopen.2022.0290] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/03/2021] [Indexed: 02/05/2023] Open
Abstract
IMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVE To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95% CI, 0.4-1.0 years]; HR, 0.37 [95% CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95% CI, 10.7-14.1 years] vs 11.6 years [95% CI, 9.1-13.4 years]; HR, 0.81 [95% CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95% CI, 9.2-17.9 years]; HR, 0.83 [95% CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95% CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95% CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95% CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95% CI, 0.12-0.34]; grade 2: aHR, 0.52 [95% CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95% CI, 0.24-0.61]; intestinal: aHR, 0.19 [95% CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95% CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95% CI, 0.29-1.43; P = .31). CONCLUSIONS AND RELEVANCE In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.
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Affiliation(s)
- Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Milan, Italy
| | - Natalie Prinzi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Milan, Italy
| | - Salvatore Tafuto
- Oncologia Clinica e Sperimentale Sarcomi e Tumori Rari, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, Naples, Italy
| | - Toni Ibrahim
- Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” Meldola, Italy
| | - Angelina Filice
- Nuclear Medicine Unit, Azienda Unità Sanitaria Locale–IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Maria Pia Brizzi
- Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Sergio Baldari
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Nuclear Medicine Unit, University of Messina, Messina, Italy
| | - Chiara M. Grana
- Division of Nuclear Medicine, IRCCS Istituto Europeo di Oncologia, Milan, Italy
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliera–Universitaria Bologna, Neuroendocrine Tumor Team Bologna, ENETS Center of Excellence Bologna, Bologna, Italy
| | - Maria Vittoria Davì
- Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, ENETS Center of Excellence, Verona, Italy
| | - Dario Giuffrida
- Oncologia Medica, Istituto Oncologico del Mediterraneo, Viagrande (Catania), Italy
| | - Maria Chiara Zatelli
- Department of Medical Sciences, Section of Endocrinology, Geriatrics and Internal Medicine, University of Ferrara, Ferrara, Italy
| | - Stefano Partelli
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Hospital IRCCS, Università Vita-Salute San Raffaele, ENETS Center of Excellence, Milano, Italy
| | - Paola Razzore
- Department of Internal Medicine, Division of Endocrinology, A.O. Ordine Mauriziano, Turin, Italy
| | - Riccardo Marconcini
- Department of Oncology, Santa Chiara Hospital, Azienda Ospedaliero–Universitaria Pisana, Pisa, Italy
| | - Sara Massironi
- Division of Gastroenterology, Ospedale San Gerardo, University of Milano–Bicocca, Monza, Italy
| | - Fabio Gelsomino
- Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy
| | - Antongiulio Faggiano
- Department of Clinical and Molecular Medicine, Endocrinology Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Elisa Giannetta
- Department of Experimental Medicine, Sapienza Università Roma, Rome, Italy
| | - Emilio Bajetta
- Istituto di Oncologia, Policlinico di Monza, Monza, Italy
| | - Franco Grimaldi
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia, Udine, Italy
| | - Mauro Cives
- Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy
- National Cancer Center, Tumori Institute Giovanni Paolo II, Bari, Italy
| | - Fernando Cirillo
- Department of Surgery, General Surgery Unit, Gruppo Tumori Rari, Azienda Socio-Sanitaria Territoriale–Cremona, Cremona, Italy
| | | | - Francesca Corti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Milan, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero–Universitaria Di Bologna, Bologna, Italy
- Department of Internal Medicine and Surgery, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | | | - Luca Porcu
- Methodology for Clinical Research Laboratory, Oncology Department, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - Massimo Di Maio
- Department of Oncology, University of Turin, A.O. Ordine Mauriziano, Torino, Italy
| | - Ettore Seregni
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy
| | - Marco Maccauro
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy
| | - Secondo Lastoria
- Nuclear Medicine Unit, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, Naples, Italy
| | - Alberto Bongiovanni
- Osteoncology and Rare Tumors Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” Meldola, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Azienda Unità Sanitaria Locale–IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Irene Persano
- Azienda Ospedaliera Universitaria San Luigi Gonzaga, Orbassano, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Salvatore Antonio Pignata
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Nuclear Medicine Unit, University of Messina, Messina, Italy
- Nuclear Medicine Unit, Azienda Ospedaliera Papardo, Messina, Italy
| | - Paola Anna Rocca
- Division of Nuclear Medicine, IRCCS Istituto Europeo di Oncologia, Milan, Italy
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Division of Medical Oncology, IRCCS Azienda Ospedaliera–Universitaria Bologna, Neuroendocrine Tumor Team Bologna, ENETS Center of Excellence Bologna, Bologna, Italy
| | - Sara Cingarlini
- Department of Medicine, Oncology, University and Hospital Trust of Verona, ENETS Center of Excellence, Verona, Italy
| | - Ivana Puliafito
- Oncologia Medica, Istituto Oncologico del Mediterraneo, Viagrande (Catania), Italy
| | - Maria Rosaria Ambrosio
- Department of Medical Sciences, Section of Endocrinology, Geriatrics and Internal Medicine, University of Ferrara, Ferrara, Italy
| | - Isabella Zanata
- Department of Medical Sciences, Section of Endocrinology, Geriatrics and Internal Medicine, University of Ferrara, Ferrara, Italy
| | - Alessandra Bracigliano
- Oncologia Clinica e Sperimentale Sarcomi e Tumori Rari, Istituto Nazionale Tumori IRCCS, Fondazione G. Pascale, Naples, Italy
| | - Stefano Severi
- Nuclear Medicine Therapy Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” Meldola, Italy
| | - Francesca Spada
- Division of Medical Oncology, IRCCS Istituto Europeo di Oncologia, Milan, Italy
| | - Valentina Andreasi
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Hospital IRCCS, Università Vita-Salute San Raffaele, ENETS Center of Excellence, Milano, Italy
| | - Roberta Modica
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Federica Scalorbi
- Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy
| | - Massimo Milione
- First Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - Giovanna Sabella
- First Division of Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy
| | - Jorgelina Coppa
- Gastro-entero-pancreatic Surgical and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, ENETS Center of Excellence, Milan, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero–Universitaria Di Bologna, Bologna, Italy
- Department of Internal Medicine and Surgery, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Maria Di Bartolomeo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Hospital IRCCS, Università Vita-Salute San Raffaele, ENETS Center of Excellence, Milano, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università deli Studi di Milano, Milan, Italy
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Müller C, Kreissl MC, Klose S, Krause A, Keitel V, Venerito M. Long-term treatment with streptozocin/5-fluorouracil chemotherapy in patients with metastatic pancreatic neuroendocrine tumors: Case series. Medicine (Baltimore) 2022; 101:e28610. [PMID: 35089197 PMCID: PMC8797514 DOI: 10.1097/md.0000000000028610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 12/30/2021] [Indexed: 01/05/2023] Open
Abstract
RATIONALE Pancreatic neuroendocrine tumors (pNETs) are rare entities representing 1% to 3% of all malignant pancreatic neoplasms. Current guidelines recommend a combination of streptozocin (STZ) and 5-fluorouracil (5-FU) for patients with metastatic well-differentiated pNETs requiring systemic therapy. The highest median progression-free survival rate reported in previous studies for this combination was 23 months (95% confidence interval 14.5-31.5). However, it remains unclear for how long this regimen can be safely administered. PATIENT CONCERNS We report about 3 therapy-naïve patients with metastatic G2 (Ki67 10%-15%) pNETs treated with STZ/5-FU, that achieved sustained disease control for longer than 36 months. DIAGNOSIS Metastatic, well-differentiated G2 pNETs. INTERVENTIONS Systemic chemotherapy with STZ/5-FU was administered until the disease progressed. In 1 case showing a mixed response, selected metastases of increasing size were additionally treated with surgery and brachytherapy. OUTCOMES In our 3 patients with metastatic G2 pNETs, STZ/5-FU induced long-term disease control over 44, 42, and 95 months, respectively. No side effects that led to treatment discontinuation were observed. LESSONS In patients with metastatic G2 pNETs achieving disease control, STZ/5-FU can be safely administered.
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Affiliation(s)
- Christian Müller
- Otto-von-Guericke University Hospital, Department of Gastroenterology, Hepatology and Infectious Diseases, Leipziger Str. 44, Magdeburg, Germany
| | - Michael C. Kreissl
- Otto-von-Guericke University Hospital, Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Leipziger Str. 44, Magdeburg, Germany
| | - Silke Klose
- Otto-von-Guericke University Hospital, Department of Nephrology and Hypertension, Diabetes and Endocrinology, Leipziger Str. 44, Magdeburg, Germany
| | - Andreas Krause
- Esteve Pharmaceuticals GmbH, Department of Medicine and Science, Hohenzollerndamm 150-151, Berlin, Germany
| | - Verena Keitel
- Otto-von-Guericke University Hospital, Department of Gastroenterology, Hepatology and Infectious Diseases, Leipziger Str. 44, Magdeburg, Germany
| | - Marino Venerito
- Otto-von-Guericke University Hospital, Department of Gastroenterology, Hepatology and Infectious Diseases, Leipziger Str. 44, Magdeburg, Germany
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Girot P, Baudin E, Senellart H, Bouarioua N, Hentic O, Guimbaud R, Walter T, Ferru A, Roquin G, Cadiot G, Pracht M, Girot JB, Malka D, Ducreux M, Bennouna J, Matysiak-Budnik T, Hadoux J, Touchefeu Y. Oxaliplatin and 5-Fluorouracil in Advanced Well-Differentiated Digestive Neuroendocrine Tumors: A Multicenter National Retrospective Study from the French Group of Endocrine Tumors. Neuroendocrinology 2022; 112:537-546. [PMID: 34348346 DOI: 10.1159/000518650] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/22/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs); however, the available data are limited. Our aim was to assess the efficacy of FOLFOX (association of 5-fluorouracil with oxaliplatin) in a large series of patients with advanced digestive NETs. METHODS All patients with advanced digestive well-differentiated NETs treated with at least 3 cycles of FOLFOX between January 2004 and December 2018 in 12 centers from the French Group of Endocrine Tumors were included. Tumor response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria, progression free survival (PFS), and overall survival, as well as prognostic factors, were analyzed retrospectively. RESULTS One hundred fifty-five patients were included. Primary tumor locations were pancreas (n = 89), small intestine (n = 40), unknown with no evidence for lung primary (n = 13), stomach (n = 7), and rectum (n = 6). Median Ki-67 was 10%, and 65% of the tumors were grade 2. The partial response rate was 30% for pancreatic NETs, 12.5% for small intestine NETs, 38.5% for unknown primary NETs, 14% for gastric NETs, and 17% for rectal NETs. Significant prognostic factors for poor PFS after FOLFOX were progressive disease at the beginning of treatment (hazard ratio [HR] = 1.83, p = 0.007), hepatic involvement superior to 50% (HR = 2.67, p = 0.0001), and rectal primary tumor location (HR = 2.6, p = 0.0036). Among pancreatic NETs, insulinomas had a better median PFS (22 months) than other pancreatic NETs (9 months, p = 0.026) and showed a high rate (8/9) of serum glucose normalization. CONCLUSIONS FOLFOX shows a promising antitumor activity in advanced digestive NETs. Rapid symptomatic response is observed in metastatic insulinomas.
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Affiliation(s)
- Paul Girot
- Gastroenterology and Digestive Oncology Department, CHD Vendee, La Roche sur Yon, France
| | - Eric Baudin
- Endocrine Oncology Unit, Gustave Roussy, Villejuif, France
| | - Hélène Senellart
- Oncology Department, Institut de Cancérologie de L'Ouest, Saint Herblain, France
| | - Nadia Bouarioua
- Hepato-Gastroenterology Department, University Hospital of Saint-Etienne, Saint Priest en Jarez, France
| | - Olivia Hentic
- Gastroenterology Department, Hôpital Beaujon, AP-HP, Clichy, France
| | - Rosine Guimbaud
- Digestive Cancer Department, CHU Toulouse (IUCT-Rangueil-Larrey), Toulouse, France
| | - Thomas Walter
- Gastroenterology and Digestive Oncology Department, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Aurélie Ferru
- Department of Medical Oncology, University Hospital of Poitiers, Poitiers, France
| | - Guillaume Roquin
- Department of Hepato-Gastroenterology and Digestive Oncology, University Hospital of Angers, Angers, France
| | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
| | - Marc Pracht
- Department of Medical Oncology, Centre Eugene Marquis, Rennes, France
| | | | - David Malka
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Michel Ducreux
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Jaafar Bennouna
- Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes, France
| | - Tamara Matysiak-Budnik
- Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes, France
| | - Julien Hadoux
- Endocrine Oncology Unit, Gustave Roussy, Villejuif, France
| | - Yann Touchefeu
- Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes, France
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Optimization of the tumour response threshold in advanced gastroenteropancreatic neuroendocrine carcinomas treated with cisplatin/etoposide combined chemotherapy. Eur J Radiol 2021; 147:110119. [PMID: 34979297 DOI: 10.1016/j.ejrad.2021.110119] [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: 02/09/2021] [Revised: 12/05/2021] [Accepted: 12/21/2021] [Indexed: 11/20/2022]
Abstract
OBJECTIVES To identify early and more accurate imaging response criteria for computed tomography evaluation to define 'responders' in advanced gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) patients treated with cisplatin/etoposide combined chemotherapy. MATERIALS AND METHODS Thirty-seven patients with GEP-NEC treated with first-line cisplatin/etoposide (E/P) combined chemotherapy were enrolled in this study. Computed tomography scans of the chest, abdomen, and pelvis were performed at baseline, during the treatment course, and during follow-up. Tumour size was measured, and tumour response was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Receiver operating characteristic (ROC) analysis was carried out among the patients who progressed during follow-up. Thresholds from -55% to + 5% were tested by Kaplan-Meier analysis to define "responders" for significantly improved progression-free survival (PFS). The overall survival rate was compared between these two groups. RESULTS A reduction of 45% (vs. baseline) achieved the highest sensitivity (70%) and specificity (90%) by ROC analysis. This threshold divided patients into 15 responders and 22 nonresponders. Patients who were grouped as responders by the -45% threshold had a significantly longer PFS (11.06 months) than nonresponders (7.97 months, hazard ratio, 3.636; 95% confidence interval, 1.293-10.164). No significant difference was shown in overall survival between these two groups (29.1 vs. 21.4 months, P = 0.190). CONCLUSION A 45% reduction in target lesions may be considered to be a more reliable predictor than the RECIST 1.1 criteria in evaluating the outcome of GEP-NEC patients treated with E/P chemotherapy.
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Caplin ME. Can the peptide receptor radionuclide therapy [ 177Lu]Lu-DOTA-TATE provide a net benefit for NET patients? EJC Suppl 2021; 16:1-4. [PMID: 34912477 PMCID: PMC8591180 DOI: 10.1016/j.ejcsup.2021.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 06/28/2021] [Accepted: 06/29/2021] [Indexed: 11/16/2022] Open
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Opalińska M, Sowa-Staszczak A, Grochowska A, Olearska H, Hubalewska-Dydejczyk A. Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors. Front Oncol 2021; 11:687925. [PMID: 34868906 PMCID: PMC8633407 DOI: 10.3389/fonc.2021.687925] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 10/21/2021] [Indexed: 02/01/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes. AIM This study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs. METHODS Among the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment. RESULTS Neoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved. CONCLUSION PRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.
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Affiliation(s)
- Marta Opalińska
- Nuclear Medicine Unit, Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Kraków, Poland
| | - Anna Sowa-Staszczak
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
| | - Anna Grochowska
- Department of Radiology, University Hospital, Kraków, Poland
| | - Helena Olearska
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
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Espinosa-Olarte P, La Salvia A, Riesco-Martinez MC, Anton-Pascual B, Garcia-Carbonero R. Chemotherapy in NEN: still has a role? Rev Endocr Metab Disord 2021; 22:595-614. [PMID: 33843007 PMCID: PMC8346445 DOI: 10.1007/s11154-021-09638-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/23/2021] [Indexed: 02/07/2023]
Abstract
Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.
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Affiliation(s)
- Paula Espinosa-Olarte
- Oncology Department, Hospital Universitario, 12 de Octubre, Imas12, UCM, Madrid, Spain
| | - Anna La Salvia
- Oncology Department, Hospital Universitario, 12 de Octubre, Imas12, UCM, Madrid, Spain
| | | | - Beatriz Anton-Pascual
- Oncology Department, Hospital Universitario, 12 de Octubre, Imas12, UCM, Madrid, Spain
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Abstract
Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.
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Rao YY, Zhang HJ, Wang XJ, Li MF. Primary hepatic neuroendocrine tumor — 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings: A case report. World J Clin Cases 2021; 9:6450-6456. [PMID: 34435011 PMCID: PMC8362580 DOI: 10.12998/wjcc.v9.i22.6450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/11/2021] [Accepted: 06/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary hepatic neuroendocrine tumors (PHNETs) are rare hepatic tumors. Their diagnosis, which is based on radiological findings, is difficult.
CASE SUMMARY We present a case of PHNET in a 79-year-old man with no clinical symptoms. Computed tomography (CT) and 2-Deoxy-2-[fluorine-18] fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) were performed for further evaluation. A hypoattenuating mass with rim-like enhancement in segment 6 of the liver was detected on contrast-enhanced CT imaging. Increased uptake was also observed on 18F-FDG PET/CT. Histopathological and immunohistochemical examinations, which revealed a grade 2 neuroendocrine tumor (NET), confirmed the diagnosis.
CONCLUSION Diagnosing PHNET is challenging, and must be distinguished from other liver tumors. Metastatic NETs should be excluded.
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Affiliation(s)
- Yan-Ying Rao
- Department of Radiology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350000, Fujian Province, China
| | - He-Jun Zhang
- Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350000, Fujian Province, China
| | - Xiao-Jiang Wang
- Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350000, Fujian Province, China
| | - Min-Feng Li
- Department of Radiology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350000, Fujian Province, China
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Jungels C, Deleporte A. State of the art and future directions in the systemic treatment of neuroendocrine neoplasms. Curr Opin Oncol 2021; 33:378-385. [PMID: 33973550 DOI: 10.1097/cco.0000000000000740] [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: 11/26/2022]
Abstract
PURPOSE OF REVIEW Neuroendocrine neoplasms (NENs) are rare and heterogeneous malignancies whose natural evolution may be defined according to various prognostic factors, including localization of the primitive tumour, hormone secretory status, histological grade, tumour burden, tumour growth rate, expression of somatostatin receptors and fluorodeoxyglucose-avidity. The treatment of these tumours in an advanced setting is based on relatively little robust data. RECENT FINDINGS A recent pathological classification introduced a new category of high-grade but well differentiated neuroendocrine tumours (NET G3), with markedly different behaviour from neuroendocrine carcinomas (NECs). Yet, the optimal treatment of those tumours is still uncertain. Advances are needed in molecular subtyping of NENs to understand better their heterogeneity and inform personalized therapies. SUMMARY The current review summarizes the current knowledge, indicates some exciting future directions and outlines the most interesting ongoing clinical trials likely to impact current practice.
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Affiliation(s)
- Christiane Jungels
- Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
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Janson ET, Knigge U, Dam G, Federspiel B, Grønbaek H, Stålberg P, Langer SW, Kjaer A, Arola J, Schalin-Jäntti C, Sundin A, Welin S, Thiis-Evensen E, Sorbye H. Nordic guidelines 2021 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. ACTA ONCOLOGICA (STOCKHOLM, SWEDEN) 2021; 60:931-941. [PMID: 33999752 DOI: 10.1080/0284186x.2021.1921262] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic. AIM These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians.
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Affiliation(s)
- Eva Tiensuu Janson
- Department of Medical Sciences, Endocrine Oncology Uppsala University, Uppsala, Sweden*
| | - Ulrich Knigge
- Departments of Surgery C and Endocrinology PE, Faculty of Health Science, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark*
| | - Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark*
| | - Birgitte Federspiel
- Department of Pathology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark*
| | - Henning Grønbaek
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark*
| | - Peter Stålberg
- Department of Surgical Sciences, Endocrine Surgery, Uppsala University, Uppsala, Sweden*
| | - Seppo W. Langer
- Department of Oncology, Rigshospitalet, Copenhagen, Denmark*
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark*
| | - Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark*
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark*
| | - Johanna Arola
- Department of Pathology, HUSLAB, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland
| | - Camilla Schalin-Jäntti
- Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Anders Sundin
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden*
| | - Staffan Welin
- Department of Medical Sciences, Endocrine Oncology Uppsala University, Uppsala, Sweden*
| | - Espen Thiis-Evensen
- Department for Organ Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway*
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
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de Herder WW, Feelders RA, Hofland J. Medical treatment of neuroendocrine neoplasms. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 18:139-144. [DOI: 10.1016/j.coemr.2021.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Tarquini M, Ambrosio MR, Albertelli M, de Souza PB, Gafà R, Gagliardi I, Carnevale A, Franceschetti P, Zatelli MC. A tool to predict survival in stage IV entero-pancreatic NEN. J Endocrinol Invest 2021; 44:1185-1192. [PMID: 32892316 PMCID: PMC8124053 DOI: 10.1007/s40618-020-01404-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 08/22/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Well-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis. METHODS Age, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival. RESULTS Mean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p < 0.01) at EOF. We identified an NEP-D = 116 as the cutoff that significantly predicts survival. No gender differences were identified. CONCLUSIONS In our series, we confirmed NEP-Score applicability. In addition, we propose NEP-D as a simple, quick and cheap prognostic score that can help clinicians in decision making. NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy.
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Affiliation(s)
- M Tarquini
- Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Via Ariosto 35, 44100, Ferrara, Italy
| | - M R Ambrosio
- Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Via Ariosto 35, 44100, Ferrara, Italy
- Endocrine Unit, Azienda Ospedaliero-Universitaria di Ferrara, Via Aldo Moro 8, Cona, 44124, Ferrara, Italy
| | - M Albertelli
- Endocrinology, Department of Internal Medicine DiMI, University of Genova, Genoa, Italy
| | - P B de Souza
- Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Via Ariosto 35, 44100, Ferrara, Italy
| | - R Gafà
- Pathology Unit, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - I Gagliardi
- Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Via Ariosto 35, 44100, Ferrara, Italy
| | - A Carnevale
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
| | - P Franceschetti
- Endocrine Unit, Azienda Ospedaliero-Universitaria di Ferrara, Via Aldo Moro 8, Cona, 44124, Ferrara, Italy
| | - M C Zatelli
- Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, Via Ariosto 35, 44100, Ferrara, Italy.
- Endocrine Unit, Azienda Ospedaliero-Universitaria di Ferrara, Via Aldo Moro 8, Cona, 44124, Ferrara, Italy.
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Targeted Cancer Therapy: What's New in the Field of Neuroendocrine Neoplasms? Cancers (Basel) 2021; 13:cancers13071701. [PMID: 33916707 PMCID: PMC8038369 DOI: 10.3390/cancers13071701] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/29/2021] [Accepted: 03/31/2021] [Indexed: 12/18/2022] Open
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.
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Kan J, Tian Y, Shao Y, Xu H, Li X, Tang Q. Role of the ratio of NSE serum concentration in evaluating the therapeutic effect on metastatic neuroendocrine neoplasms of the liver. TUMORI JOURNAL 2021; 108:157-164. [PMID: 33759643 DOI: 10.1177/03008916211002272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Neuron-specific enolase (NSE) is one of the biomarkers of neuroendocrine neoplasms (NEN). Its level of evidence is significantly lower than some other biomarkers. However, the ratio of NSE serum concentration (NSE ratio) before and after the treatment cycle may be a good tool for evaluating the therapeutic effect of metastatic neuroendocrine neoplasms of the liver (MNENOL). METHODS We collected clinical cases of NEN with liver metastases, calculating the ratio of NSE in each case before and after the treatment cycle, using thin-slice computed tomography or magnetic resonance imaging as a reference to evaluate the therapeutic effect. We analyzed the correlation between NSE ratio and NSE serum concentration and curative effect, and then compared the evaluation performance of the two. RESULTS We found that increase in the NSE ratio is a risk factor for the progression of MNENOL. Compared with NSE, NSE ratio has a greater advantage in evaluating the effect of MNENOL. NSE ratio is related to the curative effect of NEN, and the correlation is better than that of NSE. When judging whether NEN has new metastasis, the NSE ratio shows a similar effect to NSE, and there is no significant difference between the two. CONCLUSION NSE ratio is more effective than NSE in evaluating the therapeutic effect of MNENOL, but it is not significantly different from NSE in terms of predicting new metastases.
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Affiliation(s)
- Jingbao Kan
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
| | - Ye Tian
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
| | - Yun Shao
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
| | - Haicheng Xu
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
| | - Xiaolin Li
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
| | - Qiyun Tang
- Neuroendocrine Neoplasm Center, Department of Geriatrics, Jiangsu Provincial People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China
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Asa SL, La Rosa S, Basturk O, Adsay V, Minnetti M, Grossman AB. Molecular Pathology of Well-Differentiated Gastro-entero-pancreatic Neuroendocrine Tumors. Endocr Pathol 2021; 32:169-191. [PMID: 33459926 DOI: 10.1007/s12022-021-09662-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/03/2021] [Indexed: 12/17/2022]
Abstract
Well differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal and pancreaticobiliary system are the most common neuroendocrine neoplasms. Studies of the molecular basis of these lesions have identified genetic mutations that predispose to familial endocrine neoplasia syndromes and occur both as germline events and in sporadic tumors. The mutations often involve epigenetic regulators rather than the oncogenes and tumor suppressors that are affected in other malignancies. Somatic copy number alterations and miRNAs have also been implicated in the development and progression of some of these tumors. The molecular profiles differ by location, but many are shared by tumors in other sites, including those outside the gastroenteropancreatic system. The approach to therapy relies on both the neuroendocrine nature of these tumors and the identification of specific alterations that can serve as targets for precision oncologic approaches.
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Affiliation(s)
- Sylvia L Asa
- Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
| | - Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Volkan Adsay
- Department of Pathology and Research Center for Translational Medicine (KUTTAM), Koç University Hospital, Istanbul, Turkey
| | - Marianna Minnetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Ashley B Grossman
- Green Templeton College, University of Oxford and ENETS Centre of Excellence, Royal Free Hospital, London, UK
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Borga C, Businello G, Murgioni S, Bergamo F, Martini C, De Carlo E, Trevellin E, Vettor R, Fassan M. Treatment personalization in gastrointestinal neuroendocrine tumors. Curr Treat Options Oncol 2021; 22:29. [PMID: 33641005 DOI: 10.1007/s11864-021-00825-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
The clinical scenario of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is continuously changing due to significant improvements in the definition of their molecular landscapes and the introduction of innovative therapeutic approaches. Many efforts are currently employed in the integration of the genetics/epigenetics and clinical information. This is leading to an improvement of tumor classification, prognostic stratification and ameliorating the management of patients based on a personalized approach.
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Affiliation(s)
- Chiara Borga
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Gianluca Businello
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Sabina Murgioni
- Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Francesca Bergamo
- Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Chiara Martini
- Endocrine-Metabolic Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Eugenio De Carlo
- Endocrine-Metabolic Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Elisabetta Trevellin
- Endocrine-Metabolic Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Roberto Vettor
- Endocrine-Metabolic Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
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Andreasi V, Partelli S, Muffatti F, Manzoni MF, Capurso G, Falconi M. Update on gastroenteropancreatic neuroendocrine tumors. Dig Liver Dis 2021; 53:171-182. [PMID: 32912771 DOI: 10.1016/j.dld.2020.08.031] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/20/2020] [Accepted: 08/21/2020] [Indexed: 02/07/2023]
Abstract
The incidence gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has dramatically risen over the last three decades, probably due to the increased detection of asymptomatic lesions. The diagnostic work-up for patients with suspected GEP-NENs is based on conventional imaging, endoscopy, pathology, and functional imaging, including 68Gallium-DOTATATE PET and 18F-FDG PET. The choice of the best treatment strategy should be based on the evaluation of tumor-related features and patient's characteristics. A conservative management, consisting of active surveillance or endoscopic resection, has been advocated for patients with small, incidentally discovered, nonfunctioning tumors without features of aggressiveness. On the other hand, surgery with lymphadenectomy, also with a minimally invasive approach, represents the gold standard for the curative treatment of localized disease. Moreover, surgical resection plays an important role also in the context of a multimodal treatment strategy for patients with advanced GEP-NENs. Finally, a wide range of medical therapies, comprising somatostatin analogues, peptide receptor radionuclide therapy, target therapies and several chemotherapy regimens, can be offered to patients with advanced GEP-NENs not amenable of surgical resection, according to the biological and molecular features of their disease.
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Affiliation(s)
- Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy
| | - Marco F Manzoni
- Endocrinology Unit, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Centre, OSR ENETS Center of Excellence IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
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Kurz S, Kollmeier J, Schmidt B, Schneider P, Utzig M, Grohé C. [Clinical Course of Typical and Atypical Carcinoids (bpNET): Evaluation of PneuNET Register Berlin Data for the Identification of Indicators for Prognosis Determination and Therapy Planning]. Pneumologie 2021; 75:276-283. [PMID: 33461225 DOI: 10.1055/a-1237-3617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
AIM Retrospective analysis of data from PneuNET registry to evaluate clinical follow up of patients with typical and atypical bronchopulmonary carcinoid (bpNET). METHOD Three lung cancer centres in Berlin included patients in the registry between 2007 and 2016. Inclusion criteria were: diagnosis of typical or atypical carcinoid, age > 18 years, follow-up for not less than 2 years. Frequency, gender, functional status, smoking status, localisation of the tumour, biomarker, diagnostic and therapeutic procedures and follow-up were evaluated. RESULTS Since 01. 01. 2007, 187 patients with bronchopulmonary carcinoid had been included in the registry. The ratio between TC and AC was 8:2. The median age was 65.4 years and 64 % of patients were women. 10.7 % of patients had pulmonary symptoms, 2 patients a carcinoid syndrome, no patient was detected with MEN-1-syndrome. 87.7 % of patients had undergone surgery, 69.5 % as lobectomy with systematic lymphadenectomy. Only 10 % of patients were diagnosed with Stage IV disease, with atypical carcinoid predominating Systemic therapies included chemotherapy, everolimus and somatostatin analogues. CONCLUSION Bronchopulmonary carcinoids are well differentiated tumours of the lung. The early stage diagnosis offers the possibility of local therapy with excellent prognosis. We have improved systemic treatment options with mTOR-inhibitor everolimus and somatostatin analogues also in advanced stage of the disease. Because of the rareness of this heterogenous group of tumours, it is meaningful to collect data systematically in order to have a standardised algorithm of diagnostic procedures and therapy assessment.
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Affiliation(s)
- S Kurz
- Evangelische Lungenklinik Berlin
| | - J Kollmeier
- Helios Klinikum Emil von Behring - Lungenklinik Heckeshorn
| | - B Schmidt
- DRK-Kliniken Berlin, Lungenklinik Mitte
| | | | - M Utzig
- DRK-Kliniken Berlin, Lungenklinik Mitte, Klinik für Thoraxchirurgie
| | - C Grohé
- Evangelische Lungenklinik Berlin
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A Comparison of Liver-Directed Therapy and Systemic Therapy for the Treatment of Liver Metastases in Patients with Gastrointestinal Neuroendocrine Tumors: Analysis of the California Cancer Registry. J Vasc Interv Radiol 2021; 32:393-402. [PMID: 33358144 DOI: 10.1016/j.jvir.2020.10.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 10/14/2020] [Accepted: 10/16/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To compare the outcomes of patients with gastrointestinal neuroendocrine tumor liver metastases treated with liver-directed therapy (LDT) to those treated with systemic therapy (ST) in a statewide cancer database. MATERIALS AND METHODS A retrospective study was performed of patients with metastatic gastrointestinal tract neuroendocrine tumors treated with either LDT or ST alone between the years 2000-2012 in the California Cancer Registry. Overall survival and disease-specific survival were assessed using multivariable Cox proportional hazards analysis and propensity score matching. RESULTS A total of 154 patients (ST, n = 87 and LDT, n = 67) were studied. The median overall survival and disease-specific survival for patients that received ST was 29 and 35 months versus 51 and >60 months for patients that received LDT. On multivariate analysis, LDT and the resection of the primary tumor were associated with improved survival (hazard ratio [HR] 0.52, P = .002; HR 0.43, P = .001). Non-white race, Medicaid/uninsured status, and the presence of lung metastases were associated with poor survival (HR 1.76, P = .014; HR 2.29, P = .009; and HR 1.79, P = .031). Propensity score matching demonstrated an improvement in disease-specific survival for LDT compared to ST (HR 0.53, P = .036). The improvement in overall survival on propensity score matching did not achieve statistical significance (HR 0.70, P = .199). CONCLUSIONS LDT is associated with improved overall and disease-specific survival as compared to ST in patients with gastrointestinal neuroendocrine tumor liver metastases. Further investigation is needed to determine whether combination or sequential treatment can improve outcomes in this population.
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Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Surg Oncol Clin N Am 2021; 30:39-55. [PMID: 33220808 PMCID: PMC7739028 DOI: 10.1016/j.soc.2020.08.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.
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Affiliation(s)
- Catherine G Tran
- Department of Surgery, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Scott K Sherman
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Chandrikha Chandrasekharan
- Department of Internal Medicine, Division of Hematology, Oncology and Blood and Marrow Transplantation, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - James R Howe
- Department of Surgery, Division of Surgical Oncology and Endocrine Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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Andreasi V, Partelli S, Muffatti F, Falconi M. New Surgical Strategies. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:113-128. [DOI: 10.1007/978-3-030-72830-4_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Gao HL, Wang WQ, Xu HX, Wu CT, Li H, Ni QX, Yu XJ, Liu L. Active surveillance in metastatic pancreatic neuroendocrine tumors: A 20-year single-institutional experience. World J Clin Cases 2020; 8:3751-3762. [PMID: 32953851 PMCID: PMC7479574 DOI: 10.12998/wjcc.v8.i17.3751] [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: 02/29/2020] [Revised: 05/09/2020] [Accepted: 08/09/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous and indolent; systemic therapy is not essential for every patient with metastatic PanNET. The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis, if the patient has stable disease. However, specific factors that influence surveillance were not mentioned. In addition, data regarding the period of active surveillance in patients with metastatic PanNET are lacking. AIM To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs (NF-PanNETs). METHODS Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled. Time to disease progression (TTP) and time to initiation of systemic therapy were determined. RESULTS Thirty-one (40.8%) patients had recurrent liver disease after R0 resection; 45 (59.2%) were diagnosed with liver metastasis. The median follow-up period was 42 mo and 90.7% patients were observed to have disease progression. The median TTP (mTTP) was 10 mo. Multivariate analysis showed that the largest axis of the liver metastasis > 5 mm (P = 0.04), non-resection of the primary tumor (P = 0.024), and T3-4 stage (P = 0.028) were associated with a shorter TTP. The mTTP in patients with no risk factors was 24 mo, which was significantly longer than that in patients with one (10 mo) or more (6 mo) risk factors (P < 0.001). A nomogram with three risk factors showed reasonable calibration, with a C-index of 0.603 (95% confidence interval: 0.47-0.74). CONCLUSION Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors, and other patients progressed rapidly without treatment. Further studies with a larger sample size and a control group are needed.
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Affiliation(s)
- He-Li Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Hua-Xiang Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Chun-Tao Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Hao Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Quan-Xing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Liang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
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