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Nordstrand MA, Lea D, Søreide JA. Incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): An updated systematic review of population-based reports from 2010 to 2023. J Neuroendocrinol 2025; 37:e70001. [PMID: 39933712 DOI: 10.1111/jne.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 12/28/2024] [Accepted: 01/28/2025] [Indexed: 02/13/2025]
Abstract
There is a general perception that the incidence of neuroendocrine neoplasms (NENs) has been increasing. Nevertheless, reports of actual population-based studies are scarce, and pertinent data from some geographical regions still need to be available. In this systematic literature review of population-based studies, we aimed to evaluate the available data to provide updated figures on the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Guided by the PRISMA 2020 statement reporting items for systematic reviews, this study conducted a systematic search using Ovid in the bibliographic databases Embase, Medline, and Web of Science Core Collection. Only incidence-reporting studies were included. In total, 847 articles were identified, and through a strict evaluation process using predefined inclusion and exclusion criteria, we found 19 papers that reported the general incidence of GEP-NENs from all sites. In addition, we considered another 15 papers that focused on the epidemiologic aspects of single-organ studies. While the incidence rates of GEP-NEN vary across similar countries, the general incidence of GEP-NEN has been increasing worldwide in recent decades. The incidence of GEP-NENs has increased worldwide over the last two decades, and reliable figures from new regions add to this pattern. Nevertheless, variations in the classification, grading, and reporting of GEP-NENs in various studies make direct comparisons difficult.
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Affiliation(s)
| | - Dordi Lea
- Department of Pathology, Stavanger University Hospital, Stavanger, Norway
| | - Jon Arne Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Zhang Q, Li Y, Xue C, Wang H, Li X. GlandSAM: Injecting Morphology Knowledge Into Segment Anything Model for Label-Free Gland Segmentation. IEEE TRANSACTIONS ON MEDICAL IMAGING 2025; 44:1070-1082. [PMID: 39378253 DOI: 10.1109/tmi.2024.3476176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/10/2024]
Abstract
This paper presents a label-free gland segmentation, GlandSAM, which achieves comparable performance with supervised methods while no label is required during its training or inference phase. We observe that the Segment Anything model produces sub-optimal results on gland dataset: It either over-segments a gland into many fractions or under-segments the gland regions by confusing many of them with the background, due to the complex morphology of glands and lack of sufficient labels. To address this challenge, our GlandSAM innovatively injects two clues about gland morphology into SAM to guide the segmentation process: (1) Heterogeneity within glands and (2) Similarity with the background. Initially, we leverage the clues to decompose the intricate glands by selectively extracting a proposal for each gland sub-region of heterogeneous appearances. Then, we inject the morphology clues into SAM in a fine-tuning manner with a novel morphology-aware semantic grouping module that explicitly groups the high-level semantics of gland sub-regions. In this way, our GlandSAM could capture comprehensive knowledge about gland morphology, and produce well-delineated and complete segmentation results. Extensive experiments conducted on the GlaS dataset and the CRAG dataset reveal that GlandSAM outperforms state-of-the-art label-free methods by a significant margin. Notably, our GlandSAM even surpasses several fully-supervised methods that require pixel-wise labels for training, which highlights the remarkable performance and potential of GlandSAM in the realm of gland segmentation.
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Massironi S. Unraveling the Microbiome's Role in Neuroendocrine Neoplasms: A New Perspective. Neuroendocrinology 2024; 114:977-980. [PMID: 39406190 DOI: 10.1159/000541678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 09/26/2024] [Indexed: 11/12/2024]
Affiliation(s)
- Sara Massironi
- Department of Medicine and Surgery, University of Vita-Salute San Raffaele, Milan, Italy
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Peng Y, Xu B, Zhang F, Wu R, Tong S, Mao Z. Incidence, survival, and prognostic nomogram of patients with small intestinal neuroendocrine tumors: A SEER population-based study. Medicine (Baltimore) 2024; 103:e39616. [PMID: 39287239 PMCID: PMC11404879 DOI: 10.1097/md.0000000000039616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/19/2024] Open
Abstract
Small intestinal neuroendocrine tumors (SI-NETs) are a group of rare and significantly heterogeneous tumors with limited research currently available. This study aimed to investigate the incidence, survival, and prognostic factors of SI-NETs. We selected data from the surveillance, epidemiology, and end results (SEER) database between 2000 and 2019 and evaluated the incidence trend of SI-NETs during this period. We utilized the Kaplan-Meier method to examine the association between clinical variables and survival rates. Based on the multivariable Cox regression analysis results, we developed a nomogram to predict the 1-, 2-, and 3-year cancer-specific survival (CSS) of SI-NETs patients. We evaluated the consistency, accuracy, and clinical utility of the nomogram by drawing calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) curves. The incidence of SI-NETs showed an upward trend in recent years. Age, grade, T stage, M stage, and primary tumor surgery were independent risk factors for CSS in SI-NETs patients. The nomogram model based on these risk factors showed high accuracy and clinical benefit. SI-NETs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in SI-NETs patients, which may benefit clinical decision-making.
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Affiliation(s)
- Yao Peng
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Mortagy M, El Asmar ML, Chandrakumaran K, Ramage J. Sex Differences in the Survival of Patients with Neuroendocrine Neoplasms: A Comparative Study of Two National Databases. Cancers (Basel) 2024; 16:2376. [PMID: 39001438 PMCID: PMC11240657 DOI: 10.3390/cancers16132376] [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: 06/01/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are increasing in incidence globally. Previous analysis of the UK cancer database (National Cancer Registration and Analysis Service (NCRAS)) showed a notable female survival advantage in most tumour sites. This study aims to compare NCRAS to the Surveillance, Epidemiology, and End Results Program (SEER) to validate these results using the same statistical methods. METHODS A total of 14,834 and 108,399 patients with NENs were extracted from NCRAS and SEER, respectively. Sixty-months survival for both males and females for each anatomical site of NENs were calculated using restricted mean survival time (RMST) and Kaplan-Meier Survival estimates. The sixty-month RMST female survival advantage (FSA) was calculated. RESULTS FSA was similar in NCRAS and SEER. The highest FSA occurred in lung and stomach NENs. CONCLUSIONS The data from SEER confirm the findings published by NCRAS. Female survival advantage remains unexplained.
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Affiliation(s)
- Mohamed Mortagy
- Hampshire Hospitals NHS Foundation Trust, Winchester SO22 5DG, UK
- Internal Medicine Department, St. George University School of Medicine, West Indies, Grenada
| | - Marie Line El Asmar
- Gastroenterology Department, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
| | - Kandiah Chandrakumaran
- Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
| | - John Ramage
- Gastroenterology Department, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
- Faculty of Health and Wellbeing, University of Winchester, Winchester SO22 4NR, UK
- Kings Health Partners Neuroendocrine Centre, London SE1 9RT, UK
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Ruggeri RM, Altieri B, Razzore P, Retta F, Sperti E, Scotto G, Brizzi MP, Zumstein L, Pia A, Lania A, Lavezzi E, Nappo G, Laffi A, Albertelli M, Boschetti M, Hasballa I, Veresani A, Prinzi N, Pusceddu S, Oldani S, Nichetti F, Modica R, Minotta R, Liccardi A, Cannavale G, Grossrubatscher EM, Tarsitano MG, Zamponi V, Zatelli MC, Zanata I, Mazzilli R, Appetecchia M, Davì MV, Guarnotta V, Giannetta E, La Salvia A, Fanciulli G, Malandrino P, Isidori AM, Colao A, Faggiano A. Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study. J Endocrinol Invest 2024; 47:959-971. [PMID: 37837555 DOI: 10.1007/s40618-023-02213-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 09/25/2023] [Indexed: 10/16/2023]
Abstract
BACKGROUND The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. PURPOSE To evaluate gender differences in clinical presentation and outcome of CaS. METHODS Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. RESULTS Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p = 0.002, and 3.7%, p = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p = 0.044; 6.7% vs 31.5%, p = 0.001; 50.9% vs. 26.7%, p = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p = 0.04), but no differences in terms of PFS (p = 0.51) and OS (p = 0.64) were found between gender. CONCLUSIONS In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.
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Affiliation(s)
- R M Ruggeri
- Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV, University of Messina, 98125, Messina, Italy
| | - B Altieri
- Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Würzburg, Würzburg, Germany
| | - P Razzore
- SC Endocrinologia, Diabetologia e Malattie del Metabolismo, AO Ordine Mauriziano di Torino, Largo Turati, 62 10128, Turin, Italy
| | - F Retta
- SC Endocrinologia, Diabetologia e Malattie del Metabolismo, AO Ordine Mauriziano di Torino, Largo Turati, 62 10128, Turin, Italy
| | - E Sperti
- SCDU Oncologia, AO Ordine Mauriziano di Torino, Largo Turati, 62 10128, Turin, Italy
| | - G Scotto
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Turin, Italy
| | - M P Brizzi
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Turin, Italy
| | - L Zumstein
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Turin, Italy
| | - A Pia
- Internal Medicine, Department of Clinical and Biological Sciences, S. Luigi Hospital, University of Turin, Turin, Italy
| | - A Lania
- Department of Biomedical Sciences, Humanitas University, 20089, Pieve Emanuele, Italy
- Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, 20089, Rozzano, Italy
| | - E Lavezzi
- Endocrinology, Diabetology and Andrology Unit, IRCCS Humanitas Research Hospital, 20089, Rozzano, Italy
| | - G Nappo
- Department of Biomedical Sciences, Humanitas University, 20089, Pieve Emanuele, Italy
- Pancreas Surgery Unit, IRCCS Humanitas Research Hospital, 20089, Rozzano, Italy
| | - A Laffi
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - M Albertelli
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 16132, Genoa, Italy
- Endocrinology Unit, IRCCC Ospedale Policlinico San Martino, 16132, Genoa, Italy
| | - M Boschetti
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 16132, Genoa, Italy
- Endocrinology Unit, IRCCC Ospedale Policlinico San Martino, 16132, Genoa, Italy
| | - I Hasballa
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 16132, Genoa, Italy
| | - A Veresani
- Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 16132, Genoa, Italy
| | - N Prinzi
- Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy
- First Department of Internal Medicine, San Matteo Hospital Foundation, Padua, Italy
| | - S Pusceddu
- Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy
| | - S Oldani
- Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy
| | - F Nichetti
- Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy
| | - R Modica
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - R Minotta
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - A Liccardi
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | - G Cannavale
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
| | | | - M G Tarsitano
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - V Zamponi
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, ENETS Center of Excellence, Rome, Italy.
| | - M C Zatelli
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - I Zanata
- Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - R Mazzilli
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, ENETS Center of Excellence, Rome, Italy
| | - M Appetecchia
- Oncological Endocrinology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - M V Davì
- Department of Medicine, Section of Endocrinology, University and Hospital Trust of Verona, Verona, Italy
| | - V Guarnotta
- Dipartimento di Promozione della Salute, Materno-Infantile, Medicina Interna e Specialistica di Eccellenza "G. D'Alessandro" (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, 90127, Palermo, Italy
| | - E Giannetta
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - A La Salvia
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144, Rome, Italy
| | - G Fanciulli
- Neuroendocrine Tumour Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari-Endocrine Unit, AOU Sassari, Sassari, Italy
| | - P Malandrino
- Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania and Garibaldi, Nesima Medical Center, Catania, Italy
| | - A M Isidori
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - A Colao
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
- UNESCO Chair on Health Education and Sustainable Development, Federico II University, 80138, Naples, Italy
| | - A Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, ENETS Center of Excellence, Rome, Italy
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7
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Panzuto F, Partelli S, Campana D, de Braud F, Spada F, Cives M, Tafuto S, Bertuzzi A, Gelsomino F, Bergamo F, Marcucci S, Mastrangelo L, Massironi S, Appetecchia M, Filice A, Badalamenti G, Bartolomei M, Amoroso V, Landoni L, Rodriquenz MG, Valente M, Colao A, Isidori A, Fanciulli G, Bollina R, Ciola M, Butturini G, Marconcini R, Arvat E, Cinieri S, Berardi R, Baldari S, Riccardi F, Spoto C, Giuffrida D, Gattuso D, Ferone D, Rinzivillo M, Bertani E, Versari A, Zerbi A, Lamberti G, Lauricella E, Pusceddu S, Fazio N, Dell'Unto E, Marini M, Falconi M. Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database. Endocrine 2024; 84:42-47. [PMID: 38175391 PMCID: PMC10987336 DOI: 10.1007/s12020-023-03649-4] [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: 11/15/2023] [Accepted: 12/07/2023] [Indexed: 01/05/2024]
Abstract
Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).
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Affiliation(s)
- Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy.
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Davide Campana
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, ENETS Center of Excellence, Milan, Italy
| | - Francesca Spada
- Gastrointestinal and Neuroendocrine Tumors Oncology Unit - ENETS Center of Excellence, European Institute of Oncology (IEO) - IRCCS, Milan, Italy
| | - Mauro Cives
- Dipartimento Interdisciplinare di Medicina, Università di Bari "Aldo Moro", Bari, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, I.R.C.C.S. - Fondazione "G. Pascale", ENETS Center of Excellence, Napoli, Italy
| | - Alexia Bertuzzi
- Sezione Sarcomi/NET e Oncologia del Giovane Adulto (AYA-Adolescent Young Adult) Humanitas Research Hospital-IRCCS Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Fabio Gelsomino
- Department of Oncology and Hematology, Division of Oncology, University Hospital of Modena, Modena, Italy
| | | | - Stefano Marcucci
- Department of Surgery & Hepato-Biliary and Pancreatic Unit Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| | - Laura Mastrangelo
- UO Chirurgia Generale e d'Urgenza IRCCS Azienda Ospedaliera Universitaria Sant'Orsola Malpighi c/o Ospedale Maggiore, Bologna, Italy
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, and University of Milano-Bicocca, School of Medicine, Monza, Italy
| | - Marialuisa Appetecchia
- Oncological Endocrinology Unit, Regina Elena National Cancer Institutre - IFO IRCCS, Roma, Italy
| | - Angelina Filice
- Servizio di Medicina Nucleare, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Giuseppe Badalamenti
- Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Mirco Bartolomei
- Nuclear Medicine Unit, Azienda Ospedaliera Universitaria-Ferrara, Ferrara, Italy
| | - Vito Amoroso
- Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia at Spedali Civili Hospital, Brescia, Italy
| | - Luca Landoni
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, ENETS Center of Excellence, Verona, Italy
| | - Maria Grazia Rodriquenz
- Oncology Unit - Ospedale IRCCS Casa Sollievo della Sofferenza - San Giovanni Rotondo, Foggia, Italy
| | - Monica Valente
- Center for Immuno-Oncology, Oncology Department, University Hospital of Siena, Siena, Italy
| | - Annamaria Colao
- Department of Endocrinology University of Naples, Azienda Ospedaliera Universitaria "Federico II", ENETS CEnter of Excellence, Napoli, Italy
| | - Andrea Isidori
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Giuseppe Fanciulli
- Endocrine Oncology Program, Endocrine Unit, University Hospital (AOU) of Sassari, Sassari, Italy
| | | | | | | | - Riccardo Marconcini
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Emanuela Arvat
- Oncological Endocrinology Unit, Department of Medical Sciences University of Turin, Turin, Italy
| | | | - Rossana Berardi
- Department of Medical Oncology, Università Politecnica Delle Marche, AOU Ospedali Riuniti Delle Marche, Ancona, Italy
| | - Sergio Baldari
- Nuclear Medicine Unit, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | | | - Chiara Spoto
- Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy
| | - Dario Giuffrida
- Medical Oncology Department, Istituto Oncologico del Mediterraneo, Viagrande, Catania, Italy
| | | | - Diego Ferone
- Endocrinology Unit, Department of Internal Medicine & Medical Specialties (DiMI), IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Maria Rinzivillo
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - Emilio Bertani
- Digestive Surgery, European Institute of Oncology IRCCS, ENETS Center of Excellence, Milan, Italy
| | - Annibale Versari
- Servizio di Medicina Nucleare, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Alessandro Zerbi
- Humanitas Research Hospital -IRCCS, Pancreatic Surgery Unit, Rozzano, and Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy
| | - Giuseppe Lamberti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Eleonora Lauricella
- Dipartimento Interdisciplinare di Medicina, Università di Bari "Aldo Moro", Bari, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori Di Milano, ENETS Center of Excellence, Milan, Italy
| | - Nicola Fazio
- Gastrointestinal and Neuroendocrine Tumors Oncology Unit - ENETS Center of Excellence, European Institute of Oncology (IEO) - IRCCS, Milan, Italy
| | - Elisabetta Dell'Unto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - Marco Marini
- IMT School for Advanced Studies Lucca, Lucca, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
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8
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Johansen SU, Hansen T, Nordborg A, Meyer R, Goll R, Florholmen J, Jensen E. Plasma tryptophan pathway metabolites quantified by liquid chromatography-tandem mass spectrometry as biomarkers in neuroendocrine tumor patients. J Neuroendocrinol 2024; 36:e13372. [PMID: 38361341 DOI: 10.1111/jne.13372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/21/2023] [Accepted: 01/11/2024] [Indexed: 02/17/2024]
Abstract
A good and accessible biomarker is of great clinical value in neuroendocrine tumor (NET) patients, especially considering its frequently indolent nature and long-term follow-up. Plasma chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are currently used as biomarkers in NET, but their sensitivity and specificity are restricted. 5-HIAA is the main metabolite of serotonin, an important neurotransmitter of the tryptophan pathway. The aim of this study is to estabish a sensitive and accurate method for the quantification of tryptophan pathway metabolites in plasma. We further aimed to evaluate its utility as a clinical tool in NET disease. We obtained plasma samples from NET patients and healthy controls recruited from the University Hospital of North Norway, Tromsø. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and eight metabolites of the tryptophan pathway were quantified. We included 130 NET patients (72/130 small intestinal [SI] NET, 35/130 pancreatic NET, 23/130 other origin) and 20 healthy controls. In the SI-NET group, 26/72 patients presented with symptoms of carcinoid syndrome (CS). We found that combining tryptophan metabolites into a serotonin/kynurenine pathway ratio improved diagnostic sensitivity (92.3%) and specificity (100%) in detecting CS patients from healthy controls compared with plasma 5-HIAA alone (sensitivity 84.6%/specificity 100%). Further, a clinical marker based on the combination of plasma serotonin, 5-HIAA, and 5OH-tryptophan, increased diagnostic capacity identifying NET patients with metastasized disease from healthy controls compared with singular plasma 5-HIAA, serotonin, or CgA. In addition, this marker was positive in 61% of curatively operated SI-NET patients compared with only 10% of healthy controls (p < .001). Our results indicate that simultaneous quantification of several tryptophan metabolites in plasma, using LC-MS/MS, may represent a clinically useful diagnostic tool in NET disease.
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Affiliation(s)
- S U Johansen
- Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway
- Medical Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - T Hansen
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway
- Department of Pharmacy, UiT the Arctic University of Norway, Tromsø, Norway
| | - A Nordborg
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway
| | - R Meyer
- Medical Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - R Goll
- Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway
- Medical Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - J Florholmen
- Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway
- Medical Gastroenterology, Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - E Jensen
- Department of Pharmacy, UiT the Arctic University of Norway, Tromsø, Norway
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9
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O'Reilly E, Lao L, Woodhouse B, Sharples K, Print C, Lawrence B. Palliative radiotherapy is effective for both well- and poorly differentiated neuroendocrine neoplasms. J Med Imaging Radiat Oncol 2024; 68:94-102. [PMID: 37898955 DOI: 10.1111/1754-9485.13597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 10/05/2023] [Indexed: 10/31/2023]
Abstract
INTRODUCTION The outcomes of palliative radiation therapy (RT) for neuroendocrine neoplasms (NEN) are seldom reported. We investigated outcomes following palliative radiotherapy in a cohort of patients with NENs. We hypothesised that well-differentiated NEN will be less likely to have a clinical response than poorly differentiated NEN. METHODS Patients who received at least one course of palliative RT were identified using the New Zealand NETwork! Registry. Patients with Merkel cell carcinoma, pulmonary small cell carcinoma or asymptomatic patients were excluded. Clinical response to RT within 90 days and overall survival were analysed alongside clinical variables (fractionation, RT site, tumour differentiation and tumour primary site). RESULTS The cohort comprised 79 patients, with 147 courses of palliative RT delivered. Clinical response was measurable for 100 courses, with clinical response rate of 76%. A course delivered to a well-differentiated NEN was associated with 2.02-fold (95% CI 0.67, 6.12; P = 0.21) increase in odds of a clinical response compared to a poorly differentiated NEN. Median overall survival from the first fraction of RT was 94 days (95% CI 80, 138 days). Overall survival was higher in well-differentiated NEN than in poorly differentiated NEN (HR 0.2, 95% CI 0.10-0.40, P-value < 0.001); 30-day mortality was 7%. There were significantly reduced odds of clinical response for non-bone sites, and for courses >10 fractions compared to a single fraction. CONCLUSION Palliative RT is an appropriate option for management of symptoms in patients with both well- and poorly differentiated metastatic NEN.
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Affiliation(s)
- Eileen O'Reilly
- Radiation Oncology, Te Whatu Ora - Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Louis Lao
- Radiation Oncology, Te Whatu Ora Te Toka Tumai Auckland, Waipapa Taumata Rau/The University of Auckland, Auckland, New Zealand
| | - Braden Woodhouse
- Cancer Trials New Zealand, Waipapa Taumata Rau/The University of Auckland, Auckland, New Zealand
| | - Katrina Sharples
- Cancer Trials New Zealand, University of Otago, Dunedin, New Zealand
| | - Cris Print
- Department of Molecular Medicine and Pathology, Waipapa Taumata Rau/The University of Auckland, Auckland, New Zealand
| | - Ben Lawrence
- Medical Oncology, Te Whatu Ora Te Toka Tumai Auckland, Waipapa Taumata Rau/The University of Auckland, Auckland, New Zealand
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10
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Edfeldt K, Hellman P, Granberg D, Lagergren P, Thiis-Evensen E, Sundin A, Andersson C. Improved health-related quality of life during peptide receptor radionuclide therapy in patients with neuroendocrine tumours. J Neuroendocrinol 2023; 35:e13342. [PMID: 37807573 DOI: 10.1111/jne.13342] [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: 10/14/2022] [Revised: 09/04/2023] [Accepted: 09/18/2023] [Indexed: 10/10/2023]
Abstract
Neuroendocrine tumours (NETs) can arise in different locations in the body, and may give rise to hormonal symptoms, which amongst other factors may affect patients' health-related quality of life (HRQoL). Up to four cycles of peptide receptor radionuclide therapy (PRRT) have been shown effective for symptom alleviation and prolonging progression-free survival. The aim of this study was to assess the patient's perspective regarding changes in their HRQoL during PRRT. HRQoL was assessed using the questionnaires for cancer in general, EORTC QLQ-C30, and the gastrointestinal NET-specifically EORTC QLQ-GINET21. Patients with NET (n = 204) rated their HRQoL before PRRT cycles one and four. The medical records of patients were reviewed and their HRQoL was compared to a matched reference population (n = 4910). HRQoL was found to improve during PRRT in aspects of global quality of life; role, social, and emotional functioning, and multiple symptom relief. Potential risk groups for worse HRQoL during PRRT were patients with overweight (BMI >25) who completed four cycles of PRRT and older patients (>65 years old). In conclusion, we found that PRRT improves HRQoL in patients with NETs. The results of this study may be used to improve person-centred care.
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Affiliation(s)
- Katarina Edfeldt
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Dan Granberg
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Pernilla Lagergren
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Espen Thiis-Evensen
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Anders Sundin
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Camilla Andersson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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11
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Helderman NC, Suerink M, Kilinç G, van den Berg JG, Nielsen M, Tesselaar ME. Relation between WHO Classification and Location- and Functionality-Based Classifications of Neuroendocrine Neoplasms of the Digestive Tract. Neuroendocrinology 2023; 114:120-133. [PMID: 37690447 PMCID: PMC10836754 DOI: 10.1159/000534035] [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: 03/27/2023] [Accepted: 08/21/2023] [Indexed: 09/12/2023]
Abstract
Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.
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Affiliation(s)
- Noah C. Helderman
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Manon Suerink
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Gül Kilinç
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands
| | - José G. van den Berg
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Maartje Nielsen
- Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
| | - Margot E.T. Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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12
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Søreide K, Hallet J, Jamieson NB, Stättner S. Optimal surgical approach for digestive neuroendocrine neoplasia primaries: Oncological benefits versus short and long-term complications. Best Pract Res Clin Endocrinol Metab 2023; 37:101786. [PMID: 37328324 DOI: 10.1016/j.beem.2023.101786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
The rising incidence and the accumulating prevalence of neuroendocrine neoplasia (NEN) in the population makes this a common, prevalent and a clinically relevant disease group. Surgical resection represents the only potentially curative treatment for digestive NENs. Thus, resection should in principle be considered for all patients with NEN, although taking the patients age, relevant comorbidity, and performance status into account for operability. Patients with insulinomas, NEN of the appendix and rectal NENs are usually cured by surgery alone. However, less than a third of patients are amendable to curative surgery alone at time of diagnosis. Furthermore, recurrence is common and may occur years after primary surgery, hence the long follow-up time recommended in most NENs (>10 years). As many patients with NENs present with locoregional or metastatic disease, there is considerable debate regarding the role of debulking surgery in these settings. However, good long-term survival can be achieved in a considerable proportion of patients, with 50-70% alive up to 10 years after surgery. Location and grade are the main determinants of long-term survival. Here we present considerations to surgery for primary neuroendocrine tumors in the digestive tract.
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Affiliation(s)
- Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway; Gastrointestinal Translational Research Group, Laboratory for Molecular Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Julie Hallet
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Susan Leslie Clinic for Neuroendocrine Tumors - Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Nigel B Jamieson
- Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, Scotland, UK
| | - Stefan Stättner
- Department of General, Visceral and Vascular Surgery, Salzkammergutklinikum, Vöcklabruck, Austria
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13
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Ooki A, Osumi H, Fukuda K, Yamaguchi K. Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma. Cancer Metastasis Rev 2023; 42:1021-1054. [PMID: 37422534 PMCID: PMC10584733 DOI: 10.1007/s10555-023-10121-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 06/16/2023] [Indexed: 07/10/2023]
Abstract
Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeutic option for recurrent or metastatic GEP-NEC patients, the clinical benefits are limited and associated with a poor prognosis, indicating the clinically urgent need for effective therapeutic agents. The clinical development of molecular-targeted therapies has been hampered due to the rarity of GEP-NECs and the paucity of knowledge on their biology. In this review, we summarize the biology, current treatments, and molecular profiles of GEP-NECs based on the findings of pivotal comprehensive molecular analyses; we also highlight potent therapeutic targets for future precision medicine based on the most recent results of clinical trials.
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Affiliation(s)
- Akira Ooki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Hiroki Osumi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koshiro Fukuda
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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14
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Folkestad O, Hauso Ø, Mjønes P, Fougner R, Wasmuth HH, Fossmark R. Survival Trends in Patients with Small Intestinal Neuroendocrine Tumours-A Cohort Study in Central Norway. Cancers (Basel) 2023; 15:3272. [PMID: 37444383 DOI: 10.3390/cancers15133272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Improved surgical resection and oncological treatment, or an earlier diagnosis may increase survival in small intestinal neuroendocrine tumours (SI-NETs), but only few studies have examined survival trends. We aimed to examine the trend in overall survival and associated factors in SI-NET patients. All patients with SI-NETs at a regional hospital from June 2005 to December 2021 (n = 242) were identified, and the cohort was divided in half, constituting a first period (until November 2012) and a second period (from November 2012). Disease and treatment characteristics, including European Neuroendocrine Tumour Society (ENETS) stage, surgery, oncological treatment and survival, were recorded. The majority (n = 205 (84.7%)) were treated surgically and surgery was considered curative in 137 (66.8%) patients. Median survival was longer in the second period (9.0 years 95% CI 6.4-11.7 in the first period vs. median not reached in the second period, p = 0.014), with 5-year survival rates of 63.5% and 83.5%, respectively. ENETS stage and oncological treatment did not differ between the periods, but factors associated with surgical quality, such as lymph node harvest and resection of multiple SI-NETs, were significantly higher in the second period. Age, ENETS stage, time period and tumour resection were independently associated with survival in a multivariate analysis.
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Affiliation(s)
- Oddry Folkestad
- Department of Gastrointestinal Surgery, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Gastrointestinal Surgery, Vestfold Hospital Thrust, 3103 Tønsberg, Norway
| | - Øyvind Hauso
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
| | - Patricia Mjønes
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Pathology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidun Fougner
- Department of Radiology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Hans H Wasmuth
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
| | - Reidar Fossmark
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
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15
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Sun D, Ren Z, Xu E, Cai S, Qi Z, Chen Z, Liu J, Shi Q, Zhou P, Zhong Y. Long-term clinical outcomes of endoscopic submucosal dissection in rectal neuroendocrine tumors based on resection margin status: a real-world study. Surg Endosc 2023; 37:2644-2652. [PMID: 36380122 DOI: 10.1007/s00464-022-09710-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 10/11/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Endoscopic submucosal dissection (ESD) has been widely adopted in treating rectal neuroendocrine tumors (NETs). However, clinical outcomes in rectal NETs after ESD with different resection margin status remain scanty, particularly in patients with positive resection margins. This study aimed to evaluate the long-term clinical outcomes of ESD in rectal NET based on the resection margin status. METHODS This retrospective study included 436 patients diagnosed with rectal NET who had undergone ESD. Clinical data, including age, sex, tumor size, stage, invasion, and the resection margin status, were collected. Further, the patients were assessed for complications, recurrence, distant metastasis, and long-term outcomes. RESULTS Among all 436 patients, 395 patients had their primary ESD in our hospital. Complete resection was achieved in 319 patients. Patients who did not achieve complete resection opted for follow-up (n = 73), salvage surgery (n = 1) and salvage ESD (n = 2). Another 41 had their primary ESD in other hospital with incomplete resection and had salvage ESD in our hospital. All 436 patients had a median follow-up period of 61.4 months (range 33.4-125.3 months). During the follow-up period, two patients developed recurrences, while three patients developed metastasis. There were no significant differences in the 5-year progression-free survival and overall survival between patients with incomplete resection opting for follow-up compared to the other two groups (P = 0.5/0.8). However, the complication rates were significantly higher in patients who received salvage ESD. CONCLUSION This study demonstrated that positive resection margins have no influence on survival in patients with rectal NET treated using ESD.
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Affiliation(s)
- Di Sun
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Department of Breast Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
| | - Zhong Ren
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Enpan Xu
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Shilun Cai
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Zhipeng Qi
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Zhanghan Chen
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Jingyi Liu
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China
| | - Qiang Shi
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
| | - Pinghong Zhou
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
| | - Yunshi Zhong
- Endoscopy Center, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
- Endoscopy Research Institute of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
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16
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White BE, Russell B, Remmers S, Rous B, Chandrakumaran K, Wong KF, Van Hemelrijck M, Srirajaskanthan R, Ramage JK. Sex Differences in Survival from Neuroendocrine Neoplasia in England 2012–2018: A Retrospective, Population-Based Study. Cancers (Basel) 2023; 15:cancers15061863. [PMID: 36980749 PMCID: PMC10046836 DOI: 10.3390/cancers15061863] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 03/05/2023] [Accepted: 03/15/2023] [Indexed: 03/22/2023] Open
Abstract
Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.
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Affiliation(s)
- Benjamin E. White
- Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
- Correspondence: ; Tel.: +44-1256-473202
| | - Beth Russell
- Translational Oncology and Urology Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London WC2R 2LS, UK
| | - Sebastiaan Remmers
- Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Brian Rous
- NHS Digital, 7 and 8 Wellington Place, Leeds LS1 4AP, UK
| | - Kandiah Chandrakumaran
- Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
| | - Kwok F. Wong
- NHS Digital, 7 and 8 Wellington Place, Leeds LS1 4AP, UK
| | - Mieke Van Hemelrijck
- Translational Oncology and Urology Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London WC2R 2LS, UK
| | | | - John K. Ramage
- Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke RG24 9NA, UK
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17
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Thiis-Evensen E, Boyar Cetinkaya R. Incidence and prevalence of neuroendocrine neoplasms in Norway 1993-2021. J Neuroendocrinol 2023; 35:e13264. [PMID: 36988112 DOI: 10.1111/jne.13264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 02/06/2023] [Accepted: 03/09/2023] [Indexed: 03/19/2023]
Abstract
The incidence of neuroendocrine neoplasms (NENs) has increased over the last decades. The prevalence of NENs has to a lesser extent been previously reported. We wanted to study the trends in incidence and prevalence of NEN in Norway from 1993 to 2021 through the Cancer Registry of Norway. This registry, which covers the whole population, has been found to be 99% complete. The neoplasms were classified as neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). From 1993 to 2021 altogether 10.288 NETs and 13,982 (1.756 outside the lungs) NECs were diagnosed. The incidence of NETs increased from 3.72 to 9.97 per 100,000 per year, corresponding to a 268% increase, p < .001. The largest increase in incidence for NETs was found for pancreas (338%), lung (330%) and small intestine (303%). For NECs there was no change in the incidence, from 9.74 to 9.95 per 100,000 per year, p = .4, but there was an increase in the incidence of NECs originating from the skin (Merkel cell carcinoma) (287%), p < .001, and the GI tract (200%), p = .03. There were no changes in stage distribution at diagnosis for NETs and NECs. The prevalence for NENs increased 666% during the study period, NETs increased from 10.77 to 99.37 per 100.000 (927%), p < .001. For NECs the increase was from 7.4 to 21.56 per 100.000 (291%), p < .001. GI-NECs increased the most from 0.005 to 0.94 (1880%), p = .002. In conclusion, there was a substantial increase in incidence and prevalence of neuroendocrine neoplasms in Norway from 1993 to 2021. This is the first study to report complete prevalence of NENs for a whole nation.
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Affiliation(s)
- Espen Thiis-Evensen
- Center for Neuroendocrine Tumors, Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Sira L, Zsíros N, Bidiga L, Barna S, Kanyári Z, Nagy EB, Guillaume N, Wild D, Rázsó K, Andó S, Balogh I, Nagy EV, Balogh Z. Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies. Front Endocrinol (Lausanne) 2023; 14:1095815. [PMID: 36923225 PMCID: PMC10008953 DOI: 10.3389/fendo.2023.1095815] [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: 11/11/2022] [Accepted: 02/10/2023] [Indexed: 03/03/2023] Open
Abstract
Background Splanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition. Case report Here we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.
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Affiliation(s)
- Lívia Sira
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Noémi Zsíros
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - László Bidiga
- Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Sándor Barna
- Department of Nuclear Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zsolt Kanyári
- Department of Surgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Edit B. Nagy
- Department of Radiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Nicolas Guillaume
- Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland
| | - Damian Wild
- Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland
| | - Katalin Rázsó
- Division of Haematology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Szilvia Andó
- Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - István Balogh
- Division of Clinical Genetics, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Endre V. Nagy
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Zoltán Balogh
- Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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19
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Hummelshøj NE, Gronbaek H, Bager P, Tabaksblat E, Dam G. Fatigue and quality of life in patients with neuroendocrine neoplasia. Scand J Gastroenterol 2023; 58:45-53. [PMID: 35850607 DOI: 10.1080/00365521.2022.2100228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Neuroendocrine Neoplasms (NEN) are rare tumours arising in the gastro-intestinal tract or lungs. Poor health related quality of life (HRQoL) is associated with the carcinoid syndrome (CS), but fatigue is also important. We aimed to quantify HRQoL and fatigue in out-patients with NEN. METHODS In a cross-sectional study, we included 231 patients with NEN (G1-G3). We used pre-validated questionnaires MFI-20, EQ-5D-5L and 85% responded. We collected clinical, biochemical, imaging, and pathology data from Electronic Patient files. Normative values for fatigue and HRQoL were derived from background populations. RESULTS Median age was 68 years (range 21-91) and 52% were male. Patients with NEN reported more fatigue and worse HRQoL compared to the background population (p < .05). Cured patients reported higher HRQoL than patients with current disease, and patients with high grade neoplasms (G2-G3) reported more anxiety and depression compared to patients with low grade G1 disease (p < .05). The CS resulted in a 9% relative loss in Quality Adjusted Life Years compared to patients without CS. (p < .05). More than 50% of patients with CS reported problems with usual activities, pain/discomfort, and anxiety/depression. Overall, 36% of patients with NEN were fatigued and 92% of these had psychological fatigue. Younger patients (<65 years) experienced more fatigue than older patients (p < .05). CONCLUSION Patients with NEN report significantly lower HRQoL and more fatigue compared to the background population. Especially, patients with CS had pain, discomfort, anxiety, and depression and a relative reduction in HRQoL. However, compared to other cancer types, patients with NEN experience less fatigue.
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Affiliation(s)
| | - Henning Gronbaek
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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20
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Long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based study. Eur J Cancer 2022; 172:252-263. [PMID: 35803176 DOI: 10.1016/j.ejca.2022.06.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 05/30/2022] [Accepted: 06/02/2022] [Indexed: 12/19/2022]
Abstract
BACKGROUND Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) comprise a group of rare malignant tumours with heterogeneous behaviour. This study aimed to assess long-term survival and prognostic factors associated with survival, in order to optimise counselling. PATIENTS AND METHODS This population-based study included all GEP-NENs diagnosed between 1989 and 2016 in the Netherlands, selected from the Netherlands Cancer Registry. Overall survival (OS) and relative survival (RS) were calculated. A Cox Proportional Hazard analysis was used to identify prognostic factors (gender, age, tumour stage, location and treatment) for OS. Analyses were stratified by metastatic disease status and tumour grade. RESULTS In total, 9697 patients were included. In grade 1, 2 and 3 non-metastatic GEP-NENs (N = 6544), 5-year OS and RS were 81% and 88%, 78% and 83%, and 26% and 30%, respectively. In grade 1 non-metastatic GEP-NENs 10-year OS and RS were 68% and 83%. In grade 1, 2 and 3 metastatic GEP-NENs (N = 3153), 5-year OS and RS rates were 47% and 52%, 38% and 41%, and 5% and 5%, respectively. The highest (relative) survival rates were found in appendicular and rectal NENs, demonstrating 10-year OS and RS of 87% and 93%, and 81% and 95%, respectively. CONCLUSIONS These long-term follow-up data demonstrate significant differences in survival for different grades, tumour stage, and primary origin of GEP-NENs, with the most favourable overall and RS rates in patients with non-metastatic grade 1 appendicular and rectal NENs. This study demonstrates unique long-term OS and RS rates using combined stratification by tumour site, grade and stage.
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21
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McGuinness MJ, Woodhouse B, Harmston C, Parker K, Kramer N, Findlay M, Print C, Merrie A, Lawrence B. Survival of patients with small bowel neuroendocrine neoplasms in Auckland, Aotearoa New Zealand. ANZ J Surg 2022; 92:1748-1753. [PMID: 35762209 PMCID: PMC9541869 DOI: 10.1111/ans.17851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 11/29/2022]
Abstract
Background Small intestinal Neuroendocrine Neoplasms (SI‐NENs) are the most common primary malignancy of the small bowel. The aim of this study is to define the survival of patients with an SI‐NEN in Auckland, Aotearoa New Zealand (AoNZ). Methods A retrospective study of all patients diagnosed with a jejunal or ileal SI‐NEN in the Auckland region between 2000 and 2012 was performed. The New Zealand NETwork! Registry was searched to identify the study cohort. Retrospective data collection was performed to collect stage, survival and follow up data. Results One hundred and seven patients were included in the study. The mean age of patients was 62.8 years (SD 11.9). The 5 and 10‐year disease‐specific survival for all patients was 66.1% (95% CI 56.5–75.7%) and 61.8% (95% CI 51.8–71.8%), respectively. Ten‐year disease‐specific survival was 100% for stage I and II, 74% (95%CI 61.7–84.4%) for stage III and 33.9% (95%CI 16.9–35.6%) for stage IV SI‐NEN. Eleven of 40 (27.5%) patients with stage III disease had recurrence and 3 of 7 (42.8%) patients with stage IV disease had recurrence. In patients with stage IV disease, neither primary resection (HR 2.25, 95% CI 0.92–5.5) nor distant resection (HR 1.72, 95% CI 0.63–4.7) were significantly associated with a disease‐specific or overall survival benefit. Conclusion This study demonstrates that stage at SI‐NEN diagnosis is associated with survival, but resection of the primary or distant metastases in patients with stage IV disease is not. There was no recurrence in patients with stage I or II disease after complete resection.
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Affiliation(s)
- Matthew J. McGuinness
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
- Whangārei Hospital, Northland District Health Board Whangārei New Zealand
| | - Braden Woodhouse
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
| | - Christopher Harmston
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
- Whangārei Hospital, Northland District Health Board Whangārei New Zealand
| | - Kate Parker
- Planning, Funding and Outcomes Waitematā District Health Board Waitakere New Zealand
| | - Nicole Kramer
- Department of Pathology North Shore Hospital, Waitematā District Health Board Waitakere New Zealand
| | - Michael Findlay
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
| | - Cristin Print
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
| | - Arend Merrie
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
- Auckland City Hospital, Auckland District Health Board Auckland New Zealand
| | - Ben Lawrence
- Faculty of Medical and Health Sciences and Maurice Wilkins Centre University of Auckland Auckland New Zealand
- Auckland City Hospital, Auckland District Health Board Auckland New Zealand
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22
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Ruggeri RM, Altieri B, Grossrubatcher E, Minotta R, Tarsitano MG, Zamponi V, MIsidori A, Faggiano A, Colao AM. Sex differences in carcinoid syndrome: A gap to be closed. Rev Endocr Metab Disord 2022; 23:659-669. [PMID: 35292889 DOI: 10.1007/s11154-022-09719-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/04/2022] [Indexed: 12/17/2022]
Abstract
The incidence of neuroendocrine neoplasms and related carcinoid syndrome (CS) has markedly increased over the last decades and women seem to be more at risk than men for developing CS. Nevertheless, very few studies have investigated sex differences in clinical presentation and outcomes of CS. However, as per other tumours, sex might be relevant in influencing tumour localization, delay in diagnosis, clinical outcomes, prognosis and overall survival in CS. The present review was aimed at evaluating sex differences in CS, as they emerge from an extensive search of the recent literature. It emerged that CS occurs more frequently in female than in male patients with NENs and women seem to have a better prognosis and a slight advantage in overall survival and response to therapy. Moreover, the disease likely impacts differently the quality of life of men and women, with different psychological and social consequences. Nevertheless, sex differences, even if partially known, are deeply underestimated in clinical practice and data from clinical trials are lacking. There is urgent need to increase our understanding of the sex-related differences of CS, in order to define tailored strategies of management of the disease, improving both the quality of life and the prognosis of affected patients.
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Affiliation(s)
- Rosaria M Ruggeri
- Department of Clinical and Experimental Medicine, Unit of Endocrinology, University of Messina, Messina, Italy.
| | - Barbara Altieri
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
| | | | - Roberto Minotta
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy
| | | | - Virginia Zamponi
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Andrea MIsidori
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
| | - Anna Maria Colao
- Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy
- Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, Italy
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23
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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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24
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Søreide JA, Kvaløy JT, Lea D, Sandvik OM, Al-Saiddi M, Haslerud TM, Garresori H, Karlsen LN, Gudlaugsson E, Søreide K. The overriding role of surgery and tumor grade for long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based cohort study. Cancer Rep (Hoboken) 2021; 5:e1462. [PMID: 34105314 PMCID: PMC8842708 DOI: 10.1002/cnr2.1462] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/26/2021] [Accepted: 05/12/2021] [Indexed: 12/13/2022] Open
Abstract
Background Gastroenteropancreatic neuroendocrine neoplasms (GEP‐NENs) comprise a heterogeneous disease group. Factors that affect long‐term survival remain uncertain. Complete population‐representative cohorts with long‐term follow‐up are scarce. Aim To evaluate factors of importance for the long‐term survival. Methods and results An Observational population‐based study on consecutive GEP‐NEN patients diagnosed from 2003 to 2013, managed according to national guidelines. Univariable and multivariable survival analyses were performed to evaluate overall survival (OS) and to identify independent prognostic factors. One hundred ninety eligible patients (males, 58.9%) (median age, 60.0 years; range, 10.0–94.2 years) were included. The small bowel, appendix, and pancreas were the most common tumor locations. The World Health Organization (WHO) tumor grade 1–3 distributions varied according to the primary location and disease stage. Primary surgery with curative intent was performed in 66% of the patients. The median OS of the study population was 183 months with 5‐ and 10‐year OS rates of 66% and 57%, respectively. Only age, WHO tumor grade, and primary surgical treatment were independent prognostic factors for OS. Conclusion The outcomes of GEP‐NEN patients are related to several factors including age and primary surgical treatment. WHO tumor grading, based on the established criteria, should be routine in clinical practice. This may improve clinical decision‐making and allow the comparison of outcomes among different centers.
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Affiliation(s)
- Jon Arne Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Jan Terje Kvaløy
- Department of Research, Stavanger University Hospital, Stavanger, Norway.,Department of Mathematics and Physics, University of Stavanger, Stavanger, Norway
| | - Dordi Lea
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Department of Pathology, Stavanger University Hospital, Stavanger, Norway
| | - Oddvar M Sandvik
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Mohammed Al-Saiddi
- Department of Radiology and Nuclear Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Torjan M Haslerud
- Department of Radiology and Nuclear Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Herish Garresori
- Department of Oncology, Stavanger University Hospital, Stavanger, Norway
| | - Lars N Karlsen
- Department of Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Einar Gudlaugsson
- Department of Pathology, Stavanger University Hospital, Stavanger, Norway
| | - Kjetil Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
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25
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Wyld D, Moore J, Tran N, Youl P. Incidence, survival and stage at diagnosis of small intestinal neuroendocrine tumours in Queensland, Australia, 2001-2015. Asia Pac J Clin Oncol 2021; 17:350-358. [PMID: 33567164 DOI: 10.1111/ajco.13503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 09/10/2020] [Indexed: 12/13/2022]
Abstract
AIM Multiple studies have observed increasing incidence of small intestinal (SI) neuroendocrine tumours (NETs). The aim of this study was to describe incidence, mortality and survival of SI NETs by sub-site and stage at diagnosis. METHODS Data on patients diagnosed with SI NETs between 2001 and 2015 were sourced from the Queensland Oncology Repository. Staging algorithms utilising several data sources were used to calculate stage at diagnosis (localised, regional or metastatic disease). RESULTS We identified 778 SI NETs and of those 716 (92%) had either a documented or derived stage. Incidence doubled from 0.68 per 100 000 to 1.42 per 100 000 over the 15-year period. Most common site was ileum (49.1%) and 84.2% were of carcinoid morphology type. Stage at diagnosis was calculated for 91.7% of patients with 28.3% presenting with regional involvement and 23.9% with distant metastasis. Risk factors associated with metastatic disease were jejunal and SI site not otherwise specified, neuroendocrine carcinoma histology and residing in a rural area. Increasing incidence of localised disease and a corresponding reduction in metastatic disease was observed over time. Five-year cause-specific survival for patients diagnosed between 2001 and 2005 was 82.5%, increasing to 93.8% from 2011 to 2015. Survival was lowest for those with metastatic disease (74.2%). Survival increased between 2001 to 2005 and 2011 to 2015 for each disease stage. CONCLUSIONS SI NET incidence in Queensland doubled between 2001 and 2015. Survival was high and improved over time.
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Affiliation(s)
- David Wyld
- Department of Medical Oncology, The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Cancer Alliance Queensland, Metro South Hospital and Health Service, Brisbane, Queensland, Australia
| | - Julie Moore
- Cancer Alliance Queensland, Metro South Hospital and Health Service, Brisbane, Queensland, Australia
| | - Nancy Tran
- Cancer Alliance Queensland, Metro South Hospital and Health Service, Brisbane, Queensland, Australia
| | - Philippa Youl
- Cancer Alliance Queensland, Metro South Hospital and Health Service, Brisbane, Queensland, Australia
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26
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Shi M, Zhou B. Clinical Characteristics and Prognostic Factors of Early-Onset Pancreatic Neuroendocrine Tumors. Cancer Control 2021; 28:1073274820986827. [PMID: 33491476 PMCID: PMC8482713 DOI: 10.1177/1073274820986827] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) has increased significantly. The purpose of this study was to analyze the clinical characteristics and prognosis of patients under 50 years old. METHODS Patients with PNETs recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 were analyzed. The clinical characteristics were analyzed by Chi-square test. The Kaplan-Meier method was used to estimate overall survival (OS). Multivariate Cox proportional risk regression analysis was used to determine independent prognostic factors. RESULTS 2,303 patients included, of which 547 (23.8%) patients were younger than 50 years old. The number of younger patients has increased steadily, while the proportion in total PNETs decreased recently. Compared with older group, the proportion of the Black, grade I/II, and surgery were higher in early-onset PNETs. Liver was the most frequent metastatic site. There was no significant difference in the incidence of different metastatic sites between younger and older PNETs patients, while younger patients had better OS (P < 0.05). Grade, N stage, M stage, and surgery were independent prognostic factors for OS in early-onset PNETs. CONCLUSIONS Younger patients have unique clinicopathological characteristics compared with older patients in PNETs. Better OS was observed in younger patients which might due to the higher proportion of well-differentiated tumor and surgery than older patients.
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Affiliation(s)
- Min Shi
- Department of Gastroenterology, Liyang People's Hospital, Liyang City, Jiangsu, China
| | - Biao Zhou
- Department of Gastroenterology, Liyang People's Hospital, Liyang City, Jiangsu, China
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27
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Palmer J, Leeuwenkamp OR. Cost-effectiveness of lutetium ( 177Lu) oxodotreotide vs everolimus in gastroenteropancreatic neuroendocrine tumors in Norway and Sweden. World J Clin Cases 2020; 8:4793-4806. [PMID: 33195647 PMCID: PMC7642527 DOI: 10.12998/wjcc.v8.i20.4793] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/21/2020] [Accepted: 09/25/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a relatively rare and heterogenous group of tumors. Currently available treatment options for patients with progressive GEP-NETs include lutetium (177Lu) oxodotreotide (177Lu-Dotatate) and everolimus [as well as sunitinib for patients with pancreatic NETs (P-NETs)].
AIM To perform a health economic analysis to determine the cost-effectiveness of 177Lu-Dotatate compared with everolimus in patients with unresectable or metastatic midgut-NETs or P-NETs in both Sweden and Norway.
METHODS Simulations were performed using a three-state partitioned survival model and analyses were performed separately for patients with midgut-NETs and P-NETs. Clinical input data were sourced from an indirect comparison that utilized survival data from clinical trials of 177Lu-Dotatate and everolimus. The analyses were performed from the healthcare payer perspective over a time horizon of 20 years. For Sweden, future costs and clinical outcomes were discounted at 3% per annum. For Norway, a discount rate of 4% per annum was applied.
RESULTS For Sweden, improved survival outcomes and higher lifetime costs with 177Lu-Dotatate resulted in an incremental cost-effectiveness ratio (ICER) of SEK 391194 per quality-adjusted life year (QALY) gained for midgut NETs and SEK 16764 per QALY gained for P-NETs for 177Lu-Dotatate compared with everolimus. For Norway, the corresponding ICERs were NOK 244444 per QALY gained and NOK 106451 per QALY gained, respectively. One-way sensitivity analyses revealed that the results were most sensitive to changes in drug acquisition costs and health state utility values.
CONCLUSION In both Sweden and Norway, from a healthcare provider perspective, 177Lu-Dotatate is likely to be considered cost-effective relative to everolimus for the treatment of patients with unresectable or metastatic, progressive midgut-NETs or P-NETs.
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Affiliation(s)
- Jayne Palmer
- Ossian Health Economics and Communications, Basel 4051, Switzerland
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28
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Survival in Patients with Neuroendocrine Tumours of the Small Intestine: Nomogram Validation and Predictors of Survival. J Clin Med 2020; 9:jcm9082502. [PMID: 32756529 PMCID: PMC7464451 DOI: 10.3390/jcm9082502] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/24/2020] [Accepted: 07/29/2020] [Indexed: 02/07/2023] Open
Abstract
Neuroendocrine tumours of the small intestine (SI-NETs) are rare and heterogeneous. There is an unmet need for prognostication of disease course and to aid treatment strategies. A previously developed nomogram based on clinical and tumour characteristics aims to predict disease-specific survival (DSS) in patients with a SI-NET. We aimed to validate the nomogram and identify predictors of survival. Four hundred patients with a grade 1 or 2 SI-NET were included, between January 2000 and June 2016. Predicted 5- and 10-year survival was compared to actual DSS. Multivariable analysis identified predictors for actual DSS. We found that in low-, medium- and high-risk groups 5-year nomogram DSS vs. actual DSS was 0.86 vs. 0.82 (p < 0.001), 0.52 vs. 0.71 (p < 0.001) and 0.26 vs. 0.53 (p < 0.001), respectively. Ten-year nomogram DSS vs. actual DSS was 0.68 vs. 0.69 (p < 0.001), 0.40 vs. 0.50 (p < 0.001) and 0.20 vs. 0.35 (p < 0.001), respectively. Age, WHO-performance score of 2, Ki-67 index ≥10, unknown primary tumour, CgA > 6x ULN and elevated liver tests were identified as independent predictors for a worse DSS. This shows that the nomogram was able to differentiate, but underestimated DSS for patients with a SI-NET. Improvement of prognostication incorporating new emerging biomarkers is necessary to adequately estimate survival.
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Begum N, Maasberg S, Pascher A, Plöckinger U, Gress TM, Wurst C, Weber F, Raffel A, Krausch M, Holzer K, Bartsch DK, Musholt TJ, Keck T, Anlauf M, Rinke A, Pape UF, Goretzki PE. Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry. Langenbecks Arch Surg 2020; 405:145-154. [PMID: 32372309 DOI: 10.1007/s00423-020-01868-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 03/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.
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Affiliation(s)
- Nehara Begum
- Department for General-, Visceral- and Minimalinvasive Surgery, Agaplesion Evangelisches Klinikum Schaumburg, Obernkirchen, Germany.
| | - Sebastian Maasberg
- Department for Internal Medicine and Gastroenterology, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charite, University Medicine Berlin, Berlin, Germany
| | - Andreas Pascher
- Department General-, Visceral- and Transplant Surgery, University Hospital Münster, Münster, Germany
| | - Ursula Plöckinger
- Centre of Metabollism: Endocrinology, Diabetes and Metabolism, Campus Virchow Clinic, Charite University-Medicine Berlin, Berlin, Germany
| | - Thomas M Gress
- Department of Gastroenterology and Endocrinology, University Hospital Marburg (UKGM), Marburg, Germany
| | - Christine Wurst
- Department of Surgery, Klinikum Crailsheim, Crailsheim, Germany
| | - Frank Weber
- Department of General-, Visceral- and Transplantation Surgery, Division of Endocrine Surgery, Medical Faculty, University Duisburg-Essen, Duisburg, Germany
| | - Andreas Raffel
- Department for General-, Visceral- and Endocrine Surgery, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
| | - Markus Krausch
- Department for General-, Visceral- and Endocrine Surgery, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Section of Endocrine Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Thomas J Musholt
- Department of General, Visceral and Transplantation Surgery, Section of Endocrine Surgery, University Medicine Mainz, Mainz, Germany
| | - Tobias Keck
- Department of General Surgery, University Hospital Schleswig-Holstein, Lübeck, Germany
| | | | - Anja Rinke
- Department of Gastroenterology and Endocrinology, University Hospital Marburg (UKGM), Marburg, Germany
| | - Ulrich-Frank Pape
- Department for Internal Medicine and Gastroenterology, Asklepios Hospital St. Georg, Lohmühlenstrasse 5, Hamburg, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charite, University Medicine Berlin, Berlin, Germany
| | - Peter E Goretzki
- Department of General, Visceral and Transplant Surgery, Section of Endocrine Surgery, Charite, University Medicine Berlin, Berlin, Germany
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Mogl MT, Dobrindt EM, Buschermöhle J, Bures C, Pratschke J, Amthauer H, Wetz C, Jann H. Influence of Gender on Therapy and Outcome of Neuroendocrine Tumors of Gastroenteropancreatic Origin: A Single-Center Analysis. Visc Med 2020; 36:20-27. [PMID: 32110653 DOI: 10.1159/000505500] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 12/17/2019] [Indexed: 12/19/2022] Open
Abstract
Introduction Gender-specific treatment is gaining growing attention in various fields of medicine. In gastrointestinal cancer, influence of sex on outcome has been discussed, while this has not been the case in neuroendocrine tumors. Overall, the incidence of neuroendocrine neoplasms is rising, especially for appendiceal neuroendocrine neoplasms in women. Also, women seem to have a slight advantage in response to therapy, especially for liver metastases. Objectives This single-center analysis aimed to investigate gender-specific differences in our cohort related to distribution, therapy, and outcome. Methods Patients from the NET registry as well as the clinic database were evaluated retrospectively concerning overall survival and response to therapy with respect to gender. A subgroup analysis was carried out for patients with low grading and response to chemotherapy, as well as for patients with good and moderate grading receiving peptide receptor radionuclide therapy and for a group of patients with liver surgery. Results No specific differences could be detected for overall survival or response to therapy between male and female patients. Mean survival was estimated with 242.2 months (±10.39 SD) altogether and 221.7 months (± 13.02 SD) for male patients and 253.5 months (±15.24 SD) for female patients from the NET registry from initial diagnosis. There was no significant difference between female and male patients (p = 0.136). For patients receiving chemotherapy, overall survival from initial diagnosis was calculated with 26 months (±2.59) and did not show any significant differences between female and male patients 24.8 months (±2.81 SD) vs. 27.8 months (±3.86 SD, p = 0.87). Patients undergoing peptide receptor radionuclide therapy showed a median progression-free survival of 26.9 months (±2.82 SD), with 16.9 (±5.595 SD) and 26.9 months (±3.019 SD) for male and female patients, respectively (p = 0.2). In the group of patients with liver surgery, female patients reached an estimated overall survival of 64.7 months (±4.16 SD), male patients 65.1 months (±2.79 SD, p = 0.562). Conclusion Our cohort did not reveal significant differences in outcome and response to therapy with regards to gender.
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Affiliation(s)
- Martina T Mogl
- Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Eva M Dobrindt
- Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Josephine Buschermöhle
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Mitte, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Claudia Bures
- Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Holger Amthauer
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Christoph Wetz
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Henning Jann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Mitte, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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Lemelin A, Maucort-Boulch D, Castel-Kremer E, Forestier J, Hervieu V, Lorcet M, Boutitie F, Theillaumas A, Robinson P, Duclos A, Lombard-Bohas C, Walter T. Elderly Patients with Metastatic Neuroendocrine Tumors Are Undertreated and Have Shorter Survival: The LyREMeNET Study. Neuroendocrinology 2020; 110:653-661. [PMID: 31586998 DOI: 10.1159/000503901] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Accepted: 10/04/2019] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The incidence of neuroendocrine tumors (NETs) is rising, especially in elderly patients. The elderly cancer population presents considerable challenges, yet little is known about the characteristics, treatment patterns, and outcomes of metastatic NET (mNET) patients. METHODS The Lyon Real-life Evidence in Metastatic NeuroEndocrine Tumors study (LyREMeNET, NCT03863106) included consecutive mNET patients, diagnosed between January 1990 and December 2017. The exclusion criteria were nonmetastatic NET, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-nonneuroendocrine neoplasms. We aimed to compare patients ≥70 years old to patients <70 years old. RESULTS A total of 866 patients were included, 198 (23%) were ≥70 years old. There was no significant difference in characteristics except that elderly patients had synchronous metastasis more frequently. Elderly patients received significantly fewer treatments (median of 2.0 vs. 3.0 lines, respectively, p < 0.0001), were significantly less frequently treated by chemotherapy (32 vs. 54%), targeted therapy (16 vs. 30%), peptide receptor radionuclide therapy (5 vs. 16%), and they underwent significantly less frequently locoregional intervention. Median overall survival was significantly shorter in elderly patients (5.2 vs. 9.6 years). The most frequent cause of death was related to disease progression (71%). Multivariate analysis found that, after adjustment for tumor location, tumor grade, and number of metastatic sites, age remained significantly associated with overall survival (HR 1.66, 95% CI 1.26-2.18), indicating a poorer survival in patients ≥70 years old in comparison with younger patients (p = 0.0003). CONCLUSION Patients ≥70 years old have a worse survival, die frequently from their disease, and are undertreated compared to younger patients.
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Affiliation(s)
- Annie Lemelin
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Delphine Maucort-Boulch
- Service de Biostatistique, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
- Lyon 1 Claude Bernard University, Lyon, France
| | - Elisabeth Castel-Kremer
- Service de Médecine Gériatrique, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Julien Forestier
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Valérie Hervieu
- Service Central d'Anatomie et Cytologie Pathologiques, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
- Lyon 1 Claude Bernard University, Lyon, France
| | - Marianne Lorcet
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Florent Boutitie
- Service de Biostatistique, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
| | - Aurélie Theillaumas
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | - Antoine Duclos
- Service des Données de Santé, Hospices Civils de Lyon, Health Services and Performance Research lab (HESPER EA 7425), Lyon, France
- Lyon 1 Claude Bernard University, Lyon, France
| | - Catherine Lombard-Bohas
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
| | - Thomas Walter
- Service de Gastroentérologie et d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France,
- Lyon 1 Claude Bernard University, Lyon, France,
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Li MX, Li QY, Xiao M, Wan DL, Chen XH, Zhou L, Xie HY, Zheng SS. Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors. Hepatobiliary Pancreat Dis Int 2019; 18:538-545. [PMID: 30981633 DOI: 10.1016/j.hbpd.2019.03.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 03/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Primary hepatic neuroendocrine neoplasms (PHNENs) are extremely rare and few articles have compared the prognosis of PHNENs with other neuroendocrine neoplasms (NENs). This study aimed to investigate the different prognosis between PHNENs and pancreatic NEN (PanNENs) and evaluate the relevant prognosis-related factors. METHODS From January 2012 to October 2016, a total of 44 NENs patients were enrolled and divided into two groups according to the primary tumor location which were named group PHNENs (liver; n = 12) and group PanNENs (pancreas; n = 32). Demographic, clinical characteristics and survival data were compared between the two groups with Kaplan-Meier method and log-rank tests. Prognostic factors were analyzed using the Cox regression model. RESULTS The overall survival of group PHNENs and group PanNENs were 25.4 ± 6.7 months and 39.8 ± 3.7 months, respectively (P = 0.037). The cumulative survival of group PanNENs was significantly higher than that of group PHNENs (P = 0.029). Univariate analysis revealed that sex, albumin, total bilirubin, total bile acid, aspartate aminotransferase, alkaline phosphatase, α-fetoprotein and carbohydrate antigen 19-9, histological types, treatments and primary tumor site were the prognostic factors. Further multivariate analysis indicated that albumin (P = 0.008), histological types NEC (P = 0.035) and treatments (P = 0.005) were the independent prognostic factors. Based on the histological types, the cumulative survival of patients with well-differentiated neuroendocrine tumor was significant higher than that of patients with poorly differentiated neuroendocrine carcinoma in group PHNENs (P = 0.022), but not in group PanNENs (P > 0.05). According to the different treatments, patients who received surgery had significantly higher cumulative survival than those with conservative treatment in both groups (P < 0.05). CONCLUSIONS PHNENs have lower survival compared to PanNENs. Histological types and treatments affect the prognosis. Surgical resection still remains the first line of treatment for resectable lesions and can significantly improve the survival.
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Affiliation(s)
- Meng-Xia Li
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qi-Yong Li
- Division of Hepatobiliary Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310004, China
| | - Min Xiao
- Division of Hepatobiliary Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310004, China
| | - Da-Long Wan
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xin-Hua Chen
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lin Zhou
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hai-Yang Xie
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shu-Sen Zheng
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Altieri B, Di Dato C, Martini C, Sciammarella C, Di Sarno A, Colao A, Faggiano A. Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management. Cancers (Basel) 2019; 11:cancers11091332. [PMID: 31500357 PMCID: PMC6770134 DOI: 10.3390/cancers11091332] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 08/28/2019] [Accepted: 09/05/2019] [Indexed: 12/20/2022] Open
Abstract
Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient’s quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.
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Affiliation(s)
- Barbara Altieri
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, 97080 Wuerzburg, Germany.
| | - Carla Di Dato
- Department of Clinical Medicine, Bufalini Hospital, 47521 Cesena, Italy.
| | - Chiara Martini
- Clinica Medica 3, Department of Medicine, DIMED, University of Padova, 35128 Padova, Italy.
| | - Concetta Sciammarella
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37126 Verona, Italy.
| | | | - Annamaria Colao
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.
| | - Antongiulio Faggiano
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
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Naraev BG, Halland M, Halperin DM, Purvis AJ, O'Dorisio TM, Halfdanarson TR. Management of Diarrhea in Patients With Carcinoid Syndrome. Pancreas 2019; 48:961-972. [PMID: 31425482 PMCID: PMC6867674 DOI: 10.1097/mpa.0000000000001384] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 07/10/2019] [Indexed: 02/06/2023]
Abstract
Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.
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Affiliation(s)
| | - Magnus Halland
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Daniel M. Halperin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Amy J. Purvis
- University of Arizona Cancer Center (UACC), Phoenix, AZ
| | - Thomas M. O'Dorisio
- Neuroendocrine Cancer Program, University of Iowa Health Care, Iowa City, IA
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Calanchini M, Tadman M, Krogh J, Fabbri A, Grossman A, Shine B. Measurement of urinary 5-HIAA: correlation between spot versus 24-h urine collection. Endocr Connect 2019; 8:1082-1088. [PMID: 31265996 PMCID: PMC6652243 DOI: 10.1530/ec-19-0269] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 07/01/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND The 24-h urinary output of 5-hydroxyindoleacetic acid (5-HIAA) is used to monitor disease progression and treatment responses of neuroendocrine neoplasms (NENs). Several conditions are required for 5-HIAA assay, involving urine collection/preservation and food/drug restrictions. AIM To evaluate the correlation between 5-HIAA concentration in a spot urine sample and the output in a 24-h urine collection, and whether spot urine specimens can replace 24-h collection. METHODS Patients with NENs or symptoms suggestive of NENs were asked to provide a separate spot urine at the end of the 24-h urine collection for 5-HIAA assessment. The upper reference limit for 24-h urinary 5-HIAA was 40 µmol/24 h. 5-HIAA measurements in spot urine samples were corrected for variation in urine flow rate by expressing results as a ratio to creatinine concentration. RESULTS We included 136 paired urinary samples for 5-HIAA assessment from 111 patients (100 NENs). The correlation between 5-HIAA values measured in 24-h and spot urines was r = +0.863 (P < 0.001) and r = +0.840 (P < 0.001) including only NEN patients. Using the 24-h urinary 5-HIAA as reference method, the AUC on ROC analysis for spot urinary 5-HIAA was 0.948 (95% CI, 0.914-0.983; P < 0.001), attaining a sensitivity of 83% and specificity of 95% using 5.3 mol/mmol as cut-off for the spot urine. The AUC among NEN patients alone was 0.945 (95% CI, 0.904-0.987; P < 0.001). CONCLUSIONS The ratio of 5-HIAA to creatinine in a spot urine could replace the measurement of 5-HIAA output in a 24-h urine collection, especially for follow-up of patients with known elevated 5-HIAA levels.
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Affiliation(s)
- Matilde Calanchini
- Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
- Endocrinology & Metabolism Unit, CTO A. Alesini Hospital ASL Roma 2, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
- Correspondence should be addressed to M Calanchini:
| | - Michael Tadman
- Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Jesper Krogh
- Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Andrea Fabbri
- Endocrinology & Metabolism Unit, CTO A. Alesini Hospital ASL Roma 2, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Ashley Grossman
- Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
| | - Brian Shine
- Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, University of Oxford, Oxford, UK
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Kooyker AI, Verbeek WH, van den Berg JG, Tesselaar ME, van Leerdam ME. Change in incidence, characteristics and management of colorectal neuroendocrine tumours in the Netherlands in the last decade. United European Gastroenterol J 2019; 8:59-67. [PMID: 32213058 PMCID: PMC7006007 DOI: 10.1177/2050640619865113] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are rare. However, a rising incidence has been reported over the past decades. For colorectal NETs, this is presumably caused by an increased awareness of colorectal diseases and colonoscopic procedures. This study aims to analyse the change in incidence of colorectal NETs, characteristics and management and evaluate the proportion of colorectal NETs detected in a national colorectal cancer (CRC) screening programme. METHODS Histopathological reports on colorectal well-differentiated NETs detected between 2006 and 2016 were collected from the Dutch pathology database (PALGA) containing nationwide histo- and cytopathology reports of all pathology laboratories in the Netherlands. RESULTS Colorectal NETs were detected in 1055 individuals. Increasing incidence rates were observed from 0.36 per 100,000 inhabitants in 2006 to 0.75 per 100,000 inhabitants in 2011 (p value < 0.001), remaining stable afterward. Most NETs were grade I (73.5%) and detected in the rectum (76.4%). The majority (88.2%) were detected by colonoscopy, and the final intervention depended significantly on primary location of the tumour; 94.6% of rectal NETs were endoscopically removed, whereas 61.0% of colonic NETs were removed by surgery. There was an increase in local excision both of rectal and colonic NETs over the years instead of radical resection. Screening for CRC started in 2014 and contributed by detecting 32% of the diagnosed colorectal NETs within the invited age group, of which 94.6% were detected at an early stage. CONCLUSION The incidence of reported colorectal NETs in the Netherlands doubled over the last decade. The Dutch CRC screening programme had a clear contribution to colorectal NETs incidence among its target population. A shift to more local management of detected lesions was observed over time.
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Affiliation(s)
- Arthur I Kooyker
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Wieke Hm Verbeek
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - José G van den Berg
- Department of Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Margot Et Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Monique E van Leerdam
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands
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Póvoa S, Azevedo D, Marques C, Barroca H, Costa A. Unknown primary large-cell neuroendocrine tumor. AUTOPSY AND CASE REPORTS 2018; 8:e2018025. [PMID: 30533401 PMCID: PMC6145498 DOI: 10.4322/acr.2018.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 05/23/2018] [Indexed: 12/25/2022] Open
Abstract
Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare
incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal
tract, although they are potentially ubiquitous throughout the body. Primary unknown NET
has a worse prognosis and shorter survival comparing with other NETs, with limited available
data in the literature concerning this subgroup. The authors report the case of large-cell
NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged
adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant
neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high
mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical
study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid
transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two
infracentimetric lung lesions that could not be accessed for biopsy and were negative at both
somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed
with three mediastinal masses, so the patient was started on chemotherapy with carboplatin
and etoposide with initial total response. Early progression showed no response to further
chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated
with local radiotherapy. This patient has an atypical long survival (54 months) compared
to the literature data. In fact, there are few long-term survivors of large-cell NET and they
are all related to complete surgical resection.
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Affiliation(s)
- Sara Póvoa
- a Centro Hospitalar de São João, Medical Oncology Department. Porto, Portugal.,b Centro Hospitalar de São João, Pathology Department. Porto, Portugal
| | - Daniela Azevedo
- a Centro Hospitalar de São João, Medical Oncology Department. Porto, Portugal.,b Centro Hospitalar de São João, Pathology Department. Porto, Portugal
| | - Cristiana Marques
- a Centro Hospitalar de São João, Medical Oncology Department. Porto, Portugal.,b Centro Hospitalar de São João, Pathology Department. Porto, Portugal
| | - Helena Barroca
- a Centro Hospitalar de São João, Medical Oncology Department. Porto, Portugal.,b Centro Hospitalar de São João, Pathology Department. Porto, Portugal
| | - Andreia Costa
- a Centro Hospitalar de São João, Medical Oncology Department. Porto, Portugal.,b Centro Hospitalar de São João, Pathology Department. Porto, Portugal
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Bongiovanni A, Recine F, Foca F, Fausti V, Riva N, Fabbri G, Severi S, Liverani C, De Vita A, Spadazzi C, Miserocchi G, Mercatali L, Amadori D, Ibrahim T. Metastatic neuroendocrine neoplasia treatments in patients over 70 years of age. Endocr Connect 2018; 7:1535-1541. [PMID: 30530877 PMCID: PMC6311458 DOI: 10.1530/ec-18-0478] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 12/07/2018] [Indexed: 01/26/2023]
Abstract
The incidence of neuroendocrine neoplasia (NEN) is higher in individuals ≥70 years of age (elderly) who are underrepresented in clinical trials because of comorbidities and low performance status. We retrospectively analyzed the outcome of elderly patients with metastatic NEN (mNEN). Comorbidities were summarized by Charlson Comorbidity Index (CCI), Kaplan-Meier method was applied to estimate overall survival (OS) and Cox's proportional hazard model was used to assess the impact of known prognostic factors. We retrieved data on 145 mNEN patients aged ≥70 years seen at our center from June 2007 to March 2016. Fifty-six (38.6%) were aged ≥75 years. ECOG PS was 0 in 45.7% of cases and CCI was 0 in 41.0% and 1 in 37.4%. A total of 75.4% of patients had grade (G)1/G2 NEN and 24.6%, G3. Octreoscan/Gallium PET/CT and FDG-PET/CT were positive in 94.2% and 70.3% of cases, respectively. Median follow-up was 72.3 (53.2-85.1) months. Seventy-nine patients received first-line somatostatin analogs (SSA), 23 peptide receptor radionuclide therapy (PRRT) and 36 chemotherapy (CHT). Seven did not undergo first-line therapy and 102 received more than one line. Median overall survival (mOS) was 5.1 years (95% CI: 3.4-6.6). No differences in mOS were seen according to CCI. First-line PRRT patients had a mOS of 6.5 years (95% CI: 3.3-not reached (NR)), SSA 5.7 years (95% CI: 4.2-7) and CHT 5.9 years (95% CI: 0.4-NR). mOS in CHT-treated G3 patients was 1.5 years (1.0-2.5). ECOG PS and FDG PET/CT were identified as independent prognostic factors. Results suggest that the above treatments positively impacted OS in elderly mNEN patients, including those aged ≥75 years.
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Affiliation(s)
- Alberto Bongiovanni
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
- Correspondence should be addressed to A Bongiovanni:
| | - Federica Recine
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Flavia Foca
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Valentina Fausti
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Nada Riva
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Greta Fabbri
- Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Stefano Severi
- Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Chiara Liverani
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alessandro De Vita
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Chiara Spadazzi
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giacomo Miserocchi
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Laura Mercatali
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Dino Amadori
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Toni Ibrahim
- Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
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Man D, Wu J, Shen Z, Zhu X. Prognosis of patients with neuroendocrine tumor: a SEER database analysis. Cancer Manag Res 2018; 10:5629-5638. [PMID: 30519109 PMCID: PMC6239108 DOI: 10.2147/cmar.s174907] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Neuroendocrine tumors (NETs) are a group of heterogeneous cancers arising from a variety of anatomic sites. Their incidence has increased in recent years. This study aimed to analyze the prognosis of NETs originating from different anatomic sites. Methods We identified 73,782 patients diagnosed with NETs from the Surveillance Epidemiology and Ends Results (SEER) database from 1973 to 2014. Clinical data were compared between patients with different primary tumor sites using the chi-squared test. Differences in survival among NET patients with different tumor sites were compared by Kaplan–Meier analysis. Cox proportional hazard models were performed to identify the prognostic factors of overall survival. Results In this cohort, the lung/bronchus was the most common site of NETs, accounting for 30.6%, followed by the small intestine (22.2%), rectum (16.2%), colon (13.4%), pancreas (10.8%), and stomach (6.8%). Totally, 73,782 patients were selected for this cohort from 1973 to 2014. The median survival duration was 41 months. The 1-, 3-, 5-, and 10-year overall survival rates for patients with NETs were 72.8%, 52.7%, 39.4%, and 18.1%, respectively. Patients with NETs located in the rectum had the best prognosis, followed by those with NETs in the small intestine (HR, 1.660, 95% CI, 1.579, 1.744), lung/bronchus (HR, 1.786, 95% CI, 1.703, 1.874), stomach (HR, 1.865, 95% CI, 1.755, 1.982), and colon (HR, 1.896, 95% CI, 1.799, 1.999). Patients with NETs in the pancreas had the highest risk of mortality (HR, 2.034, 95% CI, 1.925, 2.148). Conclusion Significant differences in survival were found among various primary tumor sites. NETs in the rectum had the best prognosis, while those in the pancreas had the worst. Primary tumor sites might be one of the most useful outcome predictors in patients with NETs.
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Affiliation(s)
- Da Man
- Department of Colorectal Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China,
| | - Jingjing Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
| | - Zhan Shen
- Department of Colorectal Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China,
| | - Xiaoyi Zhu
- Department of Colorectal Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China,
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