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1
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Luo W, Chen H, Zhang T. Impact of Combined Chemotherapy and Targeted Therapy on Pancreatic Neuroendocrine Carcinoma with Liver Metastasis: A Single-Center Modified Nomogram Analysis. Onco Targets Ther 2024; 17:509-519. [PMID: 38933411 PMCID: PMC11204791 DOI: 10.2147/ott.s466213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024] Open
Abstract
Objective To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients. Methods A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model's feasibility, accuracy, and reliability. Results Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping. Conclusion Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.
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Affiliation(s)
- Wenhao Luo
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Hao Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China
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Giri S, Sahoo J. Advancements in medical treatment for pancreatic neuroendocrine tumors: A beacon of hope. World J Gastroenterol 2024; 30:1670-1675. [PMID: 38617746 PMCID: PMC11008371 DOI: 10.3748/wjg.v30.i12.1670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/29/2024] [Accepted: 03/07/2024] [Indexed: 03/28/2024] Open
Abstract
This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors (pan-NETs), emphasizing tailored approaches for specific subtypes. Cytoreductive surgery and somatostatin analogs (SSAs) play pivotal roles in managing tumors, while palliative options such as molecular targeted therapy, peptide receptor radionuclide therapy, and chemotherapy are reserved for SSA-refractory patients. Gastrinomas, insulinomas, glucagonomas, carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies. Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research. This review underscores the evolving landscape of pan-NET treatment, offering renewed hope and improved outcomes for patients facing this complex disease.
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Affiliation(s)
- Somdatta Giri
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India
| | - Jayaprakash Sahoo
- Department of Endocrinology and Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India
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Beyer GV, Hueser S, Li R, Manika D, Lee M, Chan CHF, Howe JR, Ear PH. Gastroenteropancreatic neuroendocrine carcinoma tumor spheroid drug screen reveals vulnerability to tyrosyl-DNA phosphodiesterase 1 inhibitors. Surgery 2024; 175:605-612. [PMID: 37914572 PMCID: PMC10872605 DOI: 10.1016/j.surg.2023.08.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 07/26/2023] [Accepted: 08/08/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine carcinomas are rare neoplasms with no effective treatments and poor prognosis. Few reliable preclinical models exist for the study of gastroenteropancreatic neuroendocrine carcinomas, limiting investigation of novel treatments. We used tumor spheroids from our recently established gastroenteropancreatic neuroendocrine carcinoma patient-derived xenograft models to systematically screen for compounds with diverse structures to identify potential new categories of therapeutic agents that can target gastroenteropancreatic neuroendocrine carcinomas. METHODS Tumor spheroids were derived from our NEC913 and NEC1452 gastroenteropancreatic neuroendocrine carcinoma patient-derived xenograft models. Gastroenteropancreatic neuroendocrine carcinoma spheroids were screened against a library of 885 compounds from the National Cancer Institute Diversity Set VII collection. Cell viability was measured via AlamarBlue assay. After identification of potential therapeutic compounds, synergy screening of a selected group with temozolomide and doxorubicin was performed, and these combinations were further analyzed for γH2AX and phosphorylated-ERK proteins. RESULTS We identified 16 compounds that inhibit over 75% of gastroenteropancreatic neuroendocrine carcinoma spheroid survival. Seven are inhibitors of tyrosyl-DNA phosphodiesterase 1, a DNA repair enzyme working closely with the topoisomerase I complex. When combined with temozolomide or doxorubicin, the tyrosyl-DNA phosphodiesterase 1 inhibitor cytarabine increased the cytotoxic effects of these drugs on NEC1452 cells which was further evidenced by increasing γH2AX and decreasing phosphorylated-ERK in combination treatment compared to temozolomide alone. CONCLUSION Both NEC913 and NEC1452 gastroenteropancreatic neuroendocrine carcinoma spheroid lines are useful preclinical models for drug testing. Our library screen revealed these gastroenteropancreatic neuroendocrine carcinoma spheroids are highly sensitive to a novel class of anti-cancer drugs that target nuclear genome stability.
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Affiliation(s)
- Gabriella V Beyer
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Sophia Hueser
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Rachel Li
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Deeraj Manika
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Minhyuk Lee
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Carlos H F Chan
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA
| | - James R Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA
| | - Po Hien Ear
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA.
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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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5
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Pan WX, Zhang XM, Hao SL, Han W. Progress in immunotherapy for neuroendocrine neoplasm of the digestive system. World J Gastroenterol 2023; 29:4174-4185. [PMID: 37475845 PMCID: PMC10354576 DOI: 10.3748/wjg.v29.i26.4174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 05/29/2023] [Accepted: 06/13/2023] [Indexed: 07/10/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare heterogeneous tumors that can develop in almost any organ, with the digestive organs, including the gastrointestinal tract and pancreas being the most commonly affected sites. Despite the fact that advances in initial therapies have progressed, there is presently no recognized effective treatment for advanced NEN. Immune checkpoint inhibitors (ICIs) have shown superior efficacy in treating several types of solid tumors. Despite their successful role in the treatment of partial NENs, such as small cell lung cancer, and Merkel cell carcinoma, the role of ICIs in most of the NENs remains limited. Nevertheless, due to their specific anti-tumor mechanisms and acceptable safety profile, ICIs are a promising avenue for further study in NENs therapy. Recent clinical trials have illustrated that combination therapy with ICI is more efficient than monotherapy, and multiple clinical trials are constantly ongoing to evaluate the efficacy and safety of these combination therapies. Therefore, the purpose of this review is to provide a comprehensive summary of the clinical progress of immunotherapy in NENs affecting the digestive system, with a specific emphasis on the application of programmed cell death protein 1/programmed death receptor ligand 1 inhibitor. Furthermore, this review has an exploration of the potential beneficiary population and the inherent value of utilizing immunotherapy in the management of NENs.
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Affiliation(s)
- Wei-Xuan Pan
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
| | - Xin-Mu Zhang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Shao-Long Hao
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
| | - Wei Han
- Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China
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6
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Riechelmann RP, Taboada RG, de Jesus VHF, Iglesia M, Trikalinos NA. Therapy Sequencing in Patients With Advanced Neuroendocrine Neoplasms. Am Soc Clin Oncol Educ Book 2023; 43:e389278. [PMID: 37257140 DOI: 10.1200/edbk_389278] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Neuroendocrine neoplasms (NENs) comprise a beautifully complicated, exciting landscape of histologies and clinical behaviors. However, the nuanced complexity of low- and high-grade variants can easily overwhelm both patients and providers. In this chapter, we review the ever-expanding literature on both functioning and nonfunctioning small bowel and pancreatic NENs, touching on somatostatin analogs, hepatic-directed therapies, small molecules, radiopharmaceuticals, immunotherapy, cytotoxic chemotherapy, and new promising agents. Furthermore, we suggest some strategies to address the most challenging scenarios seen in clinical practice, including sequencing of agents, treatment of carcinoid syndrome, and options for well-differentiated high-grade disease.
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Affiliation(s)
| | - Rodrigo G Taboada
- Department of Clinical Oncology, A.C.Camargo Cancer Center, Sao Paulo, Brazil
| | | | - Michael Iglesia
- Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO
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7
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Kong G, Boehm E, Prall O, Murray WK, Tothill RW, Michael M. Integrating Functional Imaging and Molecular Profiling for Optimal Treatment Selection in Neuroendocrine Neoplasms (NEN). Curr Oncol Rep 2023; 25:465-478. [PMID: 36826704 PMCID: PMC10110720 DOI: 10.1007/s11912-023-01381-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2023] [Indexed: 02/25/2023]
Abstract
PURPOSE OF REVIEW Gastroenteropancreatic NEN (GEP-NEN) are group of malignancies with significant clinical, anatomical and molecular heterogeneity. High-grade GEP-NEN in particular present unique management challenges. RECENT FINDINGS In the current era, multidisciplinary management with access to a combination of functional imaging and targeted molecular profiling can provide important disease characterisation, guide individualised management and improve patient outcome. Multiple treatment options are now available, and combination and novel therapies are being explored in clinical trials. Precision medicine is highly relevant for a heterogenous disease like NEN. The integration of dual-tracer functional PET/CT imaging, molecular histopathology and genomic data has the potential to be used to gain a more comprehensive understanding of an individual patient's disease biology for precision diagnosis, prognostication and optimal treatment allocation.
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Affiliation(s)
- Grace Kong
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia. .,The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.
| | - Emma Boehm
- Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.,Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia
| | - Owen Prall
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - William K Murray
- Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Richard W Tothill
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.,Centre for Cancer Research and Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia
| | - Michael Michael
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.,Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
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Arrivi G, Verrico M, Roberto M, Barchiesi G, Faggiano A, Marchetti P, Mazzuca F, Tomao S. Capecitabine and Temozolomide (CAPTEM) in Advanced Neuroendocrine Neoplasms (NENs): A Systematic Review and Pooled Analysis. Cancer Manag Res 2022; 14:3507-3523. [PMID: 36575665 PMCID: PMC9790144 DOI: 10.2147/cmar.s372776] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/09/2022] [Indexed: 12/24/2022] Open
Abstract
Background Retrospective studies and single center experiences suggest a role of capecitabine combined with temozolomide (CAPTEM) in neuroendocrine tumors (NENs). Methods We performed a systematic review to assess the efficacy and safety of CAPTEM in patients affected with NENs, with the aim to better clarify the role of this regimen in the therapeutic algorithm of NENs. Results A total of 42 articles and 1818 patients were included in our review. The overall disease control rate was 77% (range 43.5%-100%). The median progression free survival ranged from 4 to 38.5 months, while the median overall survival ranged from 8 to 103 months. Safety analysis showed an occurrence of G3-G4 toxicities in 16.4% of the entire population. The most common toxicities were hematological (27.2%), gastrointestinal (8.3%,) and cutaneous (3.2%). Conclusion This systematic review demonstrated that CAPTEM was an effective and relatively safe treatment for patients with advanced well-moderate differentiated NENs of gastroenteropancreatic, lung and unknown origin.
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Affiliation(s)
- Giulia Arrivi
- Department of Clinical and Molecular Medicine, Oncology Unit, Sant’ Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Monica Verrico
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Michela Roberto
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Giacomo Barchiesi
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Antongiulio Faggiano
- Department of Clinical and Molecular Medicine, Endocrinology Unit, Sant ‘Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Paolo Marchetti
- Department of Clinical and Molecular Medicine, Oncology Unit, Sant’ Andrea University Hospital, Sapienza University of Rome, Rome, Italy
- Istituto Dermopatico dell’Immacolata (IDI-IRCCS), Rome, Italy
| | - Federica Mazzuca
- Department of Clinical and Molecular Medicine, Oncology Unit, Sant’ Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Silverio Tomao
- Department of Radiological, Oncological and Anatomo-Pathological Sciences, Medical Oncology Unit A, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
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Douangprachanh S, Joo HJ, Park HM, Han N, Jang HY, Koh YH, Kim TH, Han SS, Park SJ, Lee WJ, Woo SM, Chun JW. Capecitabine and temozolomide for metastatic intermediate to high-grade pancreatic neuroendocrine neoplasm: a single center experience. Korean J Intern Med 2022; 37:1216-1222. [PMID: 36375489 PMCID: PMC9666252 DOI: 10.3904/kjim.2022.100] [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: 03/15/2022] [Accepted: 07/14/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND/AIMS The combination of capecitabine and temozolomide (CAPTEM) is one of the treatment options for metastatic pancreatic neuroendocrine neoplasms (pNENs). This study aims to evaluate the efficacy of CAPTEM in patients with metastatic intermediate to high-grade pancreatic neuroendocrine tumor (pNET) or carcinoma (pNEC). METHODS This study was conducted retrospectively in a single center. Patients were treated for intermediate to high-grade tumor with 750 mg/m² of capecitabine twice daily from day 1 to 14 and 200 mg/m² of temozolomide once daily from day 10 to 14, repeating twice in a cycle of 28 days. The primary outcomes were durations of overall survival (OS) and progression-free survival (PFS). The secondary outcomes consisted of objective response rate and disease control rate. RESULTS A total of 12 patients (grade 2 NET in six, grade 3 NET in three, NEC in three patients) who received CAPTEM were included in this study. Patients received a median of five cycles (range, 2 to 46) of CAPTEM. The median dose combined 1,150 mg of capecitabine and 300 mg of temozolomide. The median OS and PFS were 41.2 months (range, 3.2 to 167) and 39.7 months (range, 2.1 to 100), respectively. Patients with NET had longer OS and PFS compared to those of patients with NEC (p = 0.002 and p = 0.028). High Ki-67 proliferative index (> 50%) was significantly associated with poor survival outcomes. CONCLUSION CAPTEM showed favorable survival outcomes in patients with metastatic intermediate to high-grade pNENs. Our study supports that CAPTEM may be an effective treatment option for metastatic pNENs.
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Affiliation(s)
- Sathathone Douangprachanh
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
- Cancer Center, Mittaphab Hospital, Vientiane, Laos
| | - Hyun Jin Joo
- Division of Gastroenterology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul,
Korea
| | - Hyeong Min Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Nayoung Han
- Department of Pathology, National Cancer Center, Goyang,
Korea
| | - Hye Young Jang
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Young Hwan Koh
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Tae Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Sung-Sik Han
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Woo Jin Lee
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
| | - Jung Won Chun
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang,
Korea
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Raderer M, Kiesewetter B. The NET G3 enigma: dealing with a “new” entity. MEMO - MAGAZINE OF EUROPEAN MEDICAL ONCOLOGY 2022. [DOI: 10.1007/s12254-022-00848-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
SummaryNeuroendocrine neoplasms of the gastroenteropancreatic system (GEP-NENs) have historically been graded into well-differentiated neuroendocrine tumors (NETs) G 1 and 2 and undifferentiated neuroendocrine carcinomas (NEC) G3 according to the proliferative index Ki-67, with the latter being larger than 20% for G3 NENs. However, clinical and pathological findings have suggested G3 NENs to be heterogeneous, and the most recent World Health Organization (WHO) classification has further subdivided G3 NENs into NET G3 with differentiated features and a usually lower Ki-67 (20–55%) as opposed to undifferentiated NECs. Currently, however, no standard approach to patients with NET G3 has been defined. As opposed to NET G1/G2, application of somatostatin analogues is not recommended, and the response to platinum-based chemotherapy is inferior when compared to NEC. The objective of this short review is to summarize pathological characteristics as well as therapeutic data obtained in patients with NET G3.
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Well-Differentiated Grade 3 Neuroendocrine Tumors: Characteristics, Treatments, and Outcomes From a Population-Based Study. Pancreas 2022; 51:756-762. [PMID: 36395400 PMCID: PMC9722384 DOI: 10.1097/mpa.0000000000002100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVES We evaluated a population-based cohort of metastatic well-differentiated grade 3 gastroenteropancreatic neuroendocrine tumors (G3 NETs) to describe their characteristics, prognosis, and treatment outcomes. METHODS The British Columbia provincial database was queried for G3 NETs diagnosed 2004 to 2021, and charts were reviewed to describe clinical features and outcomes. RESULTS Forty-one patients were identified, most were diagnosed with pancreatic (58.5%) or midgut (26.8%) primary tumor and Ki-67 was less than 55% in 68.3%. The primary was resected in 19 (46.3%) with median disease-free survival of 25.2 months. Once metastatic, patients received a median of one line of systemic therapy. Median overall survival with metastatic disease was 33.8 months. Median progression-free survival was longest in patients treated with capecitabine-temozolomide (20.6 months) or somatostatin analogs (7.9 months), while etoposide-platinum provided little benefit (2.4 months). Limited data of efficacy for targeted therapies and radionuclide therapy was available. Seven patients (17.1%) were also treated with local therapies, which were associated with improved overall survival (median not reached, hazard ratio, 0.23; P = 0.012). CONCLUSIONS Capecitabine-temozolomide and somatostatin analogs were associated with clinically meaningful benefit, and use of local therapies provided benefits in selected patients. Multidisciplinary discussion is essential to optimize individual outcomes in this heterogeneous population.
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12
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Dogan I, Tastekin D, Karabulut S, Sakar B. Capecitabine and temozolomide (CAPTEM) is effective in metastatic well-differentiated gastrointestinal neuroendocrine tumors. J Dig Dis 2022; 23:493-499. [PMID: 36081250 DOI: 10.1111/1751-2980.13123] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 08/10/2022] [Accepted: 08/14/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the outcomes and prognostic factors of patients with metastatic gastrointestinal neuroendocrine tumor (mGI-NET) who were treated with capecitabine and temozolomide (CAPTEM) and somatostatin receptor ligand (octreotide or lanreotide). METHODS Clinicopathological characteristics and treatment outcomes of 43 patients with mGI-NET were retrospectively evaluated. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier curve. Cox-regression analysis was used to assess prognostic variables. RESULTS There were 23 (53.5%) men and 20 women (46.5%) with a median age of 59 years (range 27-85 y). Patients were given octreotide (86.0%) or lanreotide (14.0%) with CAPTEM. In patients with well-differentiated mGI-NET, median PFS was 17.4 months, and the disease control rate was 71.1%. Patients with poorly differentiated mGI-NET showed no response, and the median PFS was 4.5 months. Four (9.3%) discontinued the medication due to toxicity. Anemia (37.2%), thrombocytopenia (25.6%), and fatigue (16.3%) were the most prevalent adverse events. The 5-year OS rate was 61.0% in all patients during a median follow-up of 33.8 months. In multivariate analysis, age (P = 0.014) and tumor differentiation (P < 0.001) were statistically significant factors for OS. CONCLUSIONS CAPTEM plus somatostatin receptor ligands were efficacious and well tolerated in individuals with well-differentiated mGI-NET. However, it was ineffective for those with poorly differentiated tumors. Age of 60 years or elder and poorly differentiated tumors were related to a poor patient prognosis.
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Affiliation(s)
- Izzet Dogan
- Istanbul University Institute of Oncology, Medical Oncology, Istanbul, Turkey
| | - Didem Tastekin
- Istanbul University Institute of Oncology, Medical Oncology, Istanbul, Turkey
| | - Senem Karabulut
- Istanbul University Institute of Oncology, Medical Oncology, Istanbul, Turkey
| | - Burak Sakar
- Istanbul University Institute of Oncology, Medical Oncology, Istanbul, Turkey
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Luecke S, Fottner C, Lahner H, Jann H, Zolnowski D, Quietzsch D, Grabowski P, Cremer B, Maasberg S, Pape UF, Mueller HH, Gress TM, Rinke A, the members of the German NET Registry. Treatment Approaches and Outcome of Patients with Neuroendocrine Neoplasia Grade 3 in German Real-World Clinical Practice. Cancers (Basel) 2022; 14:2718. [PMID: 35681701 PMCID: PMC9179270 DOI: 10.3390/cancers14112718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/20/2022] [Accepted: 05/25/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Neuroendocrine neoplasia grade 3 (NEN G3) represents a rare and heterogeneous cancer type with a poor prognosis. The aim of our study was to analyze real-world data from the German NET Registry with a focus on therapeutic and prognostic aspects. METHODS NEN G3 patients were identified within the German NET Registry. Demographic data and data on treatments and outcomes were retrieved. Univariate analyses were performed using the Kaplan-Meier-method. Multivariate analysis was performed using a Cox proportional hazard model. RESULTS Of 445 included patients, 318 (71.5%) were diagnosed at stage IV. Well-differentiated morphology (NET G3) was described in 31.7%, 60% of cases were classified as neuroendocrine carcinoma (NEC), and the median Ki67 value was 50%. First-line treatment comprised chemotherapy in 43.8%, with differences in the choice of regimen with regard to NET or NEC, and surgery in 41.6% of patients. Median overall survival for the entire cohort was 31 months. Stage, performance status and Ki67 were significant prognostic factors in multivariate analysis. CONCLUSIONS The survival data of our national registry compare favorably to population-based data, probably mainly because of a relatively low median Ki67 of 50%. Nevertheless, the best first- and second-line approaches for specific subgroups remain unclear, and an international effort to fill these gaps is needed.
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Affiliation(s)
- Simone Luecke
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
| | - Christian Fottner
- Department of Internal Medicine I, Endocrinology, University Hospital Mainz, 55131 Mainz, Germany;
| | - Harald Lahner
- Department of Endocrinology and Metabolism, University Hospital of Essen, 45147 Essen, Germany;
| | - Henning Jann
- Department of Gastroenterology and Hepatology, Campus Virchow Klinikum, University Medicine Charité, 10117 Berlin, Germany;
| | | | - Detlef Quietzsch
- Praxis Dr. med. habil. Diener, 09376 Oelsnitz/Erzgebirge, Germany;
| | - Patricia Grabowski
- Klinikum Havelhöhe, Campus Virchow Klinikum, Institute of Medical Immunology, MVZ Oncology, University Medicine Charité, 10117 Berlin, Germany;
| | - Birgit Cremer
- Department of Oncology, University Hospital of Cologne, 50923 Cologne, Germany;
| | - Sebastian Maasberg
- Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, Germany; (S.M.); (U.-F.P.)
| | - Ulrich-Frank Pape
- Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, 20099 Hamburg, Germany; (S.M.); (U.-F.P.)
| | - Hans-Helge Mueller
- Institute of Medical Biometry and Epidemiology, Philipps University Marburg, 35037 Marburg, Germany;
| | - Thomas Matthias Gress
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
| | - Anja Rinke
- UKGM Marburg, Department of Gastroenterology, Philipps University Marburg, 35037 Marburg, Germany; (S.L.); (T.M.G.)
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Li YL, Cheng ZX, Yu FH, Tian C, Tan HY. Advances in medical treatment for pancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:2163-2175. [PMID: 35721885 PMCID: PMC9157622 DOI: 10.3748/wjg.v28.i20.2163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/31/2021] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms with strong heterogeneity that have experienced an increasing incidence rate in recent years. For patients with locally advanced or distant metastatic PanNENs, systemic treatment options vary due to the different differentiations, grades and stages. The available options for systemic therapy include somatostatin analogs, mole-cularly targeted agents, cytotoxic chemotherapeutic agents, immune checkpoint inhibitors, and peptide receptor radionuclide therapy. In addition, the development of novel molecularly targeted agents is currently in progress. The sequence of selection between different chemotherapy regimens has been of great interest, and resistance to chemotherapeutic agents is the major limitation in their clinical application. Novel agents and high-level clinical evidence continue to emerge in the field of antiangiogenic agents. Peptide receptor radionuclide therapy is increasingly employed for the treatment of advanced neuroendocrine tumors, and greater therapeutic efficacy may be achieved by emerging radio-labeled peptides. Since immune checkpoint inhibitor monotherapies for PanNENs appear to have limited antitumor activity, dual immune checkpoint inhibitor therapies or combinations of antiangiogenic therapies and immune checkpoint inhibitors have been applied in the clinic to improve clinical efficacy. Combining the use of a variety of agents with different mechanisms of action provides new possibilities for clinical treatments. In the future, the study of systemic therapies will continue to focus on the screening of the optimal benefit population and the selection of the best treatment sequence strategy with the aim of truly achieving individualized precise treatment of PanNENs.
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Affiliation(s)
- Yuan-Liang Li
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Zi-Xuan Cheng
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Fu-Huan Yu
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chao Tian
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Huang-Ying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
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15
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Que QY, Zhang LC, Bao JQ, Ling SB, Xu X. Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:397-408. [PMID: 35734618 PMCID: PMC9160682 DOI: 10.4240/wjgs.v14.i5.397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/19/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.
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Affiliation(s)
- Qing-Yang Que
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Lin-Cheng Zhang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Jia-Qi Bao
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Sun-Bin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, Zhejiang Province, China
- Zhejiang University Cancer Center, Hangzhou 310006, Zhejiang Province, China
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310006, Zhejiang Province, China
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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16
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Shi M, Fan Z, Xu J, Yang J, Li Y, Gao C, Su P, Wang X, Zhan H. Gastroenteropancreatic neuroendocrine neoplasms G3: Novel insights and unmet needs. Biochim Biophys Acta Rev Cancer 2021; 1876:188637. [PMID: 34678439 DOI: 10.1016/j.bbcan.2021.188637] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 09/30/2021] [Accepted: 10/14/2021] [Indexed: 12/12/2022]
Abstract
According to the 2019 WHO pathology grading system, high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) can be divided into well differentiated neuroendocrine tumors G3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). GEP-NETs G3 and GEP-NECs present significant differences in driver genes and disease origin. NETs G3 and NECs have been confirmed to be two distinct diseases with different genetic backgrounds, however, this issue remains controversial. The prognosis of NETs G3 is significantly better than that of NECs. The differential diagnosis of GEP-NETs G3 and GEP-NECs should be combined with the patient's medical history, tumor histopathology, Ki-67 index, DAXX/ATRX, TP53 and Rb expression as well as other immunohistochemical indicators. In addition, the treatment strategies of these two subgroups are very different. Here, we summarize recent findings focused on the genomics, clinical manifestations, diagnosis, treatment and other aspects of high-grade GEP-NENs (G3). This review may help further our understanding of the carcinogenesis, diagnosis and treatment of GEP-NENs G3.
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Affiliation(s)
- Ming Shi
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jianwei Xu
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Yongzheng Li
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Changhao Gao
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Peng Su
- Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Xiao Wang
- Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China.
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17
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Das S, Al-Toubah T, Strosberg J. Chemotherapy in Neuroendocrine Tumors. Cancers (Basel) 2021; 13:4872. [PMID: 34638356 PMCID: PMC8507720 DOI: 10.3390/cancers13194872] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/23/2021] [Accepted: 09/24/2021] [Indexed: 12/16/2022] Open
Abstract
The role for cytotoxic chemotherapy in patients with well-differentiated neuroendocrine tumors (NETs) remains debated. Compared to patients with poorly differentiated neuroendocrine carcinomas (NECs) where chemotherapy is utilized ubiquitously, chemotherapy may play a more select role in patients with certain types of NETs (e.g., pancreatic tumors, higher grade tumors, and tumors possessing DNA damage repair defects). The primary types of chemotherapy that have been tested in patients with NETs include alkylating agent- and platinum agent-based combinations. Across regimens, chemotherapy appears to elicit greater antitumor activity in patients with pancreatic or grade 3 NETs. The role for chemotherapy in lower grade extra-pancreatic NETs remains undefined. Furthermore, while chemotherapy has demonstrated clinically meaningful benefit for patients in the systemic setting, its role in the adjuvant or neoadjuvant setting is as-of-yet undetermined. Finally, efforts to combine chemotherapy with targeted therapy and peptide receptor radionuclide therapy are ongoing, in hopes of improving the cytoreductive treatment options for patients with NETs.
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Affiliation(s)
- Satya Das
- Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN 37209, USA;
| | - Taymeyah Al-Toubah
- Moffitt Cancer Center, Department of Gastrointestinal Oncology, Tampa, FL 33612, USA;
| | - Jonathan Strosberg
- Moffitt Cancer Center, Department of Gastrointestinal Oncology, Tampa, FL 33612, USA;
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18
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Lithgow K, Venkataraman H, Hughes S, Shah H, Kemp-Blake J, Vickrage S, Smith S, Humphries S, Elshafie M, Taniere P, Diaz-Cano S, Dasari BVM, Almond M, Ford S, Ayuk J, Shetty S, Shah T, Geh I. Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort. Sci Rep 2021; 11:17947. [PMID: 34504148 PMCID: PMC8429701 DOI: 10.1038/s41598-021-97247-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 06/21/2021] [Indexed: 11/14/2022] Open
Abstract
Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.
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Affiliation(s)
- K Lithgow
- Division of Endocrinology, Department of Medicine, Cumming School of Medicine, 1820 Richmond Rd SW, Calgary, AB, T2T 5C7, Canada.
| | - H Venkataraman
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Hughes
- Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - H Shah
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Kemp-Blake
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Vickrage
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Smith
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Humphries
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M Elshafie
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - P Taniere
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Diaz-Cano
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - B V M Dasari
- Department of Liver Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - M Almond
- Department of General Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Ford
- Department of General Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - J Ayuk
- Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - S Shetty
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - T Shah
- Department of Liver Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - I Geh
- Department of Oncology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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19
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Rinke A, Auernhammer CJ, Bodei L, Kidd M, Krug S, Lawlor R, Marinoni I, Perren A, Scarpa A, Sorbye H, Pavel ME, Weber MM, Modlin I, Gress TM. Treatment of advanced gastroenteropancreatic neuroendocrine neoplasia, are we on the way to personalised medicine? Gut 2021; 70:1768-1781. [PMID: 33692095 DOI: 10.1136/gutjnl-2020-321300] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 12/14/2022]
Abstract
Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups. Translation of this genomic and mechanistic biology into advanced GEPNEN management is limited. 'Targeted' treatments such as somatostatin analogues, peptide receptor radiotherapy, tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are treatment options but predictive tools are lacking. The inability to identify clonal heterogeneity and define critical oncoregulatory pathways prior to therapy, restrict therapeutic efficacy as does the inability to monitor disease status in real time. Chemotherapy in the poor prognosis NEN G3 group, though associated with acceptable response rates, only leads to short-term tumour control and their molecular biology requires delineation to provide new and more specific treatment options.The future requires an exploration of the NEN tumour genome, its microenvironment and an identification of critical oncologic checkpoints for precise drug targeting. In the advance to personalised medical treatment of patients with GEPNEN, clinical trials need to be based on mechanistic and multidimensional characterisation of each tumour in order to identify the therapeutic agent effective for the individual tumour.This review surveys advances in NEN research and delineates the current status of translation with a view to laying the basis for a genome-based personalised medicine management of advanced GEPNEN.
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Affiliation(s)
- Anja Rinke
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
| | - Christoph J Auernhammer
- Department of Internal Medicine IV and Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), Ludwig Maximilian University, LMU Klinikum, Munich, Germany
| | - Lisa Bodei
- Department of Radiology, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Mark Kidd
- Wren Laboratories, Branford, Connecticut, USA
| | - Sebastian Krug
- Clinic for Internal Medicine I, Martin Luther University, Halle, Germany
| | - Rita Lawlor
- Applied Research on Cancer Centre, Department of Pathology and Diagnostics, University of Verona, Verona, Italy
| | - Ilaria Marinoni
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Aurel Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Aldo Scarpa
- Applied Research on Cancer Centre, Department of Pathology and Diagnostics, University of Verona, Verona, Italy
| | - Halfdan Sorbye
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Marianne Ellen Pavel
- Department of Internal Medicine I, Endocrinology, University of Erlangen, Erlangen, Germany
| | - Matthias M Weber
- Department of Internal Medicine I, Endocrinology, Johannes Gutenberg University Hospital Mainz, Mainz, Germany
| | - Irvin Modlin
- Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Thomas M Gress
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
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20
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Wang X, Shi YF, Duan JH, Wang C, Tan HY. S-1 plus temozolomide as second-line treatment for neuroendocrine carcinoma of the breast: A case report. World J Clin Cases 2021; 9:7146-7153. [PMID: 34540971 PMCID: PMC8409205 DOI: 10.12998/wjcc.v9.i24.7146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/27/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine carcinoma of the breast (NECB) is a rare type of malignant tumor. Due to the rarity of NECB, the relevant literature mostly comprises case reports. Available data on treatment options for NECB are very limited. CASE SUMMARY A 62-year-old woman presented to our hospital in October 2016 for intermittent vomiting and diarrhea and masses in the liver found on abdominal computed tomography (CT) imaging. She was diagnosed in July 2012 with neuroendocrine carcinoma of the right breast in local hospital. The patient initially presented with a painful lesion of the right breast. She then undergone surgical resection and adjuvant chemotherapy with pirarubicin and paclitaxel for four cycles as well as endocrine therapy. She was regularly followed every 3 mo after surgery. Enhanced abdominal CT imaging at our hospital revealed multiple suspicious masses in the liver with the largest lesion measuring 8.4 cm × 6.3 cm. Chest CT revealed masses in the anterior chest wall and lung. Core needle biopsy of the lesion revealed liver metastases of NECB. A bone scan showed right second anterior rib metastases. Upper endoscopy and colonoscopy did not provide any evidence of another possible primary tumor. She stopped receiving endocrine therapy and then received etoposide and cisplatin (EP) chemotherapy as a first-line treatment regimen for six cycles at our hospital after liver, bone, and lung metastases. On October 2017, the chemotherapy regimen was changed to S-1 (40 mg twice daily, days 1-14) combined with temozolomide (200 mg once daily, days 10-14) (STEM) every 21 d as a second-line treatment regimen due to disease progression. Progression-free survival (PFS) and adverse effects after treatment were analyzed, and the efficacy of the STEM regimen was assessed using RECIST version 1.1. This patient achieved a partial response after using the STEM regimen, with a PFS of 23 mo. Adverse effects included only grade 1 digestive tract reactions with no need for a reduction in chemotherapy. CONCLUSION This case report suggests that the STEM regimen may be effective and well tolerated as the second-line treatment for advanced NECB. STEM is still highly effective in patients who show disease progression with the EP regimen. More evidence is needed to prove the validity of STEM.
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Affiliation(s)
- Xin Wang
- Beijing University of Chinese Medicine; Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yan-Fen Shi
- Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jiang-Hui Duan
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Chao Wang
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Huang-Ying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
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21
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Shah MH, Goldner WS, Benson AB, Bergsland E, Blaszkowsky LS, Brock P, Chan J, Das S, Dickson PV, Fanta P, Giordano T, Halfdanarson TR, Halperin D, He J, Heaney A, Heslin MJ, Kandeel F, Kardan A, Khan SA, Kuvshinoff BW, Lieu C, Miller K, Pillarisetty VG, Reidy D, Salgado SA, Shaheen S, Soares HP, Soulen MC, Strosberg JR, Sussman CR, Trikalinos NA, Uboha NA, Vijayvergia N, Wong T, Lynn B, Hochstetler C. Neuroendocrine and Adrenal Tumors, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:839-868. [PMID: 34340212 DOI: 10.6004/jnccn.2021.0032] [Citation(s) in RCA: 312] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Neuroendocrine and Adrenal Gland Tumors focus on the diagnosis, treatment, and management of patients with neuroendocrine tumors (NETs), adrenal tumors, pheochromocytomas, paragangliomas, and multiple endocrine neoplasia. NETs are generally subclassified by site of origin, stage, and histologic characteristics. Appropriate diagnosis and treatment of NETs often involves collaboration between specialists in multiple disciplines, using specific biochemical, radiologic, and surgical methods. Specialists include pathologists, endocrinologists, radiologists (including nuclear medicine specialists), and medical, radiation, and surgical oncologists. These guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine and adrenal tumors and are intended to assist with clinical decision-making. This article is focused on the 2021 NCCN Guidelines principles of genetic risk assessment and counseling and recommendations for well-differentiated grade 3 NETs, poorly differentiated neuroendocrine carcinomas, adrenal tumors, pheochromocytomas, and paragangliomas.
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Affiliation(s)
- Manisha H Shah
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | - Pamela Brock
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Paxton V Dickson
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | | | | | | | | | - Jin He
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | - Arash Kardan
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | | | | | | | | | | | | | | | | | | | | | | | - Nikolaos A Trikalinos
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | - Beth Lynn
- National Comprehensive Cancer Network
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22
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Abstract
OPINION STATEMENT Treatment recommendations for advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are based on uncontrolled, mainly retrospective data. Chemotherapy can offer palliative relief, but long-lasting complete responses or cures are rare. The European Neuroendocrine Tumour Society (ENETS) and European Society for Medical Oncology (ESMO) recommend platinum-based chemotherapy as first-line treatment. This has been the golden standard since the late 1980s and has been evaluated in mostly retrospective clinical studies. However, progression is inevitable for most patients. Unfortunately, data on effective second-line treatment options are scant, and ENETS and ESMO recommendations propose fluorouracil- or temozolomide-based chemotherapy schedules. As such, there is a huge unmet need for improved care. Improved knowledge on GEP-NEC biology may provide a pathway towards more effective interventions including chemotherapy, targeted gene therapy, peptide receptor radionuclide therapy, as well as immune checkpoint inhibitors. The review summarises this current state of the art as well as the most promising developments for systemic therapy in GEP-NEC patients.
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23
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Rodriguez-Freixinos V, Thawer A, Capdevila J, Ferone D, Singh S. Advanced Pancreatic Neuroendocrine Neoplasms: Which Systemic Treatment Should I Start With? Curr Oncol Rep 2021; 23:80. [PMID: 33937962 DOI: 10.1007/s11912-021-01071-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/31/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW Pancreatic neuroendocrine neoplasms (panNENs) often present as advanced disease and there is little data to guide treatment sequencing in the advance disease setting. Therefore, we aim to provide a comprehensive summary of the current evidence supporting the use of systemic treatment for patients with diagnosis of advanced and metastatic panNENs, as well as to provide strategies for treatment selection and address challenges for treatment selection and sequencing of therapy. RECENT FINDINGS Substantial advances have been made and many clinical trials have been performed over the past two decades expanding therapeutic options available for patients with advanced panNETs. Available systemic treatments for patients with well-differentiated pancreatic neuroendocrine tumors include somatostatin receptors ligands (SRLs), traditional cytotoxic chemotherapy regimens, peptide receptor radiotherapy (PRRT), and biologically targeted therapies, whereas patients with poorly differentiated neurodocrine carcinomas have more limited treatment options. Despite these advances, no clear guidelines exist to support the best sequence of treatments, not only the first-line, but also subsequent lines of therapy in patients with panNENs. Advances in molecular research and discovery of biomarkers for response allowing a more personalized approach to the multimodality therapy of panNENs are still limited. Understanding the impact of previous therapies on subsequent treatment efficacy and toxicity is also an ongoing research question. In the absence of definite predictive markers and paucity of comparative randomized trials, along with the heterogeneity of this patient population, systemic therapy selection in advanced non-resectable disease should be patient centered and often require evaluation within a multidisciplinary setting. The specific clinical context of the patient, with assessment of individual patient clinical and pathological features, somatostatin receptors imaging, and goals of treatment must all be considered when deciding on systemic therapy in the patient. Additional research is needed to address the gap in knowledge regarding optimal sequencing and timing of therapies and to provide individual care.
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Affiliation(s)
- Victor Rodriguez-Freixinos
- Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada
| | - Alia Thawer
- Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jaume Capdevila
- Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VIHO), Barcelona, Spain
| | - Diego Ferone
- Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.,Endocrinology, Department of Internal Medicine and Medical Specialties (DIMI) and Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy
| | - Simron Singh
- Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
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24
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Garnier H, Loo C, Czauderna P, Vasudevan SA. Pediatric Gastrointestinal Stromal Tumors and Neuroendocrine Tumors: Advances in Surgical Management. Surg Oncol Clin N Am 2021; 30:219-233. [PMID: 33706897 DOI: 10.1016/j.soc.2020.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastrointestinal stromal tumors and neuroendocrine tumors in adult and pediatric populations differ immensely. Despite these established differences, the extreme rarity of gastrointestinal stromal tumors and neuroendocrine tumors in the pediatric population has resulted in the lack of consensus management guidelines, making optimal surgical approaches unclear. Comprehensive management principles to guide surgical approaches in adult literature are extensive. However, these are still lacking for pediatric patients. International cooperation to develop standardized pediatric-specific guidelines is urgently warranted in the future. This article highlights the vast differences between adult and pediatric parameters and provides recommendations on optimal and novel surgical approaches in children.
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Affiliation(s)
- Hanna Garnier
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, Gdańsk 80-210, Poland
| | - Caitlyn Loo
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, 7200 Cambridge Street, 7th Floor, Houston, TX 77030, USA; School of Medicine, Royal College of Surgeons in Ireland, 123 St Stephens Green, Saint Peter's, Dublin D02 YN77, Ireland
| | - Piotr Czauderna
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, Gdańsk 80-210, Poland
| | - Sanjeev A Vasudevan
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, 7200 Cambridge Street, 7th Floor, Houston, TX 77030, USA.
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25
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Merola E, Falconi M, Rinke A, Staettner S, Krendl F, Partelli S, Andreasi V, Gress TM, Pascher A, Arsenic R, Doglioni C, Kaemmerer D, Wiedenmann B, Pavel ME. Radical intended surgery for highly selected stage IV neuroendocrine neoplasms G3. Am J Surg 2020; 220:284-289. [PMID: 32209239 DOI: 10.1016/j.amjsurg.2020.03.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 03/02/2020] [Accepted: 03/04/2020] [Indexed: 01/12/2023]
Abstract
BACKGROUND Stage IV gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) G3 are the NENs with the worst prognosis. According to ENETS guidelines, platinum-based chemotherapy is the standard treatment for this population. Surgery is only considered in highly selected "resectable" NENs with usually lower Ki67. However, the role of surgery with curative intent has been poorly investigated. OBJECTIVE To describe, in a retrospective series of stage IV GEP-NENs G3, overall survival (OS) and recurrence-free survival (RFS) rates after curatively intended surgery. METHODS Multicenter analysis of stage IV GEP-NENs G3 receiving radical resection (R0/R1) from 2007 to 2017, with minimum post-surgical follow-up time of 3 months. RESULTS Fifteen patients from 6 NEN referral centers, with median follow-up of 29 months (8-86), were included. Eight cases had a neuroendocrine carcinoma (NEC) and 7 a neuroendocrine tumor G3 (NET G3). Median OS after radical surgery was 59 months. All patients recurred, with a median RFS of 8 months. CONCLUSIONS Radical surgery might be considered for highly selected stage IV GEP-NENs G3. Larger series are needed to confirm these results.
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Affiliation(s)
- Elettra Merola
- Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; Department of Gastroenterology, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy.
| | - Massimo Falconi
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital IRCCS, Milan, Italy
| | - Anja Rinke
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
| | - Stefan Staettner
- Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Felix Krendl
- Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Stefano Partelli
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital IRCCS, Milan, Italy
| | - Valentina Andreasi
- Pancreatic Surgery Unit, Vita-Salute University, San Raffaele Hospital IRCCS, Milan, Italy
| | - Thomas M Gress
- Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University Hospital Marburg and Philipps University, Marburg, Germany
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Germany; Department of Surgery, Charité Universitätsmedizin, Berlin, Germany
| | - Ruza Arsenic
- Department of Pathology, Charité Mitte, Charité Universitätsmedizin, Berlin, Germany
| | - Claudio Doglioni
- Pathology Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniel Kaemmerer
- Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Bertram Wiedenmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Mitte, Charité Universitätsmedizin, Berlin, Germany
| | - Marianne E Pavel
- Department of Medicine 1, Division of Endocrinology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany; Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Mitte, Charité Universitätsmedizin, Berlin, Germany
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26
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Merola E, Falconi M, Rinke A, Staettner S, Krendl F, Partelli S, Andreasi V, Gress TM, Pascher A, Arsenic R, Doglioni C, Kaemmerer D, Wiedenmann B, Pavel ME. Radical intended surgery for highly selected stage IV neuroendocrine neoplasms G3. Am J Surg 2020; 220:284-289. [DOI: - merola e, falconi m, rinke a, et al.radical intended surgery for highly selected stage iv neuroendocrine neoplasms g3.am j surg.2020 aug;220(2):284-289.doi: 10.1016/j.amjsurg.2020.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
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27
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Halfdanarson TR, Strosberg JR, Tang L, Bellizzi AM, Bergsland EK, O'Dorisio TM, Halperin DM, Fishbein L, Eads J, Hope TA, Singh S, Salem R, Metz DC, Naraev BG, Reidy-Lagunes DL, Howe JR, Pommier RF, Menda Y, Chan JA. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:863-881. [PMID: 32675783 DOI: 10.1097/mpa.0000000000001597] [Citation(s) in RCA: 113] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
This article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.
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Affiliation(s)
| | | | - Laura Tang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Emily K Bergsland
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Thomas M O'Dorisio
- Department of Medicine, Division of Endocrinology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Daniel M Halperin
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Lauren Fishbein
- Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Division of Biomedical Informatics and Personalized Medicine, University of Colorado School of Medicine, Aurora, CO
| | - Jennifer Eads
- Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA
| | - Simron Singh
- Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago IL
| | - David C Metz
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | | | | | - James R Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Rodney F Pommier
- Department of Surgery, Oregon Health and Science University, Portland, OR
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
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28
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Malignant Gastrointestinal Neuroectodermal Tumor (GNET) with Prolonged Disease-Free Survival after Platinum-Based Chemotherapy. Case Rep Oncol Med 2020; 2020:8880202. [PMID: 32665870 PMCID: PMC7349616 DOI: 10.1155/2020/8880202] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/07/2020] [Accepted: 05/29/2020] [Indexed: 01/12/2023] Open
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare disease with a handful of cases described in literature. GNET has only become a well-known/widely accepted entity in the recent years, but it is still not listed in the database of rare diseases. Due to the rarity of disease, there are no guidelines on standard therapeutic approaches in the adjuvant or metastatic setting. Here, we describe a unique case of GNET with a 7-year disease-free survival following adjuvant cisplatin and etoposide chemotherapy. This is the longest disease-free survival that has ever been described in literature and may support using this combination in a larger cohort of patients in the context of a global clinical trial. We will also review the histopathologic features of GNET and potential therapeutic options in the metastatic setting.
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29
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Chatzellis E, Daskalakis K, Angelousi A, Tsoli M, Alexandraki KI, Wachula E, Meirovitz A, Maimon O, Grozinsky-Glasberg S, Gross D, Kos-Kudła B, Koumarianou A, Kaltsas G. Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms: The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms". Neuroendocrinology 2020; 110:158-160. [PMID: 31597137 DOI: 10.1159/000503999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 10/09/2019] [Indexed: 11/19/2022]
Affiliation(s)
- Eleftherios Chatzellis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece,
- 251 HAF and VA Hospital, Athens, Greece,
| | - Kosmas Daskalakis
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Anna Angelousi
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Marina Tsoli
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Krystallenia I Alexandraki
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ewa Wachula
- Department of Clinical Oncology and Radiotherapy, Medical University of Silesia, Katowice, Poland
| | - Amichay Meirovitz
- Oncology Department and Radiation Therapy Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Ofra Maimon
- Oncology Department and Radiation Therapy Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - David Gross
- Neuroendocrine Tumor Unit, Department of Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Beata Kos-Kudła
- Department of Endocrinology and Neuroendocrine Neoplasms, Medical University of Silesia, Katowice, Poland
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland
- Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland
| | - Anna Koumarianou
- Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gregory Kaltsas
- First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
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30
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Das S, Al-Toubah T, El-Haddad G, Strosberg J. 177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert Rev Gastroenterol Hepatol 2019; 13:1023-1031. [PMID: 31652074 PMCID: PMC7227421 DOI: 10.1080/17474124.2019.1685381] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 10/22/2019] [Indexed: 12/14/2022]
Abstract
Introduction: 177Lutetium-[DOTA°,Tyr3]octreotate (177Lu-DOTATATE) is a type of peptide receptor radionuclide therapy that garnered FDA approval in January 2018 for the treatment of somatostatin receptor-positive gastroenteropancreatic (GEP) neuroendocrine tumor (NET) patients. The therapy approval was based on findings from the randomized international phase III NETTER-1 trial as well as outcome data from a large European registry. The mechanism of the drug stems directly from its structure: a somatostatin analog (octreotate) selectively binding to somatostatin receptor expressing cells and being internalized, along with a chelated beta-emitting isotope 177Lu.Areas Covered: Herein we describe the pharmacology, clinical efficacy and adverse event data from prospective and retrospective studies with 177Lu-DOTATATE. We discuss the role of 177Lu-DOTATATE within the current treatment landscape for GEP NET patients.Expert Opinion: 177Lu-DOTATATE represents a unique addition to the treatment armamentarium for GEP NETs because of its potential to elicit tumor cytoreduction, which is rare among other existing treatment options, and prolonged disease control. Where 177Lu-DOTATATE fits into the treatment sequence for GEP NET patients remains an area of active investigation.
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Affiliation(s)
- Satya Das
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Ghassan El-Haddad
- Department of Interventional Radiology and Nuclear Medicine, Moffitt Cancer Center, Tampa, FL, USA
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31
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Sonbol MB, Halfdanarson TR. Management of Well-Differentiated High-Grade (G3) Neuroendocrine Tumors. Curr Treat Options Oncol 2019; 20:74. [PMID: 31428952 DOI: 10.1007/s11864-019-0670-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OPINION STATEMENT In 2017, the World Health Organization (WHO) classification for pancreatic NET was updated to include a new category of well-differentiated high-grade (Ki 67 > 20%) pancreatic tumors (NET G3), distinct from high-grade poorly differentiated neuroendocrine carcinoma (NEC). NET G3 are considered a molecularly, radiologically, and prognostically distinct entity compared to NEC and NET G1/G2. The optimal first-line management in NET G3 and sequencing therapies remains a challenge awaiting future trials taking into consideration the unique characteristics of this category. In this review, we aim to summarize the current evidence in the management of NET G3.
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