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Acher AW, Hallet J. Advances in Management of Nonfunctional Pancreas Neuroendocrine Tumors. Surg Clin North Am 2024; 104:1095-1111. [PMID: 39237166 DOI: 10.1016/j.suc.2024.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
This article presents updates in the surgical management of non-functional sporadic pancreas neuroendocrine tumors NET, including considerations for assessment of biologic behavior to support decision-making, indications for surgery, and surgical approaches tailored to the unique nature of neuroendocrine tumors.
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Affiliation(s)
- Alexandra W Acher
- Department of Surgery, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5
| | - Julie Hallet
- Department of Surgery, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5; Susan Leslie Clinic for Neuroendocrine Tumors, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
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Yan Y, Wu D, Wang W, Lv Y, Yang L, Liu Y, Dong P, Yu X. Efficacy and safety of neoadjuvant therapy in gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. J Cancer Res Ther 2024; 20:633-641. [PMID: 38687934 DOI: 10.4103/jcrt.jcrt_1800_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 12/01/2023] [Indexed: 05/02/2024]
Abstract
OBJECTIVE To determine the effectiveness and safety of neoadjuvant therapy in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) and provide evidence-based suggestions for clinical treatment. METHODS The Cochrane Library, Embase, PubMed, and Web of Science were searched for articles published that analyzed the effectiveness and safety of GEP-NEN-targeted neoadjuvant therapy before March 2023. A confidence interval (CI) of 95%, a subgroup analysis, heterogeneity, and effect size (ES) were analyzed, and a meta-analysis of the literature was performed using the Stata BE17 software. RESULTS A total of 417 patients from 13 studies were included in this meta-analysis. The primary variables comprised the objective response rate (ORR), disease control rate (DCR), surgical resection rate, and R0 resection rate with ES values of 0.42 (95% CI: 0.25-0.60), 0.96 (95% CI: 0.93-0.99), 0.67 (95% CI: 0.50-0.84), and 0.60 (95% CI: 0.54-0.67), respectively. The secondary variables were the incidence rates of treatment-related adverse events (TRAEs), Grade 3 or higher TRAEs, and surgical complications with ES values of 0.29 (95% CI: -0.03-0.21), 0.13 (95% CI: -0.07-0.33), and 0.35 (95% CI: 0.27-0.44), respectively. CONCLUSION Neoadjuvant therapy is an effective and safe treatment method for GEP-NENs. However, further studies are required to determine the optimal regimen for this therapy in these tumors.
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Affiliation(s)
- Yu Yan
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, Shandong, China
| | - Danzhu Wu
- Clinical Medical College, Jining Medical University, Jining, China
| | - Weizhen Wang
- Department of Pediatric Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yajuan Lv
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, Shandong, China
| | - Liyuan Yang
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, Shandong, China
| | - Yinglong Liu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, Shandong, China
| | - Peng Dong
- Clinical Medical College, Shandong First Medical University and Shandong Academy of Medical Sciences, Taian, Shandong, China
| | - Xinshuang Yu
- Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, Shandong, China
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Yit LFN, Li Y. A Review of the Evolving Role of Radiotherapy in the Treatment of Neuroendocrine Neoplasms. Neuroendocrinology 2024; 114:856-865. [PMID: 38432216 DOI: 10.1159/000538140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are rare tumours that develop from neuroendocrine cells in various parts of the body. The management of this disease poses a significant challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. A multidisciplinary approach is often required in complex clinical situations. Radiotherapy (RT) plays a key role in managing NETs in both curative and palliative settings. SUMMARY In this review, we summarize and discuss recent developments in the field of advanced RT in early-stage, locally advanced, and metastatic NENs. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NENs.
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Affiliation(s)
- Ling Fung Nelson Yit
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Youquan Li
- Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
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Alexander ES, Ziv E. Neuroendocrine Tumors: Genomics and Molecular Biomarkers with a Focus on Metastatic Disease. Cancers (Basel) 2023; 15:cancers15082249. [PMID: 37190177 DOI: 10.3390/cancers15082249] [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: 03/07/2023] [Revised: 04/08/2023] [Accepted: 04/08/2023] [Indexed: 05/17/2023] Open
Abstract
Neuroendocrine tumors (NETs) are considered rare tumors that originate from specialized endocrine cells. Patients often present with metastatic disease at the time of diagnosis, which negatively impacts their quality of life and overall survival. An understanding of the genetic mutations that drive these tumors and the biomarkers used to detect new NET cases is important to identify patients at an earlier disease stage. Elevations in CgA, synaptophysin, and 5-HIAA are most commonly used to identify NETs and assess prognosis; however, new advances in whole genome sequencing and multigenomic blood assays have allowed for a greater understanding of the drivers of NETs and more sensitive and specific tests to diagnose tumors and assess disease response. Treating NET liver metastases is important in managing hormonal or carcinoid symptoms and is imperative to improve patient survival. Treatment for liver-dominant disease is varied; delineating biomarkers that may predict response will allow for better patient stratification.
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Affiliation(s)
- Erica S Alexander
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
| | - Etay Ziv
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
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Li Y, Fan Z, Zhang F, Yang J, Shi M, Liu S, Meng Y, Zhan H. Neoadjuvant therapy in pancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Front Oncol 2022; 12:981575. [PMID: 36505835 PMCID: PMC9731099 DOI: 10.3389/fonc.2022.981575] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/08/2022] [Indexed: 11/25/2022] Open
Abstract
Background and Objectives Neoadjuvant therapy plays an increasingly important role in pancreatic neuroendocrine neoplasms (pNENs), but the systematic evaluation of its efficacy is still lacking. The purpose of this study is to explore the role of neoadjuvant therapy in pNENs. Methods We systematically reviewed the literatures published online until October 1, 2021. Meta-analysis was conducted to generate proportion with 95% confidence intervals (95% CI) for tumor response, resection rate, R0 resection rate and survival time. Results Nine studies with 468 patients were involved in the systematic review. None of these patients met complete response (CR). Furthermore, 43.6% (95% CI [18.1, 69.0]) patients were expected to achieve partial response (PR), 51.3% (95% CI [27.9, 78.3]) to stable disease (SD), and 4.3% (95% CI [0.7, 7.9]) to progressive disease (PD). The estimate resection rate and R0 resection rate after neoadjuvant therapy were 68.2% (95% CI [44.5, 91.9]) and 60.2% (95% CI [53.5, 66.9]), respectively. There was no significant difference in resection rate between different chemotherapy regimens (41.67% vs 33.93%, P=0.453), as well as R0 resection rate (62.50% vs 68.30%, P=0.605). In terms of objective response rate (ORR), there was no significant difference between CAPTEM and FAS (41.67% vs 33.93%, P=0.453), while PRRT showed a higher ORR compared with chemotherapy, although there was also no statistical difference (49.06% vs 36.96%, P=0.154). Conclusion Neoadjuvant therapies could reduce the tumor size and stage of some borderline resectable or unresectable pNENs, and give some patients the chance of radical resection. However, according to the current data, the best treatment regimen for pNENs neoadjuvant therapy is still unknown.
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Affiliation(s)
- Yongzheng Li
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhiyao Fan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Feifei Zhang
- The First Operating Theater, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Jian Yang
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Ming Shi
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Shujie Liu
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yufan Meng
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Hanxiang Zhan
- Division of Pancreatic Surgery, Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China,*Correspondence: Hanxiang Zhan,
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Siebenhüner AR, Langheinrich M, Friemel J, Schaefer N, Eshmuminov D, Lehmann K. Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors-Need for a Conductor. Cancers (Basel) 2022; 14:1478. [PMID: 35326628 PMCID: PMC8946777 DOI: 10.3390/cancers14061478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/28/2022] [Accepted: 03/10/2022] [Indexed: 12/11/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a vast growing disease. Over 50% of these tumors are recognized at advanced stages with lymph node, liver, or distant metastasis. An ongoing controversy is the role of surgery in the metastatic setting as dedicated systemic treatments have emerged recently and shown benefits in randomized trials. Today, liver surgery is an option for advanced pNETs if the tumor has a favorable prognosis, reflected by a low to moderate proliferation index (G1 and G2). Surgery in this well-selected population may prolong progression-free and overall survival. Optimal selection of a treatment plan for an individual patient should be considered in a multidisciplinary tumor board. However, while current guidelines offer a variety of modalities, there is so far only a limited focus on the right timing. Available data is based on small case series or retrospective analyses. The focus of this review is to highlight the right time-point for surgery in the setting of the multimodal treatment of an advanced pancreatic neuroendocrine tumor.
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Affiliation(s)
- Alexander R. Siebenhüner
- Clinic for Gastroenterology and Hepatology, University Hospital Zurich and University of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Melanie Langheinrich
- Department of Visceral Surgery, University Hospital Greifswald, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany;
| | - Juliane Friemel
- Institute for Pathologie, University Bern, Murtenstrasse 31, CH-3008 Bern, Switzerland;
| | - Niklaus Schaefer
- Department of Nuclear Medicine, University Hospital Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland;
| | - Dilmurodjon Eshmuminov
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
| | - Kuno Lehmann
- ENETS Center of Excellence Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
- Department of Surgery and Transplantation, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland;
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Geleta B, Tout FS, Lim SC, Sahni S, Jansson PJ, Apte MV, Richardson DR, Kovačević Ž. Targeting Wnt/tenascin C-mediated cross talk between pancreatic cancer cells and stellate cells via activation of the metastasis suppressor NDRG1. J Biol Chem 2022; 298:101608. [PMID: 35065073 PMCID: PMC8881656 DOI: 10.1016/j.jbc.2022.101608] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/02/2022] [Accepted: 01/05/2022] [Indexed: 02/06/2023] Open
Abstract
A major barrier to successful pancreatic cancer (PC) treatment is the surrounding stroma, which secretes growth factors/cytokines that promote PC progression. Wnt and tenascin C (TnC) are key ligands secreted by stromal pancreatic stellate cells (PSCs) that then act on PC cells in a paracrine manner to activate the oncogenic β-catenin and YAP/TAZ signaling pathways. Therefore, therapies targeting oncogenic Wnt/TnC cross talk between PC cells and PSCs constitute a promising new therapeutic approach for PC treatment. The metastasis suppressor N-myc downstream-regulated gene-1 (NDRG1) inhibits tumor progression and metastasis in numerous cancers, including PC. We demonstrate herein that targeting NDRG1 using the clinically trialed anticancer agent di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) inhibited Wnt/TnC-mediated interactions between PC cells and the surrounding PSCs. Mechanistically, NDRG1 and DpC markedly inhibit secretion of Wnt3a and TnC by PSCs, while also attenuating Wnt/β-catenin and YAP/TAZ activation and downstream signaling in PC cells. This antioncogenic activity was mediated by direct inhibition of β-catenin and YAP/TAZ nuclear localization and by increasing the Wnt inhibitor, DKK1. Expression of NDRG1 also inhibited transforming growth factor (TGF)-β secretion by PC cells, a key mechanism by which PC cells activate PSCs. Using an in vivo orthotopic PC mouse model, we show DpC downregulated β-catenin, TnC, and YAP/TAZ, while potently increasing NDRG1 expression in PC tumors. We conclude that NDRG1 and DpC inhibit Wnt/TnC-mediated interactions between PC cells and PSCs. These results further illuminate the antioncogenic mechanism of NDRG1 and the potential of targeting this metastasis suppressor to overcome the oncogenic effects of the PC-PSC interaction.
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Affiliation(s)
- Bekesho Geleta
- Cancer Metastasis and Tumor Microenvironment Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia
| | - Faten S Tout
- Cancer Metastasis and Tumor Microenvironment Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Department of Medical Laboratory Science, Faculty of Allied Health Sciences, The Hashemite University, Zarqa, Jordan
| | - Syer Choon Lim
- Cancer Metastasis and Tumor Microenvironment Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia
| | - Sumit Sahni
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
| | - Patric J Jansson
- Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia; Cancer Drug Resistance & Stem Cell Program, Faculty of Medicine and Health, School of Medical Science, University of Sydney, Sydney, New South Wales, Australia
| | - Minoti V Apte
- Pancreatic Research Group, South Western Sydney Clinical School, UNSW Sydney, Sydney, New South Wales, Australia; Pancreatic Research Group, Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia
| | - Des R Richardson
- Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Centre for Cancer Cell Biology and Drug Discovery, Griffith Institute for Drug Discovery, Griffith University, Nathan, Brisbane, Queensland, Australia; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Žaklina Kovačević
- Cancer Metastasis and Tumor Microenvironment Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia; Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [DOI: - merola e, michielan a, rozzanigo u, et al.therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: state-of-the-art and future perspectives.world j gastrointestinal surgery, volume 14 number 2 february 27, 2022, doi: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [PMID: 35317548 PMCID: PMC8908345 DOI: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 10/18/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Andrea Michielan
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Umberto Rozzanigo
- Department of Radiology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Marco Erini
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Sandro Sferrazza
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Stefano Marcucci
- Department of Surgery, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Sartori
- Department of Pathology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Giovanni de Pretis
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Franca Chierichetti
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
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Opalińska M, Sowa-Staszczak A, Grochowska A, Olearska H, Hubalewska-Dydejczyk A. Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors. Front Oncol 2021; 11:687925. [PMID: 34868906 PMCID: PMC8633407 DOI: 10.3389/fonc.2021.687925] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 10/21/2021] [Indexed: 02/01/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes. AIM This study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs. METHODS Among the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment. RESULTS Neoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved. CONCLUSION PRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.
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Affiliation(s)
- Marta Opalińska
- Nuclear Medicine Unit, Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Kraków, Poland
| | - Anna Sowa-Staszczak
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
| | - Anna Grochowska
- Department of Radiology, University Hospital, Kraków, Poland
| | - Helena Olearska
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
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11
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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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Chen D, Zhao H. The inhibiting effects of microRNA-429 on the progression of pancreatic ductal adenocarcinoma cells by inhibiting epithelial mesenchymal transition. Am J Transl Res 2021; 13:3286-3293. [PMID: 34017500 PMCID: PMC8129377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/02/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To research the effects and related mechanism of microRNA (miRNA)-429 in the development of pancreatic ductal adenocarcinoma (PDAC). METHODS The proliferation and invasion ability of cells were evaluated through MTT assay and transwell assay, respectively. The expression of proteins and mRNA were examined by immunofluorescence, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The effects and potential mechanism of miR-429 in PDAC cells were explored and evaluated. Our study suggested that miR-429 is closely related with the progression of cancer. Overexpressed miR-429 restricted the mobility and proliferation of PDAC cells by restricting EMT, while down-regulated miR-429 had the opposite effect. These above results implied that miR-429 suppresses the development of PDAC by regulating EMT. CONCLUSION MiR-429 inhibits the progression of PDAC cells by regulating EMT. Our study provided a novel potential mechanism for the occurrence of PDAC and laid the foundation for the development of miRNA targeted therapy in patients with PDAC.
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Affiliation(s)
- Dong Chen
- Department of General Surgery, Shanxi Bethune Hospital Taiyuan, Shanxi Province, China
| | - Haoliang Zhao
- Department of General Surgery, Shanxi Bethune Hospital Taiyuan, Shanxi Province, China
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13
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Neutrophil-lymphocyte ratio (NLR) was associated with prognosis and immunomodulatory in patients with pancreatic ductal adenocarcinoma (PDAC). Biosci Rep 2021; 40:225197. [PMID: 32510138 PMCID: PMC7300287 DOI: 10.1042/bsr20201190] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 05/27/2020] [Accepted: 06/01/2020] [Indexed: 02/07/2023] Open
Abstract
Although the oncological outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) have markedly improved over the past decade, the survival prediction is still challenging. The aim of this study was to investigate the prognostic value of neutrophil–lymphocyte ratio (NLR) and analyze the relationship of between the NLR and immune cells phenotypes in patients with PDAC. Sixty-seven consecutive patients with PDAC were recruited in this study. Life-table estimates of survival time were calculated according to the Kaplan and Meier methodology. The phenotypic T cells subclasses were evaluated by flow cytometry. All the 67 patients in this study were treated with surgical resection and among them, 46 patients received adjuvant chemotherapy. Receiver operating characteristic (ROC) curves analysis was performed to compare prognostic value of NLR with CA199. We found that the Harrell's area under ROC (AUROC) for the NLR to predict overall survival (OS) (0.840; 95% CI, 0.766–0.898) was significantly higher than that of the CA199 levels. After that we stratified all patients into NLR > 2.5 (n = 42) and NLR ≤ 2.5 (n = 25) groups according to the OS of patients with PDAC. Survival analysis showed that patients with NLR ≤ 2.5 had significantly favorable OS and progressive free survival (PFS) compared with patients with NLR > 2.5. The CD3+ and CD8+/CD28+ T cell subsets were significantly increased in patients with NLR ≤ 2.5 (P<0.05), while the CD8+/CD28- and CD4+/CD25+ cell subsets were significantly decreased in patients with NLR ≤ 2.5 (P<0.05). In conclusion, a high NLR value independently predicts poor survival in patients with PDAC after surgical resection. The NLR was closely related with immune cells phenotypes The NLR may help oncologists evaluate outcomes of patients received surgical resection and chemotherapy to choose alternative therapies for patients with high NLR value.
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Lania A, Ferraù F, Rubino M, Modica R, Colao A, Faggiano A. Neoadjuvant Therapy for Neuroendocrine Neoplasms: Recent Progresses and Future Approaches. Front Endocrinol (Lausanne) 2021; 12:651438. [PMID: 34381421 PMCID: PMC8350565 DOI: 10.3389/fendo.2021.651438] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors, their treatment being challenging and requiring a multidisciplinary approach. Though the only curative treatment is surgery, up to 50% of patients are diagnosed with metastatic disease. In the last years, neoadjuvant chemo(radio)therapy has become part of the standard of care in the treatment of different cancer types. However, evidence of its efficacy and safety in NEN patients has not yet been confirmed in the literature. The aim of the present review is to perform an extensive review of the scientific evidence for neoadjuvant therapy in patients with gastroenteropancreatic and thoracic NENs.
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Affiliation(s)
- Andrea Lania
- Endocrinology, Diabetology and Andrology Unit, Humanitas Clinical and Research Center—IRCCS, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
- *Correspondence: Andrea Lania,
| | - Francesco Ferraù
- Department of Human Pathology of Adulthood and Childhood ‘G. Barresi’, University of Messina, Messina, Italy
- Endocrine Unit, University Hospital G. Martino, Messina, Italy
| | - Manila Rubino
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Roberta Modica
- Endocrinology, Department of Clinical Medicine and Surgery, “Federico II” University of Napoli, Napoli, Italy
| | - Annamaria Colao
- Endocrinology, Department of Clinical Medicine and Surgery, “Federico II” University of Napoli, Napoli, Italy
| | - Antongiulio Faggiano
- Endocrinology, Department of Experimental Medicine, “Sapienza”, University of Rome, Rome, Italy
- Department of Experimental Medicine, Division of Medical Physiopathology, Sapienza University of Rome, Rome, Italy
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15
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Titan AL, Norton JA, Fisher AT, Foster DS, Harris EJ, Worhunsky DJ, Worth PJ, Dua MM, Visser BC, Poultsides GA, Longaker MT, Jensen RT. Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors. JAMA Netw Open 2020; 3:e2024318. [PMID: 33146734 PMCID: PMC7643030 DOI: 10.1001/jamanetworkopen.2020.24318] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need. OBJECTIVE To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs. DESIGN, SETTING, AND PARTICIPANTS This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019. MAIN OUTCOMES AND MEASURES Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates. RESULTS In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P < .001), additional organ resected (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003) were associated with increased risk of recurrence. Functional tumors had a lower risk of recurrence (HR, 0.23; CI, 0.06-0.89; P = .03). Required resection of blood vessels was not associated with a significant increase recurrence risk. CONCLUSIONS AND RELEVANCE In this case series, positive lymph node involvement and resection of organs with tumor involvement were associated with an increased recurrence risk. These subgroups may require adjuvant systemic treatment. These findings suggest that patients with locally advanced PNETs who undergo surgical resection have excellent disease-free and overall survival.
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Affiliation(s)
- Ashley L. Titan
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Jeffrey A. Norton
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Andrea T. Fisher
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Deshka S. Foster
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - E. John Harris
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | - Patrick J. Worth
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Monica M. Dua
- Department of Surgery, Stanford University Hospital, Stanford, California
| | - Brendan C. Visser
- Department of Surgery, Stanford University Hospital, Stanford, California
| | | | | | - Robert T. Jensen
- Gastrointestinal Cell Biology Section, National Institutes of Health, Bethesda, Maryland
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16
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Zhang MY, He D, Zhang S. Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment. World J Gastrointest Oncol 2020; 12:705-718. [PMID: 32864039 PMCID: PMC7428799 DOI: 10.4251/wjgo.v12.i7.705] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/17/2020] [Accepted: 06/17/2020] [Indexed: 02/05/2023] Open
Abstract
In 2017 the World Health Organization revised the criteria for classification of pancreatic neuroendocrine neoplasms (pNENs) after a consensus conference at the International Agency for Research on Cancer. The major change in the new classification was to subclassify the original G3 group into well-differentiated pancreatic neuroendocrine tumors G3 (pNETs G3) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), which have been gradually proven to be completely different in biological behavior and clinical manifestations in recent years. In 2019 this major change subsequently extended to NENs involving the entire digestive tract. The updated version of the pNENs grading system marks a growing awareness of these heterogeneous tumors. This review discusses the clinicopathological, genetic and therapeutic features of poorly differentiated pNECs and compare them to those of well-differentiated pNETs G3. For pNETs G3 and pNECs (due to their lower incidence), there are still many problems to be investigated. Previous studies under the new grading classification also need to be reinterpreted. This review summarizes the relevant literature from the perspective of the differences between pNETs G3 and pNECs in order to deepen understanding of these diseases and discuss future research directions.
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Affiliation(s)
- Ming-Yi Zhang
- Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Du He
- Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Shuang Zhang
- Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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17
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Abstract
The increased incidence and prevalence of neuroendocrine tumors (NETs) over the past few decades has been accompanied by an improvement in overall survival. There are differences in the management of small bowel NETs versus pNETs. The management of all patients with NETs must be individualized based on patient characteristics as well tumor-related factors. This article reviews the role of somatostatin analogues, historical results with chemotherapy in gastroenteropancreatic NETs (GEPNETs), and more recent evidence for the use of cytotoxic chemotherapy in GEPNETs. The article also discusses molecular targeted therapies approved for use in GEPNETs and some ongoing clinical trials.
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Affiliation(s)
- Chandrikha Chandrasekharan
- Division of Medical Oncology, University of Iowa, 200 Hawkins Drive, C GH 32, Iowa City, Iowa 52242, USA.
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18
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Howe JR, Merchant NB, Conrad C, Keutgen XM, Hallet J, Drebin JA, Minter RM, Lairmore TC, Tseng JF, Zeh HJ, Libutti SK, Singh G, Lee JE, Hope TA, Kim MK, Menda Y, Halfdanarson TR, Chan JA, Pommier RF. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:1-33. [PMID: 31856076 PMCID: PMC7029300 DOI: 10.1097/mpa.0000000000001454] [Citation(s) in RCA: 259] [Impact Index Per Article: 51.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
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Affiliation(s)
- James R. Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Claudius Conrad
- Department of Surgery, St. Elizabeth Medical Center, Tufts University School of Medicine, Boston, MA
| | | | - Julie Hallet
- Department of Surgery, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jeffrey A. Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rebecca M. Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | | | - Herbert J. Zeh
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven K. Libutti
- §§ Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Gagandeep Singh
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A. Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
| | - Michelle K. Kim
- Department of Medicine, Mt. Sinai Medical Center, New York, NY
| | - 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
| | - Rodney F. Pommier
- Department of Surgery, Oregon Health & Sciences University, Portland, OR
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19
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Xie H, Liu J, Yadav S, Keutgen XM, Hobday TJ, Strosberg JR, Halfdanarson TR. The Role of Perioperative Systemic Therapy in Localized Pancreatic Neuroendocrine Neoplasms. Neuroendocrinology 2020; 110:234-245. [PMID: 31121586 DOI: 10.1159/000501126] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 05/23/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND The role of perioperative systemic therapy (PST) in the management of localized pancreatic neuroendocrine neoplasms (PanNEN) is unclear. OBJECTIVES We aimed to evaluate the benefit of PST compared to surgery alone (SA) in patients with localized PanNEN. METHOD We selected patients with stages I-III PanNEN who underwent curative-intent surgical resection in National Cancer Database from 2006 to 2014. Patients who had both PST and surgical resection were matched with patients who received SA by propensity score at 1-to-1 ratio with nearest neighbor method. RESULTS Four thousand eight hundred and ninety-two patients were included in this study with median age of 60 years. Factors associated with significant more use of PST compared to SA included age <65 years, community medical facilities, grade 3 tumor, tumor in the pancreatic head, T34 tumor, and N1 tumor. Three hundred and one PST patients were matched with 301 SA patients. In the matched cohort, the PST group had significantly shorter overall survival (OS) compared to the SA group (median overall both not reached, p = 0.037). This finding was confirmed by multivariable Cox proportional hazards regression in the original cohort (hazard ratio [HR] 1.45, 95% CI 1.11-1.89, p = 0.006). Subgroup analyses showed that adjuvant therapy was not associated with improved OS in grades 1-2 PanNEN (HR 2.03, 95% CI 1.31-3.16, p = 0.002). CONCLUSIONS PST stratified by grade and neoadjuvant or adjuvant therapy compared to SA was not associated with improved OS in patients with localized PanNEN. PST for localized PanNEN should be used with caution until prospective data are available.
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Affiliation(s)
- Hao Xie
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Junjia Liu
- New York University, New York, New York, USA
| | - Siddhartha Yadav
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Xavier M Keutgen
- Department of Surgery, Endocrine Research Program, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Timothy J Hobday
- Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jonathan R Strosberg
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
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Abstract
PURPOSE OF REVIEW Pancreatic neuroendocrine tumors (pNETs) are a rare, heterogeneous group of pancreatic neoplasms with a wide range of malignant potential. They may manifest as noninfiltrative, slow-growing tumors, locally invasive masses, or even swiftly metastasizing cancers. RECENT FINDINGS In recent years, because of the increasing amount of scientific literature available for pNETs, the classification, prognostic stratification criteria, and available consensus guidelines for diagnosis and therapy have been revised and updated. SUMMARY The vast majority of new pNET diagnoses consist of incidentally discovered lesions on cross-sectional imaging. The biologic behavior of pNETs is defined by the grade and stage of the tumor. Surgery is the only curative treatment and it, therefore, represents the first therapeutic choice for any localized pNET; however, recent evidence suggests that patients with small (<2 cm), nonfunctioning G1 tumors can be safely observed.An aggressive surgical approach towards liver metastases is recommended in selected cases, as well as liver-directed therapies for disease control. In the presence of unresectable progressive disease, somatostatin analogs, targeted therapies such as everolimus, peptide receptor radionuclide therapy, and systemic chemotherapy are all useful tools for prolonging survival.
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21
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Perspective of neo-adjuvant/conversion and adjuvant therapy for pancreatic neuroendocrine tumors. JOURNAL OF PANCREATOLOGY 2019. [DOI: 10.1097/jp9.0000000000000023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
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22
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Rozenblum L, Mokrane FZ, Yeh R, Sinigaglia M, Besson F, Seban RD, Chougnet CN, Revel-Mouroz P, Zhao B, Otal P, Schwartz LH, Dercle L. The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI. Abdom Radiol (NY) 2019; 44:2474-2493. [PMID: 30980115 DOI: 10.1007/s00261-019-01994-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that secrete peptides and neuro-amines. pNETs can be sporadic or hereditary, syndromic or non-syndromic with different clinical presentations and prognoses. The role of medical imaging includes locating the tumor, assessing its extent, and evaluating the feasibility of curative surgery or cytoreduction. Pancreatic NETs have very distinctive phenotypes on CT, MRI, and PET. PET have been demonstrated to be very sensitive to detect either well-differentiated pNETs using 68Gallium somatostatin receptor (SSTR) radiotracers, or more aggressive undifferentiated pNETS using 18F-FDG. A comprehensive interpretation of multimodal imaging guides resectability and cytoreduction in pNETs. The imaging phenotype provides information on the differentiation and proliferation of pNETs, as well as the spatial and temporal heterogeneity of tumors with prognostic and therapeutic implications. This review provides a structured approach for standardized reading and reporting of medical imaging studies with a focus on PET and MR techniques. It explains which imaging approach should be used for different subtypes of pNET and what a radiologist should be looking for and reporting when interpreting these studies.
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Affiliation(s)
- Laura Rozenblum
- Sorbonne Université, Service de Médecine Nucléaire, AP-HP, Hôpital La Pitié-Salpêtrière, 75013, Paris, France
| | - Fatima-Zohra Mokrane
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Randy Yeh
- Memorial Sloan Kettering Cancer Center, Molecular Imaging and Therapy Service, New York, NY, USA
| | - Mathieu Sinigaglia
- Department of Imaging and Nuclear Medicine, Institut Claudius Regaud - Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
| | - Florent Besson
- Paris Sud University, Kremlin Bicêtre Hospital, Paris, France
| | - Romain-David Seban
- Department of Nuclear Medicine, Institut Curie-René Huguenin, Saint-Cloud, France
| | - Cecile N Chougnet
- Department of Endocrine Oncology, Hôpital Saint Louis, Paris, France
| | - Paul Revel-Mouroz
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
| | - Binsheng Zhao
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Philippe Otal
- Radiology Department, Toulouse University Hospital, 1 Avenue du Professeur Jean Poulhes, 31059, Toulouse, France
| | - Lawrence H Schwartz
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA
| | - Laurent Dercle
- Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY, USA.
- UMR 1015, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, 94805, France.
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23
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Jensen RT, Bodei L, Capdevila J, Couvelard A, Falconi M, Glasberg S, Kloppel G, Lamberts S, Peeters M, Rindi G, Rinke A, Rothmund M, Sundin A, Welin S, Fazio N. Unmet Needs in Functional and Nonfunctional Pancreatic Neuroendocrine Neoplasms. Neuroendocrinology 2018; 108:26-36. [PMID: 30282083 DOI: 10.1159/000494258] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 09/26/2018] [Indexed: 12/17/2022]
Abstract
Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.
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Affiliation(s)
- Robert T Jensen
- Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland,
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Jaume Capdevila
- Department of Medical Oncology, Vall d'Hebron University Hospital, Vall Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Massimo Falconi
- Chirurgia del Pancreas, Università Vita e Salute, San Raffaele Hospital IRCCS, Milan, Italy
| | - Simona Glasberg
- Neuroendocrine Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Günter Kloppel
- Institute of Pathology, Technische Universität München, Munich, Germany
| | - Steven Lamberts
- Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Marc Peeters
- Department of Oncology, Antwerp University Hospital, Edegem, Belgium
| | - Guido Rindi
- Institute of Anatomic Pathology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Anja Rinke
- Department of Gastroenterology, UKGM Marburg and Philipps University, Marburg, Germany
| | | | - Anders Sundin
- Department of Radiology, Institute of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Staffan Welin
- Endocrine Oncology Unit, Department of Medical Sciences, University Hospital, Uppsala, Sweden
| | - Nicola Fazio
- Gastrointestinal and Neuroendocrine Oncology Unit, European Institute of Oncology (IEO), Milan, Italy
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Zhang H, Shen G, Zhang S, Du F, Cao Y, Jiang J, Zheng F, Ma X, Wang Z, Ren D, Ahmad R, Zhao F, Zhao J. Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update. Expert Opin Pharmacother 2018; 19:795-807. [PMID: 29693454 DOI: 10.1080/14656566.2018.1465928] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment. AREAS COVERED This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects. EXPERT OPINION Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.
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Affiliation(s)
- Heling Zhang
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Guoshuang Shen
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Shuisheng Zhang
- b Department of Medical Oncology , National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Feng Du
- c Peking University Cancer Hospital and Institute , Beijing , China
| | - Yang Cao
- d The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou , China
| | - Jun Jiang
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Fangchao Zheng
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Xinfu Ma
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Ziyi Wang
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Dengfen Ren
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Raees Ahmad
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Fuxin Zhao
- a Affiliated Hospital of Qinghai University , Xining , China
| | - Jiuda Zhao
- a Affiliated Hospital of Qinghai University , Xining , China
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