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Vitale G, Gaudenzi G, Oldani M, Pandozzi C, Filice A, Jaafar S, Barrea L, Colao A, Faggiano A. Nutritional status and gastroenteropancreatic neuroendocrine neoplasms: lights and shadows with a clinical guide from the NIKE Group. Rev Endocr Metab Disord 2025; 26:161-174. [PMID: 39653986 DOI: 10.1007/s11154-024-09937-2] [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] [Accepted: 11/29/2024] [Indexed: 03/19/2025]
Abstract
Neuroendocrine neoplasms (NENs) originating in the gastroenteropancreatic (GEP) tract are rare tumors often associated with significant metabolic disturbances and nutritional challenges. This review explores the intricate relationship between nutritional status and the development, progression, and prognosis of GEP-NENs. Through an extensive literature search encompassing studies up to April 2024, we examined various factors, including obesity, malnutrition, metabolic syndrome and type 2 diabetes mellitus, and their roles in the development and progression of GEP-NENs. The review highlights the dual role of obesity, both as a risk factor and a potential prognostic indicator, drawing attention to the 'obesity paradox' observed in cancer research. Additionally, we discuss the impact of malnutrition on patient outcomes and emphasize the need for comprehensive nutritional assessments beyond BMI. This analysis highlights the importance of incorporating nutritional interventions into preventive and therapeutic strategies for GEP-NEN patients. Future research should further clarify these associations and develop personalized nutritional management protocols to improve patient prognosis and quality of life. Acronyms adopted in the text and tables: AOR: adjusted odd ratio, BIA: Bioelectrical Impedance Analysis, BMI: Body Mass Index, CI: confidence interval, CLARINET: Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumor, FLI: fatty liver index, GEP: gastroenteropancreatic, GLIM: global leadership into malnutrition, HR: hazard ratio, MS: metabolic syndrome, MUST: malabsorption universal screening tool, NEC: neuroendocrine carcinoma, NENs: Neuroendocrine neoplasms, NETs: Neuroendocrine tumors, NRS: Nutritional Risk Screening, OR: odd ratio, OS: overall survival, PFS: progression-free survival, RR: risk ratio, SGA: Subjective Global Assessment, T2DM: type 2 diabetes mellitus, VAI: visceral adiposity index, WD: well-differentiated.
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Affiliation(s)
- Giovanni Vitale
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy.
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
| | - Germano Gaudenzi
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy
| | - Monica Oldani
- Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS, Istituto Auxologico Italiano, Milan, Italy
| | - Carla Pandozzi
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Alessia Filice
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Simona Jaafar
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Luigi Barrea
- Department of Wellbeing, Nutrition and Sport, Pegaso Telematic University, Centro Direzionale Isola F2, Via Porzio, 80143, Naples, Italy
- Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
| | - Annamaria Colao
- Education for Health and Sustainable Development, UNESCO Chair, Federico II University, Naples, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Sapienza University of Rome, Rome, Italy
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Massironi S, Panzuto F, Zilli A, Rinzivillo M, Ciliberto A, Romano E, Danese S, Laviano A. Nutritional aspects in neuroendocrine neoplasms. bridging the gap between dietary interventions and cancer care strategies: a scoping review. J Endocrinol Invest 2025; 48:269-281. [PMID: 39395115 PMCID: PMC11785655 DOI: 10.1007/s40618-024-02462-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 08/26/2024] [Indexed: 10/14/2024]
Abstract
PURPOSE Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients. METHODS We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes. RESULTS Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies. CONCLUSION Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.
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Affiliation(s)
- Sara Massironi
- Division of Gastroenterology Fondazione, IRCCS San Gerardo dei Tintori, Monza, Italia.
- Division of Gastroenterology, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy.
| | - Francesco Panzuto
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Maria Rinzivillo
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Ambra Ciliberto
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Elena Romano
- Department of Surgical-Medical Sciences and Translational Medicine, Digestive Disease Unit, Sapienza University of Rome, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandro Laviano
- Department of Translational and Precision Medicine, Clinical Nutrition Unit, Sapienza University of Rome, Sant'Andrea University Hospital, Rome, Italy
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La Salvia A, Bellino S, Fanciulli G. Streptozotocin in pancreatic neuroendocrine tumors: a focus on efficacy and safety. Expert Opin Pharmacother 2025; 26:115-118. [PMID: 39711000 DOI: 10.1080/14656566.2024.2446618] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 11/02/2024] [Accepted: 12/20/2024] [Indexed: 12/24/2024]
Affiliation(s)
- Anna La Salvia
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
| | - Stefania Bellino
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
| | - Giuseppe Fanciulli
- Neuroendocrine Tumor Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
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Zhang L, Jin Z, Li C, He Z, Zhang B, Chen Q, You J, Ma X, Shen H, Wang F, Wu L, Ma C, Zhang S. An interpretable machine learning model based on contrast-enhanced CT parameters for predicting treatment response to conventional transarterial chemoembolization in patients with hepatocellular carcinoma. LA RADIOLOGIA MEDICA 2024; 129:353-367. [PMID: 38353864 DOI: 10.1007/s11547-024-01785-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 01/10/2024] [Indexed: 03/16/2024]
Abstract
OBJECTIVE To explore the potential of pre-therapy computed tomography (CT) parameters in predicting the treatment response to initial conventional TACE (cTACE) in intermediate-stage hepatocellular carcinoma (HCC) and develop an interpretable machine learning model. METHODS This retrospective study included 367 patients with intermediate-stage HCC who received cTACE as first-line therapy from three centers. We measured the mean attenuation values of target lesions on multi-phase contrast-enhanced CT and further calculated three CT parameters, including arterial (AER), portal venous (PER), and arterial portal venous (APR) enhancement ratios. We used logistic regression analysis to select discriminative features and trained three machine learning models via 5-fold cross-validation. The performance in predicting treatment response was evaluated in terms of discrimination, calibration, and clinical utility. Afterward, a Shapley additive explanation (SHAP) algorithm was leveraged to interpret the outputs of the best-performing model. RESULTS The mean diameter, ECOG performance status, and cirrhosis were the important clinical predictors of cTACE treatment response, by multiple logistic regression. Adding the CT parameters to clinical variables showed significant improvement in performance (net reclassification index, 0.318, P < 0.001). The Random Forest model (hereafter, RF-combined model) integrating CT parameters and clinical variables demonstrated the highest performance on external validation dataset (AUC of 0.800). The decision curve analysis illustrated the optimal clinical benefits of RF-combined model. This model could successfully stratify patients into responders and non-responders with distinct survival (P = 0.001). CONCLUSION The RF-combined model can serve as a robust and interpretable tool to identify the appropriate crowd for cTACE sessions, sparing patients from receiving ineffective and unnecessary treatments.
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Affiliation(s)
- Lu Zhang
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Zhe Jin
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Chen Li
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Zicong He
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Bin Zhang
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Qiuying Chen
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Jingjing You
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Xiao Ma
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Hui Shen
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Fei Wang
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China
| | - Lingeng Wu
- Department of Interventional Therapy, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine Guangzhou, Guangdong, 510627, China.
| | - Cunwen Ma
- Department of Radiology, The People's Hospital of Wenshan Prefecture, No. 228 Kaihua East Road, Wenshan, 663000, Yunnan, China.
| | - Shuixing Zhang
- Department of Radiology, The First Affiliated Hospital of Jinan University, No. 613 Huangpu West Road, Tianhe District, Guangzhou, 510627, Guangdong, China.
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DePietro DM, Li X, Shamimi-Noori SM. Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When? Semin Intervent Radiol 2024; 41:27-47. [PMID: 38495263 PMCID: PMC10940046 DOI: 10.1055/s-0043-1777716] [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: 03/19/2024]
Abstract
Liver metastases are the most common malignancy found in the liver and are 20 to 40 times more common than primary hepatic tumors, including hepatocellular carcinoma. Patients with liver metastases often present with advanced disease and are not eligible for curative-intent surgery or ablative techniques. The unique hepatic arterial blood supply of liver metastases allows interventional radiologists to target these tumors with transarterial therapies. Transarterial chemoembolization (TACE) has been studied in the treatment of liver metastases originating from a variety of primary malignancies and has demonstrated benefits in terms of hepatic progression-free survival, overall survival, and symptomatic relief, among other benefits. Depending on the primary tumor from which they originate, liver metastases may have different indications for TACE, may utilize different TACE regimens and techniques, and may result in different post-procedural outcomes. This review offers an overview of TACE techniques and specific considerations in the treatment of liver metastases, provides an in-depth review of TACE in the treatment of liver metastases originating from colorectal cancer, neuroendocrine tumor, and uveal melanoma, which represent some of the many tumors beyond hepatocellular carcinoma that can be treated by TACE, and summarizes data regarding when one should consider TACE in their treatment algorithms.
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Affiliation(s)
- Daniel M. DePietro
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Xin Li
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Susan M. Shamimi-Noori
- Division of Interventional Radiology, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Zhang J, Zhu H, Shen L, Li J, Zhang X, Bai C, Zhou Z, Yu X, Li Z, Li E, Yuan X, Lou W, Chi Y, Xu N, Yin Y, Bai Y, Zhang T, Xiu D, Chen J, Qin S, Wang X, Yang Y, Shi H, Luo X, Fan S, Su W, Lu M, Xu J. Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib. Chin J Cancer Res 2023; 35:526-535. [PMID: 37969958 PMCID: PMC10643338 DOI: 10.21147/j.issn.1000-9604.2023.05.09] [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: 07/24/2023] [Accepted: 09/15/2023] [Indexed: 11/17/2023] Open
Abstract
Objective Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis. Methods We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models. Results Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs. 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs. 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins. Conclusions These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.
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Affiliation(s)
- Jianwei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Haibin Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jie Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiaoyan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510062, China
| | - Xianrui Yu
- Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
| | - Zhiping Li
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 332001, China
| | - Enxiao Li
- Department of Medical Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Yihebali Chi
- Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Nong Xu
- Department of Medical Oncology, the First Affiliated Hospital of Zhejiang University, Hangzhou 310009, China
| | - Yongmei Yin
- Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China
| | - Tao Zhang
- Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing 100191, China
| | - Jia Chen
- Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing 214206, China
| | - Shukui Qin
- Cancer Center of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing 210016, China
| | - Xiuwen Wang
- Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Yujie Yang
- Department of Clinical and Regulatory Affairs, HUTCHMED Limited, Shanghai 200001, China
| | - Haoyun Shi
- Department of Clinical and Regulatory Affairs, HUTCHMED Limited, Shanghai 200001, China
| | - Xian Luo
- Department of Clinical and Regulatory Affairs, HUTCHMED Limited, Shanghai 200001, China
| | - Songhua Fan
- Department of Clinical and Regulatory Affairs, HUTCHMED Limited, Shanghai 200001, China
| | - Weiguo Su
- Department of Clinical and Regulatory Affairs, HUTCHMED Limited, Shanghai 200001, China
| | - Ming Lu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, the Fifth Medical Center, Chinese PLA General Hospital, Beijing 100071, China
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Fohlen A, Beaudouin R, Alvès A, Bouhier-Leporrier K, Pasik C, Pelage JP. Conventional Transarterial Chemo embolization Using Streptozocin in Patients with Unresectable Neuroendocrine Liver Metastases. Cancers (Basel) 2023; 15:4021. [PMID: 37627049 PMCID: PMC10452304 DOI: 10.3390/cancers15164021] [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: 06/19/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. PATIENTS AND METHODS A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. RESULTS A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84-99%), 84% (CI = 72-95%), 69% (CI = 53-84%) and 63% (C = 46-81%), respectively. CONCLUSIONS cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression.
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Affiliation(s)
- Audrey Fohlen
- Interventional Radiology, Caen University Medical Center, 14033 Caen, France; (A.F.); (R.B.)
- Centre National de la Recherche Scientifique, Imaging & Therapeutic Strategies for Cancer & Brain Tissue UMR 6030 GIP CYCERON “ISTCT-CERVOxy”, Normandie Caen University, 14000 Caen, France
| | - Remi Beaudouin
- Interventional Radiology, Caen University Medical Center, 14033 Caen, France; (A.F.); (R.B.)
| | - Arnaud Alvès
- Department of Digestive Surgery, Caen University Medical Center, 14033 Caen, France;
- Interdisciplinary Research Unit for Cancer Prevention and Treatment “ANTICIPE”, Inserm Unity UMR 1086, Normancy Caen University, Calvados General Tumor Registry, Centre François Baclesse, 14000 Caen, France
| | - Karine Bouhier-Leporrier
- Department of Hepato-Gastroenterology and Digestive Oncology, Caen University Medical Center, 14033 Caen, France;
| | | | - Jean-Pierre Pelage
- Interventional Radiology, Caen University Medical Center, 14033 Caen, France; (A.F.); (R.B.)
- Centre National de la Recherche Scientifique, Imaging & Therapeutic Strategies for Cancer & Brain Tissue UMR 6030 GIP CYCERON “ISTCT-CERVOxy”, Normandie Caen University, 14000 Caen, France
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Victory Srinivasan N, Venugopal S. A Comparison of the Outcomes of Transarterial Chemoembolization and Transarterial Radioembolization in the Management of Neuroendocrine Liver Metastases in Adults: A Systematic Review. Cureus 2023; 15:e40592. [PMID: 37469827 PMCID: PMC10353751 DOI: 10.7759/cureus.40592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 06/17/2023] [Indexed: 07/21/2023] Open
Abstract
The purpose of this article is to review the existing English scientific literature and determine the superior modality between transarterial chemoembolization (TACE) and radioembolization (TARE) in the treatment of neuroendocrine liver metastases (NELMs). To that end, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search PubMed, the Cochrane Library, and Google Scholar. We identified 14 observational studies and no randomized controlled trials (RCTs) investigating the use of TACE or TARE to treat NELM. We used the Newcastle-Ottawa Scale to assess the risk of bias in these studies. We concluded that TACE and TARE appeared to have similar outcomes when comparing overall survival, progression-free survival, radiological response, symptomatic response, and the incidence of severe adverse events. Further large-scale RCTs are needed to identify the superior modality conclusively. We also identified several unique prognostic factors for overall survival, such as the neutrophil-lymphocyte ratio, volumetric multiparametric magnetic resonance imaging, serum albumin, alkaline phosphatase, and pancreastatin.
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Affiliation(s)
| | - Sathish Venugopal
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Exploring the Relationship between Obesity, Metabolic Syndrome and Neuroendocrine Neoplasms. Metabolites 2022; 12:metabo12111150. [DOI: 10.3390/metabo12111150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/13/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Obesity is a major burden for modern medicine, with many links to negative health outcomes, including the increased incidence of certain cancer types. Interestingly, some studies have supported the concept of an “Obesity Paradox”, where some cancer patients living with obesity have been shown to have a better prognosis than non-obese patients. Neuroendocrine neoplasms (NENs) are malignancies originating from neuroendocrine cells, in some cases retaining important functional properties with consequences for metabolism and nutritional status. In this review, we summarize the existing evidence demonstrating that obesity is both a risk factor for developing NENs as well as a good prognostic factor. We further identify the limitations of existing studies and further avenues of research that will be necessary to optimize the metabolic and nutritional status of patients living with NENs to ensure improved outcomes.
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Liu Y, Liu H, Chen W, Yu H, Yao W, Fan W, Li J, Chen M, Chen J, Wang Y. Prolonged progression-free survival achieved by octreotide LAR plus transarterial embolization in low-to-intermediate grade neuroendocrine tumor liver metastases with high hepatic tumor burden. Cancer Med 2022; 11:2588-2600. [PMID: 35289113 PMCID: PMC9249979 DOI: 10.1002/cam4.4628] [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: 09/24/2021] [Revised: 01/06/2022] [Accepted: 01/18/2022] [Indexed: 11/07/2022] Open
Abstract
Objective To evaluate the efficacy and outcome of transarterial embolization (TAE) plus octreotide long‐acting repeatable (LAR) on patients with low‐to‐intermediate neuroendocrine tumor liver metastases (NETLM). Methods One hundred and sixteen patients with G1/G2 NETLM treated with TAE plus octreotide LAR at the First Affiliated Hospital, Sun Yat‐sen University between January 12, 2016 and September 24, 2020 were reviewed. Radiological response was evaluated according to response evaluation criterion in solid tumor version 1.1. Overall progression‐free survival (PFS) was assessed. Intrahepatic and extrahepatic PFS were evaluated in the whole cohort and in patients with the extrahepatic disease (EHD), respectively. Factors affecting treatment response and overall PFS were analyzed using the logistic regression model and Cox proportional hazard model. Adverse events were recorded and evaluated according to Common Terminology Criteria for Adverse Events 5.0. Results The median overall PFS of the whole cohort was 13.6 months. For the patients with EHD, the median intrahepatic PFS and extrahepatic PFS were 13.6 and 26.1 months, respectively. The median overall PFS of patients with hepatic tumor burden (HTB) <10%, 10%–25%, 25%–50%, and >50% were 25.2, 13.6, 11.2, and 12.3 months, respectively. Ki67 >10%, HTB >50%, and bone metastasis were independently associated with overall PFS. The objective response rate was 78.4%. In patients with HTB 25%–50% and >50%, responders (complete response or partial response) had significant prolonged PFS compared with nonresponders (stable disease or progression disease). Ki67 >10%, bone metastasis, and clear tumor margin were independently associated with response to TAE. The most frequent adverse events that occurred after TAE were postembolization syndrome, and no treatment‐associated death occurred during the perioperative period. Conclusion Transarterial embolization plus octreotide LAR can significantly prolong the PFS of neuroendocrine tumor liver metastases, especially with high HTB over 50%. Selected patients with HTB >25% (ki67 ≤10%, absence of bone metastasis, clear tumor margin) could derive prognostic advantage from the combined treatment.
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Affiliation(s)
- Yiming Liu
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Haikuan Liu
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenchuan Chen
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hang Yu
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wang Yao
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiaping Li
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Wang
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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11
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Mouw TJ, Scoggins CR. Radiographic features and behaviors of neuroendocrine tumors: can we judge a book by its cover? Hepatobiliary Surg Nutr 2021; 10:573-574. [PMID: 34430548 DOI: 10.21037/hbsn-21-174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 06/03/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Tyler J Mouw
- Hiram C. Polk, Jr, MD Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
| | - Charles R Scoggins
- Hiram C. Polk, Jr, MD Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA
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12
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Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer. Cancers (Basel) 2021; 13:cancers13143607. [PMID: 34298822 PMCID: PMC8304541 DOI: 10.3390/cancers13143607] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 12/27/2022] Open
Abstract
Simple Summary In the era of precision medicine, novel targets have emerged on the surface of cancer cells, which have been exploited for the purpose of radioligand therapy. However, there have been variations in the way these receptors are expressed, especially in prostate cancers and neuroendocrine tumors. This variable expression of receptors across the grades of cancers led to the concept of ‘target heterogeneity’, which has not just impacted therapeutic decisions but also their outcomes. Radiopharmaceuticals targeting receptors need to be used when there are specific indicators—either clinical, radiological, or at molecular level—warranting their use. In addition, response to these radioligands can be assessed using different techniques, whereby we can prognosticate further outcomes. We shall also discuss, in this review, the conventional as well as novel approaches of detecting heterogeneity in prostate cancers and neuroendocrine tumors. Abstract Tumor or target heterogeneity (TH) implies presence of variable cellular populations having different genomic characteristics within the same tumor, or in different tumor sites of the same patient. The challenge is to identify this heterogeneity, as it has emerged as the most common cause of ‘treatment resistance’, to current therapeutic agents. We have focused our discussion on ‘Prostate Cancer’ and ‘Neuroendocrine Tumors’, and looked at the established methods for demonstrating heterogeneity, each with its advantages and drawbacks. Also, the available theranostic radiotracers targeting PSMA and somatostatin receptors combined with targeted systemic agents, have been described. Lu-177 labeled PSMA and DOTATATE are the ‘standard of care’ radionuclide therapeutic tracers for management of progressive treatment-resistant prostate cancer and NET. These approved therapies have shown reasonable benefit in treatment outcome, with improvement in quality of life parameters. Various biomarkers and predictors of response to radionuclide therapies targeting TH which are currently available and those which can be explored have been elaborated in details. Imaging-based features using artificial intelligence (AI) need to be developed to further predict the presence of TH. Also, novel theranostic tools binding to newer targets on surface of cancer cell should be explored to overcome the treatment resistance to current treatment regimens.
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Artale S, Barzaghi S, Grillo N, Maggi C, Lepori S, Butti C, Bovio A, Barbarini L, Colombo A, Zanlorenzi L, Castiglioni E, Trojani A. Role of Diet in the Management of Carcinoid Syndrome: Clinical Recommendations for Nutrition in Patients with Neuroendocrine Tumors. Nutr Cancer 2020; 74:2-11. [PMID: 33148022 DOI: 10.1080/01635581.2020.1838572] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nutrition and metabolism are altered in patients with gastroenteropancreatic neuroendocrine tumors, which is related to excessive production of gastrointestinal hormones, peptides, and amines that can cause maldigestion, diarrhea, steatorrhea, and altered gastrointestinal motility. Patients with carcinoid syndrome are at risk of malnutrition due to tryptophan depletion, reduced intake of food, and loss of appetite because of diarrhea and/or flushing. To date, there is limited information on the nutritional issues faced by patients with neuroendocrine tumors, and on what specific recommendations should be made to patients concerning nutrition at various stages of the disease process. Dietary planning should therefore be an integral part of multidisciplinary management for patients with neuroendocrine tumors. Herein, we review current guidance for nutrition in patients with neuroendocrine tumors, focusing on intake of amines and foods to avoid, as well as concurrent medications. We also propose a new and practical food pyramid based on the principles of Mediterranean diet 4.0 that can be easily adapted according to the unmet needs of patients with neuroendocrine tumors at all stages of disease. The overarching goal of the present review is to create greater awareness of nutritional care and considerations that should be given to patients with neuroendocrine tumors.
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Affiliation(s)
- Salvatore Artale
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Sabrina Barzaghi
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Nunziata Grillo
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Claudia Maggi
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Stefano Lepori
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Chiara Butti
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Antonella Bovio
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Lucia Barbarini
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Andrea Colombo
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Laura Zanlorenzi
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Elena Castiglioni
- Department of Medical Oncology, Busto Arsizio-Gallarate Hospital, ASST Valle Olona, Gallarate, Italy
| | - Alessandra Trojani
- Divisione di Ematologia, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
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The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review. J Clin Med 2020; 9:jcm9072302. [PMID: 32698459 PMCID: PMC7408651 DOI: 10.3390/jcm9072302] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/08/2020] [Accepted: 07/10/2020] [Indexed: 02/07/2023] Open
Abstract
Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM.
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15
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Interventional Liver-Directed Therapy for Neuroendocrine Metastases: Current Status and Future Directions. Curr Treat Options Oncol 2020; 21:52. [PMID: 32447461 DOI: 10.1007/s11864-020-00751-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OPINION STATEMENT Liver-directed therapy should be considered for patients with unresectable liver metastases from neuroendocrine tumor if symptomatic or progressing despite medical management. Our experience and current literature shows that the bland embolization, chemoembolization, and radioembolization are very effective in controlling symptoms and disease burden in the liver, and that these embolization modalities are similar in terms of efficacy and radiologic response. Their safety profiles differ, however, with recent studies suggesting an increase in biliary toxicity with drug-eluting bead chemoembolization over conventional chemoembolization, and a risk of long-term hepatotoxicity with radioembolization. For this reason, we tailor the type of embolotherapy to each patient according to their clinical status, symptoms, degree of tumor burden, histologic grade, and life expectancy. We do not recommend a "one-size-fits-all" approach. Our general strategy is to use bland embolization as first-line embolotherapy, and radioembolization for patients with high-grade tumors or who have failed other embolotherapy.
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16
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Ma ZY, Gong YF, Zhuang HK, Zhou ZX, Huang SZ, Zou YP, Huang BW, Sun ZH, Zhang CZ, Tang YQ, Hou BH. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26:2305-2322. [PMID: 32476795 PMCID: PMC7243647 DOI: 10.3748/wjg.v26.i19.2305] [Citation(s) in RCA: 112] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/27/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending.
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Affiliation(s)
- Zu-Yi Ma
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Yuan-Feng Gong
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Hong-Kai Zhuang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Zi-Xuan Zhou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Shan-Zhou Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yi-Ping Zou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Bo-Wen Huang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Zhong-Hai Sun
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
- Shantou University of Medical College, Shantou 515000, Guangdong Province, China
| | - Chuan-Zhao Zhang
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
| | - Yun-Qiang Tang
- Department of Hepatobiliary Surgery, the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510080, Guangdong Province, China
| | - Bao-Hua Hou
- Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong Province, China
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Armstrong EA, Beal EW, Shah M, Konda B, Abdel-Misih S, Ejaz A, Dillhoff ME, Pawlik TM, Cloyd JM. Radiographic characteristics of neuroendocrine liver metastases do not predict clinical outcomes following liver resection. Hepatobiliary Surg Nutr 2020; 9:1-12. [PMID: 32140474 DOI: 10.21037/hbsn.2019.06.02] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Previous research has demonstrated that specific radiographic criteria, including the presence of calcifications and the enhancement pattern on computed tomography (CT) imaging, correlates with clinicopathologic features and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (NET). We sought to investigate whether these radiographic characteristics were prognostic among patients with neuroendocrine liver metastases (NELM) undergoing surgical resection. Methods The preoperative contrast-enhanced CT scans of all patients who underwent resection of NELM at a single institution between 2000-2015 were retrospectively reviewed. The presence of calcifications was determined on non-contrast phase imaging. Enhancement on the arterial phase scan was categorized as hyperenhancing, hypoenhancing, or mixed. Relevant clinicopathologic characteristics as well as recurrence-free survival (RFS) and overall survival (OS) were compared between groups. Results Among 82 patients who underwent resection of NELM, 57 had available data on calcifications while 51 had data available on arterial enhancement patterns. Among all patients, median age was 58 (IQR: 47-63) and the majority were female (N=48, 59.5%). The most common primary tumor locations were pancreas (N=25, 30.5%) and small bowel (N=27, 32.9%). The most commonly performed operations were right hepatectomy (N=29, 35.4%), bisegmentectomy (N=15, 18.3%), and segmentectomy (N=14, 17.1%). Median tumor number was 4 (IQR: 2-9), median Ki-67 was 5% (IQR: 2-10%), and median size of the largest liver metastasis was 4.5 (IQR: 2.8-7.7) cm. Twelve (21%) patients had tumor calcifications. Among patients with and without calcifications there were no differences in demographics, clinicopathologic characteristics, RFS (P=0.772) or OS (P=0.095). Arterial enhancement was hypoenhancing in 23 (45.1%), hyperenhancing in 10 (19.6%), and mixed in 18 (35.3%). Similarly, there were no differences between arterial enhancement groups in demographics, clinicopathologic characteristics, RFS (P=0.618) or OS (P=0.268). Conclusions Radiographic characteristics on contrast-enhanced CT are not associated with the outcomes of patients undergoing resection of NELM. Future investigations should evaluate the prognostic impact of functional neuroendocrine imaging.
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Affiliation(s)
| | - Eliza W Beal
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Manisha Shah
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Bhavana Konda
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Sherif Abdel-Misih
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Mary E Dillhoff
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Gulpinar B, Peker E, Soydal C, Araz M, Elhan AH. Can we differentiate histologic subtypes of neuroendocrine tumour liver metastases at a single phase contrast-enhanced CT-correlation with Ga-68 DOTATATE PET/CT findings. Br J Radiol 2020; 93:20190735. [PMID: 31922897 DOI: 10.1259/bjr.20190735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To assess the usefulness of a single-phase contrast-enhanced CT to differentiate subtypes of neuroendocrine tumour (NET) liver metastases and to evaluate the correlation between CT features and Ga-68 DOTATATE positron emission tomography/CT (PET/CT) findings. METHODS Between December 2017 and April 2019 patients with liver metastases of neuroendocrine tumours who underwent CT and Ga-68 DOTATATE PET/CT were enrolled in the study. All patients involved in the study had undergone a standardised single-phase contrast-enhanced CT. Whole body PET/CT images were obtained with a combined PET/CT scanner. All CT images were retrospectively analysed by two radiologists. Enhancement patterns of lesions were assessed. For quantitative examination; CT attenuation values of metastatic lesions, liver parenchyma and aorta were measured using a freehand ROI and tumour-to-liver ratio [T-L = (Tumour-Liver) / Liver] and tumour-to-aorta ratio [T-A = (Tumour-Aorta) / Aorta] were calculated. The lesion with the highest Ga-68 DOTATATE uptake in the liver was used for calculations. The metabolic tumour volume (MTV), maximum standardised uptake value (SUV max) and SUV mean were calculated for the target liver lesion. RESULTS A total of 137 NET liver metastases divided into in three groups: 49 (35.7%) pancreatic, 60 (44.5%) gastroenteric and 26 (18.9%) lung NET liver metastases were analysed. Gastroenteric NET metastases often showed heterogeneous enhancement which was significantly higher than in the pancreas and lung NET liver metastases (p < 0.001). 96.72% (n = 59) of the gastroenteric NET liver metastases were hypoattenuating whereas the most frequent presentation for the pancreatic group was hyperattenuation (63.26%,n = 31). The difference in enhancement patterns of the liver metastases was statistically significant (p < 0.001) with respect to the location of the primary tumour. For quantitative analysis; tumour CT values were significantly different between the groups (p < 0.001). The T-L ratio was statistically different between gastroenteric and pancreatic NET liver metastases and pancreatic and lung NET groups (p < 0.001). The T-A ratio was significantly higher in the pancreatic NET metastases (p < 0.001). SUVmax, SUVmean and MTV values, however, were not significantly different between the subgroups. There was a weak positive correlation between T-L ratio and SUV meanvalues. CONCLUSION We noticed statistically significant differences in both qualitative and quantitative CT features between histologic subgroups of neuroendocrine tumour liver metastases at a single phase contrast-enhanced CT. ADVANCES IN KNOWLEDGE Our study will be the first in the literature which extensively focus on assessing the CT features of liver metastases of NETs at a single phase CT and Ga-68DOTATATE PET/CT. As the different histological subtypes of NET liver metastases exhibit different clinical outcomes, these features might help to identify the primary tumour to provide optimal treatment.
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Affiliation(s)
- Basak Gulpinar
- Department of Radiology, Ankara University School of Medicine, Ankara, Turkey
| | - Elif Peker
- Department of Radiology, Ankara University School of Medicine, Ankara, Turkey
| | - Cigdem Soydal
- Department of NuclearMedicine, Ankara University School of Medicine, Ankara, Turkey
| | - Mine Araz
- Department of NuclearMedicine, Ankara University School of Medicine, Ankara, Turkey
| | - Atilla Halil Elhan
- Department of Biostatistics, Ankara University School of Medicine, Ankara, Turkey
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Liu Y, Chen W, Cui W, Liu H, Zhou X, Chen L, Li J, Chen M, Chen J, Wang Y. Quantitative Pretreatment CT Parameters as Predictors of Tumor Response of Neuroendocrine Tumor Liver Metastasis to Transcatheter Arterial Bland Embolization. Neuroendocrinology 2020; 110:697-704. [PMID: 31639795 DOI: 10.1159/000504257] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 10/21/2019] [Indexed: 12/31/2022]
Abstract
PURPOSE To assess whether parameters on preprocedural CT can be utilized to predict the response of NETLM to transcatheter arterial bland embolization (TAE). METHODS We retrospectively reviewed 135 target lesions from 48 NETLM patients who underwent TAE and with complete preprocedural multiphasic CT. Parameters on preprocedural CT including the longest diameter, mean attenuation value in nonenhanced, arterial, and portal-venous phases were collected from each target lesion. Radiological responses were assessed according to RECIST 1.1. The parameters of responder lesions and nonresponder lesions were compared. Arterial enhancement index (AEI) and portal-venous enhancement index (PEI) were calculated. The predictive function of AEI and PEI on tumor response was analyzed by receiver operating characteristic (ROC) curve. RESULTS A total of 72.6% target lesions had a partial response. For patients, the objective response rate was 72.9%. Mean attenuation values of responder lesions were significantly higher than nonresponder lesions in both arterial and portal-venous phases (105.36 ± 37.24 vs. 76.01 ± 19.19, p < 0.001; 96.61 ± 24.04 vs. 82.12 ± 21.37, p = 0.002). ROC curve showed that both AEI and PEI were effective in predicting tumor response (area under the curve [AUC] 0.757, p < 0.001; AUC 0.655, p = 0.005). CONCLUSION AEI and PEI, parameters from evaluation of CT pretreatment attenuation of NETLMs, could predict response to TAE treatment.
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Affiliation(s)
- Yiming Liu
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenchuan Chen
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wei Cui
- Department of Interventional Therapy, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Haikuan Liu
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiangfei Zhou
- Department of Interventional Radiology, General Hospital of Yongmei Group, Yongcheng, China
| | - Luohai Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiaping Li
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,
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Dermine S, Palmieri LJ, Lavolé J, Barré A, Dohan A, Abou Ali E, Cottereau AS, Gaujoux S, Brezault C, Chaussade S, Coriat R. Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors. J Clin Med 2019; 8:jcm8111907. [PMID: 31703375 PMCID: PMC6912565 DOI: 10.3390/jcm8111907] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 10/29/2019] [Accepted: 11/05/2019] [Indexed: 12/18/2022] Open
Abstract
The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.
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Affiliation(s)
- Solène Dermine
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
| | - Lola-Jade Palmieri
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Julie Lavolé
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Amélie Barré
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Antony Dohan
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Radiology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Anne-Ségolène Cottereau
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Nuclear Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Sébastien Gaujoux
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Digestive Surgery Unit, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Catherine Brezault
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
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Piron L, Cassinotto C, Guiu B. [Interventional radiology of liver tumors]. Presse Med 2019; 48:1156-1168. [PMID: 31672452 DOI: 10.1016/j.lpm.2019.10.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 10/02/2019] [Indexed: 02/08/2023] Open
Abstract
Interventional radiology (IR) has considerably grown since the 90s and has currently a central position in the management of patients suffering from cancer. The aim of this paper is to describe the principle, indications, technique and results of three common hepatic oncologic IR procedures: preoperative portal vein embolization, transarterial chemoembolization and radioembolization. Portal vein embolization is performed before a right hepatectomy in order to increase the left liver volume and functional capacity to ensure adequate liver function of the future remnant liver and to prevent the post-hepatectomy liver failure. It is a proven, well-tolerated and effective technique, allowing most of patients to undergo surgery. Transarterial chemoembolization consists of an injection of a chemotherapeutic agent and an embolic agent into the hepatic artery to locally act on liver tumors. It is the standard of care for BCLC stage B hepatocellular carcinoma and is also recommended for the liver metastases treatment, mainly from neuroendocrine tumors. Radioembolization is an IR procedure on the rise that consists of the injection into the hepatic artery of Yttrium 90 loaded microparticles, which will preferentially deliver high dose on the tumors, sparing the adjacent hepatic parenchyma. Radioembolization is recommended for the palliative treatment of HCC and for colorectal cancer liver metastases resistant to treatment. It is a very well tolerated intervention which place has yet to be defined in the management of neuroendocrine tumors liver metastases and unresectable cholangiocarcinoma. IR is a constantly evolving discipline with proven techniques playing a major role in the oncological management of liver tumor patients. In oncology, IR is now the 4th patient management linchpin alongside oncology, surgery and radiotherapy.
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Affiliation(s)
- Lauranne Piron
- CHU Montpellier, University of Montpellier, Saint-Éloi Hospital, Department of Radiology, Montpellier, France.
| | - Christophe Cassinotto
- CHU Montpellier, University of Montpellier, Saint-Éloi Hospital, Department of Radiology, Montpellier, France
| | - Boris Guiu
- CHU Montpellier, University of Montpellier, Saint-Éloi Hospital, Department of Radiology, Montpellier, France
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Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II study. Eur J Cancer 2019; 123:92-100. [PMID: 31678771 DOI: 10.1016/j.ejca.2019.09.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 09/09/2019] [Accepted: 09/26/2019] [Indexed: 11/24/2022]
Abstract
BACKGROUND Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity. METHODS This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7-30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%. RESULTS Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5-43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14-23), 17 (13-22), and 51 (33-60) months. The most common grade III-IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%). CONCLUSIONS The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease. TRIAL REGISTRATION NCT01678664 (clinicaltrials.gov).
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23
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Liver metastases of neuroendocrine tumors: is it possible to diagnose different histologic subtypes depending on multiphasic CT features? Abdom Radiol (NY) 2019; 44:2147-2155. [PMID: 30863999 DOI: 10.1007/s00261-019-01963-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
PURPOSE To assess and compare the multiphasic computed tomography (CT) features of neuroendocrine tumor (NET) liver metastases and to investigate the possibility to predict the histologic subtype of the primary tumor. MATERIALS AND METHODS Between January 2013 and December 2017 patients with biopsy proven NET with at least one liver metastasis who underwent multiphasic CT were enrolled in this study. All cases were acquired using a standardized multiphasic liver CT protocol, arterial, portal, and hepatic venous phases were obtained. Images were retrospectively analyzed in consensus by two abdominal radiologists blinded to clinical data and histologic subtype. The size, number, and location of lesions were noted. Enhancement patterns of each lesion on arterial, portal, and hepatic venous phases were assessed. For quantitative analysis, CT attenuation of tumors, liver parenchyma, and aorta were measured using a circular region of interest (ROI) on arterial, portal, and hepatic venous phases for reflecting the blood supply of the tumor. Tumor-to-aorta and tumor-to-liver ratio were calculated in all three phases. Differences between subtypes of NET liver metastases were studied using ROC analysis of clustered data. RESULTS A total of 255 neuroendocrine tumor liver metastases divided into 101 (39.6%) pancreatic, 60 (23.5%) gastroenteric and 94 (36.8%) lung NET liver metastases were analyzed. Contrast enhancement of lesions was homogeneous in 78% of patients (n = 199), which was significantly more frequent in patients with pancreatic group than in those with gastroenteric origin (n = 90, 89.1% vs. n = 28, 46.7%; p < 0.001). Gastroenteric NET metastases frequently showed heterogeneous enhancement, which was significantly higher than in the other two groups (50% vs. 3% and 2%). With respect to the location of the primary tumor, the difference in enhancement patterns of the liver lesions was statistically significant (p < 0.001). Pancreatic NET metastases were mostly hyperdense on arterial images and isodense on portal and hepatic venous phase images (79.2%, n = 80). Gastroenteric NET metastases were mostly hyperdense on arterial phase images and hypodense on portal and hepatic venous phase images (n = 28, 46.7%). The most frequent pattern for lung NET metastases was hypoattenuation on all three phase images (n = 44, 46.8%). ROC analysis of clustered data revealed statistically significant differences between pancreatic NET liver metastases, gastroenteric NET liver metastases, and lung NET liver metastases in terms of tumor-to-aorta (T-A) ratio and tumor-to-liver (T-L) ratio (p < 0.001). CONCLUSION We observed statistically significant differences in multiphasic CT features (enhancement pattern, T-A ratio, and T-L ratio) between histologic subtypes of NET liver metastases. As the difference in histological subtypes of NET liver metastases results in a different prognosis and different management strategy, these CT features might help to identify the primary tumor when it is not known to ensure accurate tumor staging and to provide optimal treatment.
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24
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Luo Y, Pandey A, Ghasabeh MA, Pandey P, Varzaneh FN, Zarghampour M, Khoshpouri P, Ameli S, Li Z, Hu D, Kamel IR. Prognostic value of baseline volumetric multiparametric MR imaging in neuroendocrine liver metastases treated with transarterial chemoembolization. Eur Radiol 2019; 29:5160-5171. [DOI: 10.1007/s00330-019-06100-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 01/31/2019] [Accepted: 02/11/2019] [Indexed: 12/17/2022]
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25
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Clement DSVM, Tesselaar MET, van Leerdam ME, Srirajaskanthan R, Ramage JK. Nutritional and vitamin status in patients with neuroendocrine neoplasms. World J Gastroenterol 2019; 25:1171-1184. [PMID: 30886501 PMCID: PMC6421241 DOI: 10.3748/wjg.v25.i10.1171] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/13/2019] [Accepted: 02/22/2019] [Indexed: 02/06/2023] Open
Abstract
Symptoms of gastroenteropancreatic located neuroendocrine neoplasms (GEP-NENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.
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Affiliation(s)
- Dominique SVM Clement
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
| | - Margot ET Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute ENETS Centre of Excellence, Amsterdam 1066 CX, Netherlands
| | - Monique E van Leerdam
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands
| | - Rajaventhan Srirajaskanthan
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
- Department of Gastroenterology, King’s College Hospital, London SE5 9RS, United Kingdom
| | - John K Ramage
- Neuroendocrine Tumour Unit, King’s College Hospital ENETS Centre of Excellence, London SE5 9RS, United Kingdom
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26
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Impact of Nutritional Status on Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) Aggressiveness. Nutrients 2018; 10:nu10121854. [PMID: 30513732 PMCID: PMC6316835 DOI: 10.3390/nu10121854] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 11/14/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023] Open
Abstract
Neuroendocrine tumors (NETs) are rare neoplasms mostly originating from the gastroenteropancreatic tract (GEP-NETs). Data regarding nutritional status in GEP-NET patients are limited. The aim of the study was to investigate the nutritional status and adherence to the Mediterranean Diet (MD) in GEP-NET patients and to correlate them with tumor aggressiveness. A cross-sectional case-control observational study was conducted enrolling 83 patients with well-differentiated G1/G2 GEP-NETs after resection, as well as 83 healthy subjects, age, sex and body mass index-matched. Nutritional status was assessed by evaluating with Bioelectrical Impedance analysis and its phase angle (PhA), adherence to the MD according to PREDIMED score, dietary assessment, anthropometric parameters, and clinico-pathological characteristics. GEP-NET patients consumed less frequently vegetables, fruits, wine, fish/seafood, nuts, and more frequently red/processed meats, butter, cream, margarine, and soda drinks than controls. Patients with more aggressive disease presented a lower adherence to MD according to PREDIMED categories in comparison to G1, localized and free/stable disease status. A smaller PhA value and a lower PREDIMED score were significantly correlated with G2 tumor, metastases, and progressive disease. To the best of our knowledge, this is the first study reporting an association between nutritional status and tumor aggressiveness in a selected group of GEP-NETs. Moreover, higher intakes of food of MD, may represent a potential tool for prevention of tumor aggressiveness. Thus, a skilled nutritionist should be an integral part of the multidisciplinary management of GEP-NET patients.
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Pancreatic Cancer and Obesity: Molecular Mechanisms of Cell Transformation and Chemoresistance. Int J Mol Sci 2018; 19:ijms19113331. [PMID: 30366466 PMCID: PMC6274743 DOI: 10.3390/ijms19113331] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 09/27/2018] [Accepted: 10/22/2018] [Indexed: 12/14/2022] Open
Abstract
Cancer and obesity are the two major epidemics of the 21st century. Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of death, with a five-year overall survival rate of only 8%. Its incidence and mortality have increased in recent years, and this cancer type is expected to be among the top five leading causes of cancer-related death by 2030 in the United States (US). In the last three decades, the prevalence of overweight people has boosted with a consequent increase in obesity-related diseases. Considerable epidemiologic evidence correlates overweight and obese conditions to an increased risk of several types of cancer, including PDAC. Besides being a risk factor for multiple metabolic disorders, the tumor-promoting effects of obesity occur at the local level via inflammatory mediators that are associated with adipose inflammation and metabolic or hormones mediators and microbiota dysbiosis. Although an excess of body mass index (BMI) represents the second most modifiable risk factor for PDAC with an increased cancer related-death of more than 20–40%, still little is known about the molecular mechanisms that underlie this strong association. In this review, we focused on the role of obesity as a preventable risk factor of PDAC, discussing the molecular mechanisms linking obesity to cancer initiation and progression. Moreover, we highlighted the role of obesity in defining chemoresistance, showing how a high BMI can actually reduce response to chemotherapy.
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28
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Cornelis FH, Solomon SB. Treatment of Primary Liver Tumors and Liver Metastases, Part 2: Non-Nuclear Medicine Techniques. J Nucl Med 2018; 59:1801-1808. [PMID: 30361378 DOI: 10.2967/jnumed.116.186379] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 10/19/2018] [Indexed: 02/07/2023] Open
Abstract
Image-guided procedures are used worldwide in the management of primary liver tumors and liver metastases. These locoregional therapies include local tumor ablation and transarterial therapies and can occasionally downstage an inoperable patient to an operable status. In hepatocellular carcinoma, data have suggested that for tumors smaller than 2 cm ablation may be preferable to surgery. Similar results are emerging for colorectal cancer liver metastases. Catheter-directed therapies such as bland embolization, transarterial chemoembolization, and drug-eluting beads represent potential techniques that can provide survival benefit for inoperable patients. In this review we highlight the most used techniques and the evidence supporting their current indications for the treatment of liver tumors. We briefly review upcoming developments in combination strategies with temperature-sensitive liposomes or immunotherapy for enhancing ablation efficacy.
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Affiliation(s)
- Francois H Cornelis
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.,Sorbonne Université, Department of Radiology, Tenon Hospital, Paris, France
| | - Stephen B Solomon
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and
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29
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Altieri B, Barrea L, Modica R, Muscogiuri G, Savastano S, Colao A, Faggiano A. Nutrition and neuroendocrine tumors: An update of the literature. Rev Endocr Metab Disord 2018; 19:159-167. [PMID: 30267297 DOI: 10.1007/s11154-018-9466-z] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with worldwide increasing incidence, high prevalence and survival. Both the tumor itself and the systemic therapy may have an impact on patients' nutrition. Malnutrition negatively impacts on outcome in NETs patients. Moreover, it has been demonstrated that body mass index was a risk factor for NET development and that metabolic syndrome was associated with worse prognosis in these patients. Of note, food could also interact with the metabolism of oral target therapy and antineoplastic agents used for the treatment of progressive NETs. Therefore, the nutritional assessment, based on body composition, and lifestyle modifications should be an integral component of management of the NET patients. The nutrition care plans are an integral part of the multidisciplinary management team for patients with NETs. Nutritionists with expertise in NETs can provide dietary approaches to improve the quality of life and nutritional status during various therapeutic modalities used in patients with NETs. The aim of this review is to critically discuss the importance of nutrition and body composition in patients with NETs.
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Affiliation(s)
- Barbara Altieri
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Wuerzburg, Germany
| | - Luigi Barrea
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
| | - Roberta Modica
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
| | - Giovanna Muscogiuri
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
| | - Silvia Savastano
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy
| | - Antongiulio Faggiano
- Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini 5, 82121, Naples, Italy.
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Borre M, Dam GA, Knudsen AW, Grønbaek H. Nutritional status and nutritional risk in patients with neuroendocrine tumors. Scand J Gastroenterol 2018; 53:284-292. [PMID: 29373941 DOI: 10.1080/00365521.2018.1430848] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Malnutrition is frequent among patients with malignancies and associated with impaired function, reduced quality of life and increased mortality. Few data are available in patients with neuroendocrine tumors (NET) on nutritional status, nutritional risk, and nutrition impact symptoms (NIS). We aimed to assess nutritional status (NS) and risk, level of function and associations with NIS in NET patients. METHODS In a cross-sectional study of NET patients, we measured body mass index (BMI) and handgrip strength (HGS) as markers of NS and muscle function assessed by HGS. The nutritional risk score (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). RESULTS We included 186 patients (51% women), median age 66 years. We observed low BMI (<20.5 kg/m2) in 12%, low HGS in 25%, and impaired level of function in 43% of the patients. About 38% were at nutritional risk, more frequent in patients with residual disease (45% versus 29%, p < .05). Both low HGS, impaired level of function and being at nutritional risk were associated with the NIS: Nausea, vomiting, stomach ache and dry mouth (p < .05) whereas poor appetite and early satiety were only associated with being at nutritional risk and having impaired level of function (p < .05, all). CONCLUSIONS Almost 40% of NET patients were at nutritional risk; and 25% had impaired HGS associated with specific NIS that preclude food intake. We recommend that NET outpatients are screened with NRS-2002 and that HGS and NIS are determined if NET patients need nutritional therapy.
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Affiliation(s)
- Mette Borre
- a Department of Hepatology and Gastroenterology , Aarhus University Hospital ENETS Centre of Excellence, Aarhus University Hospital , Aarhus , Denmark
| | - Gitte Aarøe Dam
- a Department of Hepatology and Gastroenterology , Aarhus University Hospital ENETS Centre of Excellence, Aarhus University Hospital , Aarhus , Denmark
| | - Anne Wilkens Knudsen
- b Medical Division, and Medical Unit, Nutritional Division , Copenhagen University Hospital Hvidovre , Hvidovre , Denmark
| | - Henning Grønbaek
- a Department of Hepatology and Gastroenterology , Aarhus University Hospital ENETS Centre of Excellence, Aarhus University Hospital , Aarhus , Denmark
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de Mestier L, Zappa M, Hentic O, Vilgrain V, Ruszniewski P. Liver transarterial embolizations in metastatic neuroendocrine tumors. Rev Endocr Metab Disord 2017; 18:459-471. [PMID: 28975561 DOI: 10.1007/s11154-017-9431-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The management of patients with well-differentiated neuroendocrine tumors (NET) and non-resectable liver metastases is challenging. Liver-directed transarterial embolization (TAE), transarterial chemo-embolization (TACE) and selective internal radiation therapy (SIRT) have a place of choice among other treatment modalities. However, their utilization relies on a low level of proof, due to the lack of prospective data, the absence of comparative studies and considerable heterogeneity between local practices. TAE and TACE generally achieve average symptomatic, biological and radiological responses of 75%, 56% and 50%, with progression-free survival of 12-18 months, with acceptable tolerance. Although not clearly demonstrated, TACE may be more effective than TAE in pancreatic NET, but not in small-intestine NET. SIRT has been developed more recently and may achieve similar results, with improved tolerance, but decreased cost-effectiveness, although no prospective comparison has been published to date. There is currently no strong argument to choose between TAE, TACE and SIRT, and they have not been compared to other treatment modalities. The evaluation of their efficacy has mostly relied on criteria based on size variations, which do not take into account tumor viability and metabolism, and thus may not be relevant. These techniques may be especially effective when performed as first-line therapies, in patients with non-major liver involvement (<75%) and with hypervascular metastases. Finally, studies exploring their combination with systemic therapies are ongoing.
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Affiliation(s)
- Louis de Mestier
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France.
| | - Magaly Zappa
- Department of Radiology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, Clichy, France
| | - Olivia Hentic
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, Clichy, France
| | - Philippe Ruszniewski
- Department of Gastroenterology and Pancreatology, DHU UNITY, ENETS Center of Excellence, Beaujon Hospital (APHP), Paris-Diderot University, 100 boulevard du Général Leclerc, 92110, Clichy, France
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Sposito C, Droz Dit Busset M, Citterio D, Bongini M, Mazzaferro V. The place of liver transplantation in the treatment of hepatic metastases from neuroendocrine tumors: Pros and cons. Rev Endocr Metab Disord 2017; 18:473-483. [PMID: 29359266 DOI: 10.1007/s11154-017-9439-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome differences for available treatments, due to the long course of disease, surgery for MNETs remains the most effective option in terms of survival and symptom control. Since MNETs frequently present as an oligo-metastatic, liver-limited disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as a potential curative treatment. Nevertheless, experience with LT for MNETs is limited and burdened by highly heterogeneous outcomes and significant recurrence rate, mostly explained by the variability of selection criteria. Several prognostic factors have been identified: extended surgery on primary tumor associated to LT, elderly patients, pancreatic primary (pNET), extensive liver involvement, poorly differentiated tumors, high Ki67 levels and short wait time to LT. A proper patients' selection based on these data (Milan NET criteria) allows a significant survival advantage over non-transplant strategies, with excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best option for selected patients with MNETs. The use of organs for MNETs is therefore justified.
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Affiliation(s)
- Carlo Sposito
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Michele Droz Dit Busset
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Davide Citterio
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Marco Bongini
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori (National Cancer Institute), Via Venezian 1, 20133, Milan, Italy.
- University of Milan, Milan, Italy.
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Gallo M, Muscogiuri G, Pizza G, Ruggeri RM, Barrea L, Faggiano A, Colao A. The management of neuroendocrine tumours: A nutritional viewpoint. Crit Rev Food Sci Nutr 2017; 59:1046-1057. [PMID: 29020456 DOI: 10.1080/10408398.2017.1390729] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nutritional status in patients with neuroendocrine tumours (NETs), especially of gastroenteropancreatic origin, can be deeply affected by excessive production of gastrointestinal hormones, peptides, and amines, which can lead to malabsorption, diarrhoea, steatorrhea, and altered gastrointestinal motility. Besides, the surgical and/or medical management of NETs can lead to alteration of gastrointestinal secretory, motor, and absorptive functions, with both dietary and nutritional consequences. Indeed, disease-related malnutrition is a frequently encountered yet both underrecognized and understudied clinical phenomenon in patients with NETs, with substantial prognostic and socioeconomic consequences. Most of these conditions can be alleviated by a tailored nutritional approach, also with the aim of improving the efficacy of cancer treatments. In this setting, skilled nutritionists can play a fundamental role in the multidisciplinary health care team in NETs management and their presence should be recommended. The aim of this review is to provide dietary advices for each specific condition in patients with NETs, underlining the importance of a nutritional approach to treat malnutrition in this setting. Further, we will provide preliminary evidence coming from our data on the assessment of nutritional status in a single cohort of patients with NETs.
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Affiliation(s)
- Marco Gallo
- a Oncological Endocrinology Unit, Department of Medical Sciences , University of Turin , AOU Città della Salute e della Scienza di Torino, Turin , Italy
| | | | - Genoveffa Pizza
- c Unit of Internal Medicine, Landolfi Hospital , Solofra , Avellino , Italy
| | - Rosaria Maddalena Ruggeri
- d Department of Clinical and Experimental Medicine , Unit of Endocrinology, University of Messina , Messina , Italy
| | - Luigi Barrea
- b Ios and Coleman Medicina Futura Medical Centre , Naples , Italy
| | - Antongiulio Faggiano
- e Department of Clinical Medicine and Surgery , University "Federico II" of Naples , Naples , Italy
| | - Annamaria Colao
- e Department of Clinical Medicine and Surgery , University "Federico II" of Naples , Naples , Italy
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Ronot M, Cuccioli F, Dioguardi Burgio M, Vullierme MP, Hentic O, Ruszniewski P, d’Assignies G, Vilgrain V. Neuroendocrine liver metastases: Vascular patterns on triple-phase MDCT are indicative of primary tumour location. Eur J Radiol 2017; 89:156-162. [DOI: 10.1016/j.ejrad.2017.02.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 01/25/2017] [Accepted: 02/04/2017] [Indexed: 10/20/2022]
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Maasberg S, Knappe-Drzikova B, Vonderbeck D, Jann H, Weylandt KH, Grieser C, Pascher A, Schefold JC, Pavel M, Wiedenmann B, Sturm A, Pape UF. Malnutrition Predicts Clinical Outcome in Patients with Neuroendocrine Neoplasia. Neuroendocrinology 2017; 104:11-25. [PMID: 26641457 DOI: 10.1159/000442983] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 11/30/2015] [Indexed: 12/16/2022]
Abstract
Malnutrition is a common problem in oncological diseases, influencing treatment outcomes, treatment complications, quality of life and survival. The potential role of malnutrition has not yet been studied systematically in neuroendocrine neoplasms (NEN), which, due to their growing prevalence and additional therapeutic options, provide an increasing clinical challenge to diagnosis and management. The aim of this cross-sectional observational study, which included a long-term follow-up, was therefore to define the prevalence of malnutrition in 203 patients with NEN using various methodological approaches, and to analyse the short- and long-term outcome of malnourished patients. A detailed subgroup analysis was also performed to define risk factors for poorer outcome. When applying malnutrition screening scores, 21-25% of the NEN patients were at risk of or demonstrated manifest malnutrition. This was confirmed by anthropometric measurements, by determination of serum surrogate parameters such as albumin as well as by bioelectrical impedance analysis (BIA), particularly phase angle α. The length of hospital stay was significantly longer in malnourished NEN patients, while long-term overall survival was highly significantly reduced. Patients with high-grade (G3) neuroendocrine carcinomas, progressive disease and undergoing chemotherapy were at particular risk of malnutrition associated with a poorer outcome. Multivariate analysis confirmed the important and highly significant role of malnutrition as an independent prognostic factor for NEN besides proliferative capacity (G3 NEC). Malnutrition is therefore an underrecognized problem in NEN patients which should systematically be diagnosed by widely available standard methods such as Nutritional Risk Screening (NRS), serum albumin assessment and BIA, and treated to improve both short- and long-term outcomes.
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Affiliation(s)
- Sebastian Maasberg
- Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Pelage JP, Fohlen A, Mitry E, Lagrange C, Beauchet A, Rougier P. Chemoembolization of Neuroendocrine Liver Metastases Using Streptozocin and Tris-acryl Microspheres: Embozar (EMBOsphere + ZAnosaR) Study. Cardiovasc Intervent Radiol 2016; 40:394-400. [PMID: 28035432 DOI: 10.1007/s00270-016-1535-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 12/08/2016] [Indexed: 11/30/2022]
Abstract
PURPOSE The purpose of this prospective observational study was to evaluate the efficacy and tolerability of transarterial chemoembolization (TACE) for neuroendocrine liver metastases using a combination of streptozocin, Lipiodol, and tris-acryl microspheres. PATIENTS AND METHODS A total of 16 men and 9 women aged 59.6 ± 11.3 years, all with predominant liver disease, underwent 54 courses of TACE using an emulsion of 1.5 g of streptozocin and 10 ml of Lipiodol. Additional embolization was performed using 300-500 µm tris-acryl microspheres. Morphological response was evaluated using the RECIST criteria on multi-detector computed tomography or MRI. Clinical efficacy was evaluated particularly in patients with carcinoid syndrome. RESULTS The primary tumor was located in the small bowel or pancreas in 21 (84%) patients. Eleven (44%) patients presented with a carcinoid syndrome. Nineteen (76%) patients presented with more than 10 liver nodules. One delayed case of ischemic cholecystitis was treated conservatively. After a median follow-up of 36.1 months, 1 (4%) patient had a complete response, 12 (48%) patients had a partial response, and 7 (28%) patients had a stable disease corresponding to a disease control rate of 80%. All patients with carcinoid syndrome had significant improvement. Median time to progression was 18.8 months and overall survival was 100, 100, and 92% at 1, 2, and 3 years, respectively. Seven patients presented with extrahepatic progression with abdominal lymphadenopathies or metastases to the brain, ovary, adrenal gland, or lung. CONCLUSION Optimized TACE using a combination of streptozocin, Lipiodol, and tris-acryl microspheres is effective and well tolerated.
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Affiliation(s)
- Jean-Pierre Pelage
- Department of Diagnostic Imaging and Interventional Radiology, Caen University and Medical Center, Avenue Cote de Nacre, 14033, Caen Cedex 9, France. .,CERVOxy, CEA, CNRS, ISTCT - Imagerie et Stratégie Thérapeutiques des Pathologies Cérébrales et Tumorales (M Bernaudin), Université de Basse-Normandie UNICAEN, Caen, France.
| | - Audrey Fohlen
- Department of Diagnostic Imaging and Interventional Radiology, Caen University and Medical Center, Avenue Cote de Nacre, 14033, Caen Cedex 9, France.,CERVOxy, CEA, CNRS, ISTCT - Imagerie et Stratégie Thérapeutiques des Pathologies Cérébrales et Tumorales (M Bernaudin), Université de Basse-Normandie UNICAEN, Caen, France
| | - Emmanuel Mitry
- Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France
| | - Christine Lagrange
- Department of Radiology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France
| | - Alain Beauchet
- Department of Biostatistics and Public Health, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France
| | - Philippe Rougier
- Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France
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Dromain C, Déandréis D, Scoazec JY, Goere D, Ducreux M, Baudin E, Tselikas L. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging 2016; 97:1241-1257. [PMID: 27876341 DOI: 10.1016/j.diii.2016.07.012] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 07/18/2016] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.
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Affiliation(s)
- C Dromain
- Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland.
| | - D Déandréis
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - J-Y Scoazec
- Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - D Goere
- Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - M Ducreux
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - E Baudin
- Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - L Tselikas
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
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Abstract
Neuroendocrine tumors are increasingly diagnosed, either incidentally as part of screening processes, or for symptoms, which have commonly been mistaken for other disorders initially. The diagnostic workup to characterize tumor behaviour and prognosis focuses on histologic, anatomic, and functional imaging assessments. Several therapeutic options exist for patients ranging from curative and debulking surgery through to liver-directed therapies and systemic treatments. Multimodal therapies are often required over the patient's disease history. The management paradigm can be complex but should be focused on curative resections and then on controlling symptoms and limiting disease progression. There are several new systemic therapies that have completed phase 3 studies with new compounds being studied in phase 2. Genetic and epigenetic markers may lead to a new era of personalised therapy in the future.
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Affiliation(s)
- Ron Basuroy
- Neuroendocrine Tumour Unit, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS, UK
| | - Raj Srirajaskanthan
- Neuroendocrine Tumour Unit, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS, UK
| | - John K Ramage
- Neuroendocrine Tumour Unit, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London SE5 9RS, UK.
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Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion. Cardiovasc Intervent Radiol 2015; 39:334-43. [PMID: 26390875 DOI: 10.1007/s00270-015-1208-y] [Citation(s) in RCA: 199] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 08/25/2015] [Indexed: 12/12/2022]
Abstract
Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .
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de Baere T, Deschamps F, Tselikas L, Ducreux M, Planchard D, Pearson E, Berdelou A, Leboulleux S, Elias D, Baudin E. GEP-NETS update: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur J Endocrinol 2015; 172:R151-66. [PMID: 25385817 DOI: 10.1530/eje-14-0630] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.
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Affiliation(s)
- Thierry de Baere
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Frederic Deschamps
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Lambros Tselikas
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Michel Ducreux
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - David Planchard
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Ernesto Pearson
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Amandine Berdelou
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Sophie Leboulleux
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Dominique Elias
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
| | - Eric Baudin
- Interventional RadiologyMedical OncologyNuclear Medicine and Endocrine OncologyOncology SurgeryEndocrinologyInstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, FranceUniversité Paris-SudLe Kremlin Bicêtre, France
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Clancy TE. Liver-directed therapy for neuroendocrine liver metastases. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.14.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract: Neuroendocrine tumors are relatively uncommon neoplasms presenting with a wide spectrum of clinical behavior. Many patients may present with or develop liver metastases from neuroendocrine tumors, which significantly influences prognosis and the potential for symptoms. Data suggest that some patients may have symptomatic relief and oncologic benefit from liver-directed therapy for neuroendocrine tumor metastases. Surgical resection, tumor ablation, transarterial therapy such as bland embolization, chemoembolization and radioembolization, as well as liver transplantation have been studied as liver-directed therapies. Data continue to emerge to help guide selection of treatment modality for an individual patient. The spectrum of behavior of neuroendocrine metastases and heterogeneity in the literature are a challenge to arriving at cohesive recommendations for all patients.
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Baudin E, Caron P, Lombard-Bohas C, Tabarin A, Mitry E, Reznick Y, Taieb D, Pattou F, Goudet P, Vezzosi D, Scoazec JY, Cadiot G, Borson-Chazot F, Do Cao C. [Malignant insulinoma: recommendations for workup and treatment]. Presse Med 2014; 43:645-59. [PMID: 24857257 DOI: 10.1016/j.lpm.2013.08.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 07/15/2013] [Accepted: 08/19/2013] [Indexed: 02/09/2023] Open
Abstract
Insulinoma are malignant in 4 to 14 % of cases. Their rarity and the sparse data available in the literature have limited publication of specific guidelines for their management. The following review aim to provide up-to-date recommendations on initial evaluation including pathologic grading, measures to control hypoglycemia, antitumor strategies and long term follow-up. Will be discussed in detail respective indications of surgery, diazoxide, somatostatin analogs, everolimus, sunitinib, liver directed treatments including arterial embolization, chemotherapy and radiometabolic therapy. A Medline search using terms "insulinoma", "neuroendocrine pancreatic tumors", "islet cell carcinoma", "malignant insulinoma" was performed limiting the selection to English language articles and adult age cases, along with cross referencing.
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Affiliation(s)
- Eric Baudin
- Institut Gustave-Roussy, service de médecine nucléaire et d'oncologie endocrinienne, 94805 Villejuif cedex, France.
| | - Philippe Caron
- CHU Rangueil-Larrey, pôle cardiovasculaire et métabolique, service d'endocrinologie et maladies métaboliques, 31059 Toulouse cedex 9, France
| | | | - Antoine Tabarin
- Hôpital Haut-Lévêque, service d'endocrinologie, 33600 Pessac, France
| | - Emmanuel Mitry
- Institut Curie, hôpital René-Huguenin, service d'onco-gastroentérologie, 92210 Saint-Cloud, France
| | - Yves Reznick
- CHU Côte-de-Nacre, unité fonctionnelle d'endocrinologie et maladies métaboliques, 14033 Caen cedex, France
| | - David Taieb
- CHU de la Timone, service central de biophysique et de médecine nucléaire, 13005 Marseille, France
| | - François Pattou
- Hôpital Claude-Huriez, service de chirurgie endocrinienne, 59000 Lille, France
| | - Pierre Goudet
- CHU de Dijon, service de chirurgie générale et endocrinienne, 21000 Dijon, France
| | - Delphine Vezzosi
- CHU Rangueil-Larrey, pôle cardiovasculaire et métabolique, service d'endocrinologie et maladies métaboliques, 31059 Toulouse cedex 9, France
| | - Jean-Yves Scoazec
- Institut Gustave-Roussy, service de biologie et de pathologie médicales, 94805 Villejuif cedex, France
| | - Guillaume Cadiot
- Hôpital Robert-Debré, service d'hépato-gastro-entérologie et de cancérologie digestive, 51100 Reims, France
| | - Françoise Borson-Chazot
- Hospices Civils de Lyon, Fédération d'endocrinologie du pole Est, Fédération d'endocrinologie et centre de médecine nucléaire, 69500 Lyon, France
| | - Christine Do Cao
- Hôpital Claude-Huriez, service d'endocrinologie et de maladies métaboliques, 59000 Lille, France
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Quelles stratégies dans le traitement des tumeurs neuroendocrines digestives ? ONCOLOGIE 2013. [DOI: 10.1007/s10269-013-2331-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Shrikhande SV, Sirohi B, Goel M, Barreto SG. Pancreatic neuroendocrine tumors. Indian J Gastroenterol 2013; 32:3-17. [PMID: 23054950 DOI: 10.1007/s12664-012-0257-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 09/04/2012] [Indexed: 02/04/2023]
Abstract
Pancreatic neuroendocrine tumors (pancreatic NETs) are rare, low- to intermediate-grade neoplasms thought to arise from the pancreatic islets. Recent advances in pathology and our understanding of the biological behavior of this group of tumors has resulted in changes in their nomenclature and how we treat them. This review puts into perspective our current understanding of pancreatic NETs in terms of their incidence, pathology, and management.
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Affiliation(s)
- Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, India.
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Rossi RE, Massironi S, Spampatti MP, Conte D, Ciafardini C, Cavalcoli F, Peracchi M. Treatment of liver metastases in patients with digestive neuroendocrine tumors. J Gastrointest Surg 2012; 16:1981-1992. [PMID: 22829240 DOI: 10.1007/s11605-012-1951-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 06/24/2012] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver metastases are a strong prognostic indicator in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Therapeutic options for metastatic NETs are expanding and not mutually exclusive. AIMS This paper reviews the literature relating to multidisciplinary approach towards GEP-NET metastases, to highlight advances in knowledge regarding these tumors, and to understand the interdisciplinary management of individual patients. METHODS A PubMed search was performed for English-language publications from 1995 through 2012. Reference lists from studies selected were manually searched to identify further relevant reports. Manuscripts comparing different therapeutic options and advances for GEP-NET-related liver metastases were selected. RESULTS There is considerable controversy regarding the optimal management of GEP-NET metastases. Although radical surgery still remains the gold standard, a variety of other therapeutic options are available for metastatic GEP-NETs, including loco-regional chemotherapy/radiotherapy, radioembolization, systemic peptide receptor radionuclide therapy, biotherapy, and chemotherapy. In selected patients, liver transplantation should also be considered. Systemic somatostatin analogues and/or interferon show anti-proliferative effects, representing an appropriate first-line treatment for most patients. In advanced metastatic NETs, recent options include targeted therapies (i.e., everolimus and sunitinib). CONCLUSIONS It is evident that multidisciplinary care and multimodality treatments remain the cornerstone of management of NET patients. Since NETs often show a more indolent behavior compared to other malignancies, physicians should aim to preserve a satisfactory quality of life for the patient by personalizing the therapeutic approach according to the tumor's features and prognostic factors.
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Affiliation(s)
- Roberta Elisa Rossi
- Postgraduate School of Gastroenterology, Università degli Studi di Milano, Milan, Italy.
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Overview of neuroendocrine liver metastases treatment. EJC Suppl 2012. [DOI: 10.1016/s1359-6349(12)70048-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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John BJ, Davidson BR. Treatment options for unresectable neuroendocrine liver metastases. Expert Rev Gastroenterol Hepatol 2012; 6:357-69. [PMID: 22646257 DOI: 10.1586/egh.11.60] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatic metastases develop in 85% of patients with gastroenteropancreatic neuroendocrine tumors. Radical surgery, which involves resection of the primary and liver metastases, is the mainstay of treatment, with 60-70% 5-year survival and 35% 10-year survival rates. However, less than 15% of neuroendocrine tumor liver metastases (NETLMs) are resectable, owing either to multifocality or the inability to preserve sufficient parenchyma following resection. This article deals with the therapeutic modalities available for nonresectable liver metastases, and the therapeutic options available for management of nonresectable NETLMs are discussed. Targeted therapies for NETLMs include hepatic artery embolization, transcatheter arterial chemoembolization, radiolabeled/drug-eluting microspheres, radiofrequency ablation, cryoablation and phenol injection. Hepatic artery embolization/transcatheter arterial chemoembolization is associated with 75-100% symptom relief and an objective tumor response varying from 33 to 80%. Other modalities, such as biotherapy, peptide receptor therapy and chemotherapy, target both the primary and metastatic disease. Their effects on NETLMs as a subgroup have not been evaluated. Various therapeutic options are available for the treatment of unresectable NETLMs. Most offer significant symptomatic relief, with only a few comparative studies showing survival benefit. Most of the available evidence is based on retrospective and prospective case series rather than randomized controlled trials. Well-designed studies on existing treatment modalities and the search for newer therapeutic options are required.
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Affiliation(s)
- Biku Joseph John
- HPB and Liver Transplant Surgery and Neuroendocrine Unit, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
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Zappa M, Abdel-Rehim M, Hentic O, Vullierme MP, Ruszniewski P, Vilgrain V. Liver-directed therapies in liver metastases from neuroendocrine tumors of the gastrointestinal tract. Target Oncol 2012; 7:107-16. [PMID: 22707276 DOI: 10.1007/s11523-012-0219-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 05/02/2012] [Indexed: 01/31/2023]
Abstract
Presence of liver metastases in neuroendocrine tumors is a major factor altering both quality of life and prognosis. Surgery is recognized as the sole curative treatment. When it is not possible, radiological directed therapies are crucial, particularly in liver metastases from the small bowel. Thermal ablative therapies as radiofrequency ablation and microwave are alternative treatments alone or in combination with surgery. Hepatic artery embolization or chemoembolization, as radioembolization, has been shown to have good clinical, biochemical, and morphological responses when liver burden does not permit ablative therapies. However, technical issues are multiple and there is no randomized study to compare their efficacy. The choice of management depends on liver burden and metastases pattern, but also on origin of the primary tumor, tumor differentiation, and tumor proliferative activity. These patients should benefit of a multidisciplinary management to limit morbidity and mortality.
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Affiliation(s)
- Magaly Zappa
- Department of Radiology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, 100, boulevard du général Leclerc, 92110, Clichy, France.
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Guiu B, Deschamps F, Aho S, Munck F, Dromain C, Boige V, Malka D, Leboulleux S, Ducreux M, Schlumberger M, Baudin E, de Baere T. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 2012; 56:609-17. [PMID: 22027582 DOI: 10.1016/j.jhep.2011.09.012] [Citation(s) in RCA: 135] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Revised: 09/01/2011] [Accepted: 09/06/2011] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Transarterial chemoembolisation (TACE) is usually performed by injecting an emulsion of a drug and iodised oil. Drug-eluting beads (DEBs) have undeniable pharmacological advantages by offering simultaneous embolisation and sustained release of the drug to the tumour. No data are currently available on liver/biliary injury following DEB-TACE. This study describes and compares liver/biliary injuries encountered with TACE in tumours developed in cirrhotic (hepatocellular carcinoma (HCC)) and non-cirrhotic (endocrine tumours (NETs)) livers. METHODS In consecutive patients treated for a well-differentiated metastatic NET (n=120) or a HCC (n=88), 684 CT- and MR-scans were analysed. Liver/biliary injuries were classified as follows: dilated bile duct, portal vein narrowing, portal venous thrombosis and biloma/liver infarct. A generalised estimating equation logistic regression model was used. RESULTS A liver/biliary injury followed 17.2% (82/476) of sessions in 30.8% (64/208) of patients. The occurrence of liver/biliary injury was associated with DEB-TACE (OR=6.63; p<0.001) irrespectively of the tumour type. Biloma/parenchymal infarct was strongly associated with both DEB-TACE (OR=9.78; p=0.002) and NETs (OR: 8.13; p=0.04). Biloma/liver infarcts were managed conservatively but were associated with an increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatases, and gamma glutamyl transpeptidase (p=0.005, p=0.005, p=0.012, and p=0.006, respectively). CONCLUSIONS Liver/biliary injuries are independently associated with DEB-TACE. Biloma/liver infarct, the most serious injury, is independently associated with both DEB-TACE and NETs. The absence of such an association in TACE of HCC may be explained by the hypertrophied peribiliary plexus observed in cirrhosis, which protects against the ischemic/chemical insult of bile ducts. We suggest caution when using DEB-TACE in the non-cirrhotic liver.
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Affiliation(s)
- Boris Guiu
- Department of Interventional Radiology, Institut Gustave Roussy, Villejuif, France.
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Gu P, Wu J, Newman E, Muggia F. Treatment of liver metastases in patients with neuroendocrine tumors of gastroesophageal and pancreatic origin. Int J Hepatol 2012; 2012:131659. [PMID: 22518318 PMCID: PMC3299245 DOI: 10.1155/2012/131659] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Revised: 11/16/2011] [Accepted: 12/04/2011] [Indexed: 12/23/2022] Open
Abstract
Well-to-moderately differentiated neuroendocrine tumors of gastroesophageal and pancreatic origin (GEP-NETs) with liver metastasis are a heterogeneous group of malignancies for which a range of therapeutic options have been employed. Surgical resection of hepatic metastases or hepatic artery embolization may be beneficial in patients with hepatic-predominant metastatic disease. Patients with "carcinoid" syndrome and syndromes associated with functional pancreatic NET (PNET) can be effectively treated with somatostatin analogs. On the other hand, the efficacy of systemic chemotherapy for these patients is limited. A placebo-controlled, double-blind, prospective, and randomized study showed that octreotide LAR improves progression-free survival in patients with advanced midgut functional "carcinoids." In patients with advanced pancreatic NET, randomized, placebo-controlled studies have recently demonstrated that treatment with the tyrosine kinase inhibitor sunitinib or with mTOR inhibitor everolimus is associated with improved progression-free survival. Based on these studies, octreotide LAR, sunitinib, or everolimus are now considered as first-line therapeutic options in patients with advanced NET. Future studies will likely further define the role of these agents in patients with carcinoid liver metastasis and pancreatic NET liver metastasis.
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Affiliation(s)
- Ping Gu
- Department of Hematology and Medical Oncology, NYU Cancer Institute, New York, NY 10016, USA
| | - Jennifer Wu
- Department of Hematology and Medical Oncology, NYU Cancer Institute, New York, NY 10016, USA
| | - Elliot Newman
- Department of General Surgery, NYU Medical Center New York, NY 10016, USA
| | - Franco Muggia
- Department of Medical Oncology, NYU Cancer Institute, New York, NY 10016, USA
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