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Virarkar M, Aziz A, Sun J, Morani AC, Frumovitz M, Bhosale P. Impact of metastasis site on overall survival in neuroendocrine cervical carcinoma. Abdom Radiol (NY) 2025; 50:2703-2709. [PMID: 39592479 DOI: 10.1007/s00261-024-04716-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 11/28/2024]
Affiliation(s)
| | | | - Jia Sun
- The University of Texas MD Anderson Cancer Center, Houston, USA
| | | | | | - Priya Bhosale
- The University of Texas MD Anderson Cancer Center, Houston, USA
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2
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Modica R, Benevento E, Altieri B, Minotta R, Liccardi A, Cannavale G, Di Iasi G, Colao A. Role of Bone Metastases in Lung Neuroendocrine Neoplasms: Clinical Presentation, Treatment and Impact on Prognosis. Int J Mol Sci 2024; 25:8957. [PMID: 39201642 PMCID: PMC11354689 DOI: 10.3390/ijms25168957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 09/02/2024] Open
Abstract
Lung neuroendocrine neoplasms (L-NEN) are heterogeneous tumors. While bone metastases (BM) have been associated with worse prognosis in other NEN, their role in L-NEN deserves in-depth analysis. This study analyzes the clinical presentation, treatment and survival outcomes of L-NEN, focusing on patients with BM compared with patients without metastases or with metastases in other sites (OtherMtx). The clinicopathological and survival data of L-NEN admitted to the Federico II University were retrospectively evaluated. Fifty L-NEN were included. Among 27 metastatic patients (54%), 13 (26%) had BM, more commonly occurring in males than females and in primary bilateral L-NEN or L-NEN > 26 mm, with higher Ki67. Atypical carcinoid and hypovitaminosis D were associated with BM. The number of metastatic sites was higher in patients with BM than OtherMtx. Synchronous metastases were associated with shorter overall survival (OS). The median progression-free survival (PFS) and OS in patients with BM were similar to OtherMtx, but a two-times increased risk of shorter OS was detected. BM do not impact PFS or OS more than OtherMtx, but the increased risk of shorter OS in patients with BM should be considered. Periodic bone evaluation in L-NEN should be recommended.
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Affiliation(s)
- Roberta Modica
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Elio Benevento
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Barbara Altieri
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, 97080 Würzburg, Germany;
| | - Roberto Minotta
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Alessia Liccardi
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Giuseppe Cannavale
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Gianfranco Di Iasi
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
| | - Annamaria Colao
- Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy; (E.B.); (R.M.); (A.L.); (G.C.); (G.D.I.); (A.C.)
- UNESCO Chair “Education for Health and Sustainable Development”, Federico II University, 80131 Naples, Italy
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Yu G, Liu S, Wang Z, Liu Q, Ren H, Hu W. Palliative primary tumor resection may not offer survival benefits for patients with unresectable metastatic colorectal neuroendocrine neoplasms, one multicenter retrospective cohort study. BMC Surg 2024; 24:85. [PMID: 38475759 DOI: 10.1186/s12893-024-02380-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 03/04/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND The efficacy of palliative primary tumor resection (PTR) in improving prognosis for patients with unresectable metastatic colorectal neuroendocrine neoplasms (NENs) has not been fully explored. METHODS We performed one retrospective cohort study and recruited 68 patients with unresectable metastatic colorectal NENs from two Chinese medical centers between 2000 and 2022. All patients were assigned to PTR group and no PTR group. The clinicopathological manifestation data were carefully collected, and the survival outcomes were compared between the two groups using Kaplan-Meier methods. Propensity score matching (PSM) was conducted to minimize confounding bias. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS A total of 32 patients received PTR, and the other 36 patients did not. The median progression-free survival (PFS) and overall survival (OS) times were 4 and 22 months in the whole cohort, respectively. For patients who received no PTR, the median OS was 16 months, and the 1-year OS rate and 3-year OS rate were 56.4% and 39.6%, respectively. For patients who received PTR, the median OS was 24 months, and the 1-year OS rate and 3-year OS rate were 67.9% and 34.1%, respectively. However, the Kaplan-Meier survival curves and log-rank test demonstrated no significant survival difference between the two groups (P = 0.963). Moreover, palliative PTR was also not confirmed as a prognostic factor in subsequent univariable and multivariable Cox proportional hazards regression analyses in both the original and matched cohorts. Only histological differentiation was identified as an independent prognostic factor affecting PFS [hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.02-3.41, P = 0.043] and OS [HR = 3.70, 95% CI: 1.09-12.48, P = 0.035] in the original cohort. CONCLUSIONS Palliative PTR may not offer survival benefits for patients with unresectable metastatic colorectal NENs.
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Affiliation(s)
- Guozhi Yu
- Department of Colorectal and Anal Surgery, Beijing Erlonglu Hospital, Beijing, 100016, China
| | - Shen Liu
- Department of Colorectal Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Zhijie Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Qian Liu
- Department of Colorectal Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Hongchang Ren
- Department of General Surgery, Strategic Support Force Medical Center, No.9, Anxiang North, Desheng Gate, Chaoyang District, Beijing, 100101, China.
| | - Wenhui Hu
- Department of Colorectal Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
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Kroepfl V, Bellotti R, Gasser E, Esswein K, Esser H, Kafka-Ritsch R, Öfner D, Perathoner A. Small bowel neuroendocrine tumors: An analysis of clinical presentation, diagnostic workup and surgical approach—A single center retrospective study. Front Surg 2023; 10:1072435. [PMID: 37077861 PMCID: PMC10106623 DOI: 10.3389/fsurg.2023.1072435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 03/13/2023] [Indexed: 04/05/2023] Open
Abstract
BackgroundNeurocrine neoplasms (NEN) of the small bowel (SBNEN) are a rare entity and mostly asymptomatic. The aim of this study was to explore trends in the clinical presentation, diagnostic workup, surgical approach and oncological outcome in patients with SBNEN at our surgical department.Materials and methodsAll patients who underwent surgical resection for SBNEN from 2004 to 2020 at our department were enrolled in this single center retrospective study.ResultsA total of 32 patients were included in this study. In most cases, the diagnosis was based on incidental findings during endoscopy or radiographic imaging (n = 23; 72%). Twenty cases had a G1 tumor and 12 cases a G2 tumor. The 1-, 3- and 5-year overall survival (OS) were 96%, 86% and 81%, respectively. Patients with a tumor more than 30 mm had a significantly lower OS (p = 0.01). For G1 tumors, the estimated disease-free survival (DFS) was 109 months. Again, the DFS was significantly lower when the tumor had more than 30 mm in diameter (p = 0.013).ConclusionDue to the mostly asymptomatic presentation, the diagnostic workup can be difficult. An aggressive approach and a strict follow-up seem to be important for the oncological outcome.
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Minczeles NS, de Herder WW, Feelders RA, Verburg FA, Hofland J, Brabander T. Long-Term Outcomes of Submaximal Activities of Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients. J Nucl Med 2023; 64:40-46. [PMID: 35680417 DOI: 10.2967/jnumed.122.263856] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 05/25/2022] [Accepted: 05/25/2022] [Indexed: 01/13/2023] Open
Abstract
In the literature, up to 45% of neuroendocrine tumor (NET) patients who are treated with 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) do not receive the intended cumulative activity of 29.6 GBq (800 mCi). The aim of this study was to analyze the efficacy of submaximal activities of PRRT in patients who discontinued treatment for non-disease-related reasons. Methods: We retrospectively included patients with well-differentiated and advanced NETs who underwent PRRT from 2000 until 2019 and did not receive 29.6 GBq of 177Lu-DOTATATE. For comparison, we selected control NET patients who received the intended cumulative activity of 29.6 GBq of 177Lu-DOTATATE between 2000 and 2012. Primary outcomes were progression-free survival (PFS) and tumor response, and the secondary outcome was overall survival (OS). Results: In total, 243 patients received 3.7-27.8 GBq. In 130 patients, the submaximal activity was unrelated to disease (e.g., bone marrow and renal toxicity in 48% and maximal renal absorbed dose in 23%), and they were included. Patients receiving a reduced activity had more bone metastases, a lower body mass index and albumin level, a higher alkaline phosphatase level, and fewer grade 1 tumors than the 350 patients included in the control group. The disease control rate in the reduced-activity group was 85%, compared with 93% for the control group (P = 0.011). The median PFS (95% CI) was 23 mo (range, 21-26 mo) for the reduced-activity group and 31 mo (range, 27-35 mo) for the control group (P = 0.001), and the median OS (95% CI) was 34 mo (range, 28-40 mo) and 60 mo (range, 53-67 mo), respectively (P < 0.0001). With adjustment for relevant confounders in the multivariable Cox regression analyses, cumulative activity was an independent predictor of both PFS and OS. Conclusion: In NET patients treated with a cumulative activity of less than 29.6 GBq of 177Lu-DOTATATE, PRRT was less efficacious in tumor response and survival than in patients who received 29.6 GBq.
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Affiliation(s)
- Noémie S Minczeles
- Section of Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands; and .,Department of Radiology and Nuclear Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands
| | - Wouter W de Herder
- Section of Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands; and
| | - Richard A Feelders
- Section of Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands; and
| | - Frederik A Verburg
- Department of Radiology and Nuclear Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands
| | - Johannes Hofland
- Section of Endocrinology, Department of Internal Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands; and
| | - Tessa Brabander
- Department of Radiology and Nuclear Medicine, ENETS Centre of Excellence Rotterdam, Erasmus MC and Erasmus MC Cancer Centre, Rotterdam, The Netherlands
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Usefulness of partial splenic embolization for left-sided portal hypertension in a patient with a pancreatic neuroendocrine neoplasm: a case report and review of the literature. Clin J Gastroenterol 2022; 15:796-802. [PMID: 35430638 PMCID: PMC9334412 DOI: 10.1007/s12328-022-01631-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 03/30/2022] [Indexed: 11/01/2022]
Abstract
AbstractLeft-side portal hypertension (LSPH) is caused by isolated obstruction of the splenic vein and is associated with esophagogastric varices that extend from the lower esophagus to the greater curvature of the gastric body. Here, we report on a 74-year-old man with a pancreatic neuroendocrine neoplasm (NEN) in the pancreatic tail with multiple liver metastases. We decided that partial splenic embolization (PSE) was the best course of treatment to prevent rupture of the gastric varices, which were classified as markedly enlarged, nodular, or tumor-shaped and showed erosion of the mucosa. After PSE, the patient had no major complications and was discharged. At 3 and 6 months after the procedure, esophagogastroduodenoscopy and enhanced computerized tomography showed that the gastric varices had improved. This case demonstrates the usefulness of PSE for LSPH in patients with unresected pancreatic NEN.
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Ma L, Wang Y, Teng Y. Decision-Making Behaviour Evolution Among Pork Supply and Demand Subjects Under Normalisation of COVID-19 Prevention and Control: A Case Study in China. Front Public Health 2022; 10:784668. [PMID: 35372239 PMCID: PMC8968786 DOI: 10.3389/fpubh.2022.784668] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 02/09/2022] [Indexed: 11/28/2022] Open
Abstract
Affected by the coronavirus disease 2019 (COVID-19), there were short-term uncertainties in China's live pig industry supply chain. Due to the insufficient supply of pork, the price of pork rose from 33.21 yuan/kg at the end of 2019 to 37.46 yuan/kg in mid-February and fell to 26.41 yuan/kg in mid-May. To restore pig supply and stabilise prices, China issued relevant policies. Given the current effective control of COVID-19 in China, this paper constructed an evolutionary game model of China's pork supply and demand stakeholders under normalisation of COVID-19 prevention and control, analysed the behavioural strategies of consumers, government, and pig farmers, used MATLAB software for data simulation, and expounded on the evolution path and the characteristic rule of tripartite decision-making behaviours. The results showed that government supervision costs, evaluation of government by consumers and pig farmers, government subsidies to pig farmers and consumers, and the proportion of stakeholder behaviours affected the formation of tripartite relationships. The results provide a useful reference for the government to formulate effective policies, increase pig supply, and stabilise pork prices.
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Affiliation(s)
- Li Ma
- College of Engineering, Northeast Agricultural University, Harbin, China
| | - Yidi Wang
- College of Engineering, Northeast Agricultural University, Harbin, China
| | - Yun Teng
- College of Engineering, Northeast Agricultural University, Harbin, China
- Postdoctoral Research Station of Agriculture and Forestry Economics and Management, Northeast Agricultural University, Harbin, China
- *Correspondence: Yun Teng
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Bian XK, Guo JL, Xu SX, Han YW, Lee SC, Zhao JZ. Hexavalent chromium induces centrosome amplification through ROS-ATF6-PLK4 pathway in colon cancer cells. Cell Biol Int 2022; 46:1128-1136. [PMID: 35293662 DOI: 10.1002/cbin.11791] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/25/2022] [Accepted: 03/13/2022] [Indexed: 11/11/2022]
Abstract
Centrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study we investigated how chromium triggers CA. Our results showed that a sub-toxic concentration of chromium induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N-acetyl-L-cysteine (NAC) inhibited chromium-induced activation of ATF6 and upregulation of PLK4. ATF6-specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium-induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS-ATF6-PLK4 pathway and provides molecular targets for inhibiting chromium-mediated CA, which may be useful for the assessment of CA in chromium-promoted tumorigenesis and cancer cell metastasis. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Xue Kai Bian
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
| | - Jia Li Guo
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
| | - Si Xian Xu
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
| | - Ya Wen Han
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
| | - Shao Chin Lee
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
| | - Ji Zhong Zhao
- Institute of Biomedical Sciences and School of Life Sciences, Jiangsu Normal University, Jiangsu, 221112, PR China
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Treatment patterns and oncological outcome of patients with advanced small intestinal neuroendocrine tumors: real-world data from the Medical University of Vienna. Ther Adv Med Oncol 2022; 14:17588359221138389. [DOI: 10.1177/17588359221138389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 10/24/2022] [Indexed: 11/21/2022] Open
Abstract
Background: Different oncological therapies have been approved for small intestinal neuroendocrine tumors (SI-NETs), but relatively little is known about efficacy and long-term outcome outside of phase III trials. Methods: This retrospective analysis assessed patients with well-differentiated, metastatic SI-NETs treated at the Medical University of Vienna, an approved European Neuroendocrine Tumor Society (ENETS) Center of Excellence for neuroendocrine tumors. The primary objective was to assess progression-free survival (PFS) following approved therapies, that is, octreotide, lanreotide, peptide receptor radionuclide therapy (PRRT), and everolimus, in a representative real-world collective. Results: A total of 77 patients receiving systemic treatment for advanced SI-NETs between 2010 and 2021 were included, with a median follow-up time of 82.3 months [95% confidence interval (CI), 57.8–106.8 months]. In the entire collective, the estimated median PFS following first-line therapy was 32.0 months (95% CI, 23.5–40.5 months). Peritoneal carcinomatosis was significantly associated with worse PFS ( p = 0.016). Regarding therapeutic strategies and outcome, 59 patients received somatostatin analogs first line and no significant difference in PFS was observed between lanreotide and octreotide (29.3 versus 35.5 months, p = 0.768). Across all treatment lines, 42 patients underwent PRRT (estimated median PFS: 32.0 months; 95% CI, 25.6–38.3 months) and a small subgroup of 7 patients received everolimus (estimated median PFS: 9.2 months; 95% CI, 1.6–17.0 months). For the total cohort, the estimated median OS following first-line therapy was 100.6 months (95% CI, 82.3–118.8 months), but the high proportion of deaths attributed to NET (77.8%) underlines the lethal nature of the disease. No unexpected toxicities were observed. Conclusions: While peritoneal carcinomatosis emerged as an adverse prognostic factor for PFS in this collective, the long-term outcome of patients treated at a specialized NET center using approved therapies appeared comparable to pivotal studies in SI-NET.
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Maurer E, Heinzel-Gutenbrunner M, Rinke A, Rütz J, Holzer K, Figiel J, Luster M, Bartsch DK. Relevant prognostic factors in patients with stage IV small intestine neuroendocrine neoplasms. J Neuroendocrinol 2022; 34:e13076. [PMID: 34964186 DOI: 10.1111/jne.13076] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 10/10/2021] [Accepted: 11/30/2021] [Indexed: 12/13/2022]
Abstract
There are few, but controversial data on the prognostic role of upfront primary tumour resection and mesenteric lymph node dissection (PTR) in patients with diffuse metastatic small intestinal neuroendocrine neoplasia (SI-NEN). Therefore, the prognostic role of PTR and other factors was determined in this setting. This retrospective cohort study included patients with stage IV SI-NETs with unresectable distant metastases without clinical and radiological signs of acute bowel obstruction or ischaemia. Patients diagnosed from January 2002 to May 2020 were retrieved from a prospective SI-NEN database. Disease specific overall survival (OS) was analysed with regard to upfront PTR and a variety of other clinical (e.g., gender, age, Hedinger disease, carcinoid syndrome, diarrhoea, laboratory parameters, metastatic liver burden, extrahepatic and extra-abdominal metastasis) and pathological (e.g., grading, mesenteric gathering) parameters by uni- and multivariate analysis. A total of 138 patients (60 females, 43.5%) with a median age of 60 years, of whom 101 (73%) underwent PTR and 37 (27%) did not, were included in the analysis. Median OS was 106 (95% CI: 72.52-139.48) months in the PTR group and 52 (95% CI: 30.55-73.46) in the non-PTR group (p = 0.024), but the non-PTR group had more advanced metastatic disease (metastatic liver burden ≥50% 32.4% vs. 13.9%). There was no significant difference between groups regarding the rate of surgery for bowel complications during a median follow-up of 51 months (PTR group 10.9% and non-PTR group 16.2%, p = 0.403). Multivariate analysis revealed age < 60 years, normal C-reactive protein (CRP) at baseline, absence of diarrhoea, less than 50% of metastatic liver burden, and treatment with PRRT as independent positive prognostic factors, whereas PTR showed a strong tendency towards better OS, but level of significance was missed (p = 0.067). However, patients who underwent both, PTR and peptide radioreceptor therapy (PRRT) had the best survival compared to the rest (137 vs. 73 months, p = 0.013). PTR in combination with PRRT significantly prolongs survival in patients with stage IV SI-NEN. Prophylactic PTR does also not result in a lower reoperation rate compared to the non-PTR approach regarding bowel complications.
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Affiliation(s)
- Elisabeth Maurer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | | | - Anja Rinke
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Johannes Rütz
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
| | - Jens Figiel
- Department of Diagnostic and Interventional Radiology, Philipps-University Marburg, Marburg, Germany
| | - Markus Luster
- Department of Nuclear Medicine, Philipps-University Marburg, Marburg, Germany
| | - Detlef Klaus Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery, Philipps-University Marburg, Marburg, Germany
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Van Den Heede K, Chidambaram S, Van Slycke S, Brusselaers N, Warfvinge CF, Ohlsson H, Nordenström E, Almquist M. Effect of primary tumour resection without curative intent in patients with metastatic neuroendocrine tumours of the small intestine and right colon: meta-analysis. Br J Surg 2021; 109:191-199. [DOI: 10.1093/bjs/znab413] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 10/31/2021] [Indexed: 12/13/2022]
Abstract
Abstract
Background
Patients with small intestinal neuroendocrine tumours (siNETs) usually present with advanced disease. Primary tumour resection without curative intent is controversial in patients with metastatic siNETs. The aim of this meta-analysis was to investigate survival after primary tumour resection without curative intent compared with no resection in patients with metastatic siNETs.
Methods
A systematic literature search was performed, using MEDLINE® (PubMed), Embase®, Web of Science, and the Cochrane Library up to 25 February 2021. Studies were included if survival after primary tumour resection versus no resection in patients with metastatic siNETs was reported. Results were pooled in a random-effects meta-analysis, and are reported as hazard ratios (HRs) with 95 per cent confidence intervals. Sensitivity analyses were undertaken to enable comment on the impact of important confounders.
Results
After screening 3659 abstracts, 16 studies, published between 1992 and 2021, met the inclusion criteria, with a total of 9428 patients. Thirteen studies reported HRs adjusted for important confounders and were included in the meta-analysis. Median overall survival was 112 (i.q.r. 82–134) months in the primary tumour resection group compared with 60 (74–88) months in the group without resection. Five-year overall survival rates were 74 (i.q.r. 67–77) and 44 (34–45) per cent respectively. Primary tumour resection was associated with improved survival compared with no resection (HR 0.55, 95 per cent c.i. 0.47 to 0.66). This effect remained in sensitivity analyses.
Conclusion
Primary tumour resection is associated with increased survival in patients with advanced, metastatic siNETs, even after adjusting for important confounders.
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Affiliation(s)
- Klaas Van Den Heede
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of General and Endocrine Surgery, OLV Clinic Aalst, Aalst, Belgium
| | - Swathikan Chidambaram
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Endocrine Surgery, Hammersmith Hospital, London, UK
| | - Sam Van Slycke
- Department of General and Endocrine Surgery, OLV Clinic Aalst, Aalst, Belgium
- Department of Head and Skin, University Hospital Ghent, Ghent, Belgium
- Department of General Surgery, AZ Damiaan, Ostend, Belgium
| | - Nele Brusselaers
- Centre for Translational Microbiome Research Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden
- Department of Family Medicine and Population Health, Global Health Institute, University of Antwerp, Wilrijk, Belgium
| | - Carl Fredrik Warfvinge
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Oncology and Pathology, Lund University, Lund, Sweden
| | - Håkan Ohlsson
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Surgery, Ystad Hospital, Ystad, Sweden
| | - Erik Nordenström
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Martin Almquist
- Department of Surgery, Skåne University Hospital, Lund, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
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12
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Shaib WL, Zakka K, Penley M, Jiang R, Akce M, Wu C, Maithel SK, Sarmiento JM, Kooby D, Behera M, Alese OB, El-Rayes BF. Role of Resection of the Primary in Metastatic Well-Differentiated Neuroendocrine Tumors. Pancreas 2021; 50:1382-1391. [PMID: 35041337 PMCID: PMC10848811 DOI: 10.1097/mpa.0000000000001936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Resection of the primary (RP) in metastatic neuroendocrine tumor (NET) is controversial. The aim was to evaluate survival outcomes for RP in metastatic NET patients. METHODS Data were obtained from US hospitals at the National Cancer Database between 2004 and 2014. χ2, analysis of variance tests, univariate, and multivariate cox proportional hazards models were evaluated. Kaplan-Meier curves and log-rank tests conducted to compare the survival difference of patient characteristics. RESULTS A total of 2361 patients were identified. The mean age was 62.1 years (standard deviation, 13 years), male-to-female ratio 1:1; 33% were small intestine, 26.3% pancreas, and 24.4% lung; 69.6% were well-differentiated; and 42.5% underwent RP. The 5-year overall survival (OS) was significantly improved for patients who underwent RP in small intestine (5-year OS, 63.9% vs 44.2%), lung (5-year OS, 65.4% vs 20.2%), and pancreas tumors (5-year OS, 75.6% vs 30.6%). On multivariate analysis, RP (hazard ratio, 0.46; 95% confidence interval, 0.29-0.73; P < 0.001), female, year of diagnosis 2010-2014, margin, Charlson-Deyo score less than 2, and age less than 51 years, were associated with better OS. CONCLUSIONS Resection of the primary in metastatic well-differentiated NET is associated with improved OS compared with no RP.
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Affiliation(s)
- Walid L. Shaib
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Katerina Zakka
- Department of Internal Medicine, Wellstar Atlanta Medical Center, Atlanta, GA
| | - McKenna Penley
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Renjian Jiang
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Mehmet Akce
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Christina Wu
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Shishir K. Maithel
- Department of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | | | - David Kooby
- Department of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Madhusmita Behera
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
- Winship Research Informatics, Emory University, Atlanta, GA
| | - Olatunji B. Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
| | - Bassel F. El-Rayes
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA
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13
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Resection of Primary Gastrointestinal Neuroendocrine Tumor Among Patients with Non-Resected Metastases Is Associated with Improved Survival: A SEER-Medicare Analysis. J Gastrointest Surg 2021; 25:2368-2376. [PMID: 33403563 DOI: 10.1007/s11605-020-04898-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 12/19/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND The objective of this study was to analyze whether primary tumor resection (PTR) among patients with stage IV gastrointestinal neuroendocrine tumor (GI-NET) and unresected metastases was associated with improved outcomes. METHODS Patients diagnosed with stage IV GI-NETs were identified in the linked SEER-Medicare database from 2004 to 2015. Overall survival (OS) of patients who did versus did not undergo PTR was examined using bivariate and multivariable cox regression analysis as well as propensity score matching (PSM). RESULTS Among 2219 patients with metastatic GI-NETs, 632 (28.5%) underwent PTR, whereas 1587 (71.5%) did not. The majority of individuals had a NET in the pancreas (n = 969, 43.6%); the most common site of metastatic disease was the liver (n = 1064, 47.9%). Patients with stage IV small intestinal NETs most frequently underwent PTR (62.6%) followed by individuals with colon NETs (56.5%). After adjusting for all competing factors, PTR remained independently associated with improved OS (HR = 0.65, 95% CI: 0.56-0.76). Following PSM (n = 236 per group), patients who underwent PTR had improved OS (median OS: 1.3 years vs 0.8 years, p = 0.016). While PTR of NETs originating from stomach, small intestine, colon, and pancreas was associated with improved OS, PTR of rectal NET did not yield a survival benefit. CONCLUSION Primary GI-NET resection was associated with a survival benefit among individuals presenting with metastatic GI-NET with unresected metastases. Resection of primary GI-NET among patients with stage IV disease and unresected metastases should only be performed in selected cases following multi-disciplinary evaluation.
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Stankard M, Soule E, Matteo J. Inferior Vena Cava Syndrome as a Manifestation of Metastatic Carcinoid Tumor. Gastrointest Tumors 2021; 8:138-143. [PMID: 34307313 DOI: 10.1159/000514113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/29/2020] [Indexed: 11/19/2022] Open
Abstract
Small bowel-origin carcinoid tumor is indolent but may metastasize relentlessly to various sites, including the liver. Over the past 9 years, we have treated a 69-year-old woman who has undergone 5 percutaneous liver ablations, 5 hepatic intra-arterial chemoembolizations, an ovarian cryoablation, and a trans-ventral hernia mesenteric cryoablation. These interventions are all related to her inoperable carcinoid malignancy. After the patient presented with swelling of the abdomen and both lower extremities, computed tomography (CT) angiography was performed, revealing a circumferential hepatic metastatic mass encasing the intrahepatic inferior vena cava (IVC) and extensive third spacing of fluids specific to the IVC distribution below the diaphragm. A venogram of the intrahepatic IVC revealed extrinsic compression causing 95% narrowing of the vessel. A balloon was advanced to the level of the lesion and inflated, increasing the caliber of the vessel. Subsequently, 2 covered aortic stent graft cuffs were deployed in an overlapping fashion within the lumen of the IVC, traversing the area of narrowing. Next, an open-cell aortic dissection stent was placed across both overlapping aortic stents from the renal veins to the hepatic veins. Following this, three 17-gauge cryoablation probes were inserted into the segment 1 intrahepatic lesions encasing the newly stented IVC via an anterior percutaneous approach. Two 10-min freeze cycles were performed with intraoperative CT imaging, demonstrating circumferential coverage of the lesions. Posttreatment venogram revealed patent stent grafts within the intrahepatic IVC, and restoration of vessel patency. No immediate postoperative complications were noted. The patient's abdominal and lower extremity swelling resolved completely within 1 week after procedure. Two-month follow-up CT demonstrated markedly decreased size of the metastatic lesions and no adverse effects. Six- and 9-month PET-CT scans demonstrated maintained patency of the IVC stent. This palliative procedure allowed the patient to maintain good performance status and alleviated her symptoms of IVC syndrome. The radial force generated by the multiple aortic stents will ostensibly maintain the patency of the intrahepatic IVC. Cryoablation of the encasing metastatic lesion was performed with markedly decreased size of the tumor on the 2-month follow-up.
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Affiliation(s)
- Matthew Stankard
- Department of Radiology, Florida Atlantic University College of Medicine, Boca Raton, Florida, USA
| | - Erik Soule
- Department of Interventional Radiology, UF Health Jacksonville, University of Florida, Jacksonville, Florida, USA
| | - Jerry Matteo
- Department of Interventional Radiology, UF Health Jacksonville, University of Florida, Jacksonville, Florida, USA
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15
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Rinzivillo M, De Felice I, Magi L, Annibale B, Panzuto F. Octreotide long-acting release (LAR) in combination with other therapies for treatment of neuroendocrine neoplasia: a systematic review. J Gastrointest Oncol 2021; 12:845-855. [PMID: 34012671 PMCID: PMC8107603 DOI: 10.21037/jgo-20-292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 12/07/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND In the last decades, the incidence of neuroendocrine neoplasia (NEN) increased from 1 to 5 new diagnoses/100,000 persons/year. The synthetic somatostatin analogues (SSAs) represent the first-choice treatment for both functionally active and inactive gastro-enteric-pancreatic NEN. This systematic review examines the role of octreotide long-acting release (LAR) in combination with other therapies for NEN management. METHODS Primary outcomes were the disease control rate and the progression free survival (PFS), defined as the time between treatment initiation and progression of disease. Secondary outcomes were overall survival (OS) and safety. RESULTS This systematic review identified 13 studies, concerning the use of octreotide LAR in association with other therapies in advanced NENs and included 1,206 patients. Patients were treated with octreotide LAR in combination with other drugs, mainly with everolimus (404 patients, 35%), but even with Peptide Receptor Radionuclide Therapy, bevacizumab, interferon or fluoride-derivatives. Disease control was observed in 85% cases with SSAs in combination with other therapies; PFS ranged from 15 to 16.4 months and OS from 25 to 61.9 months. SSAs are very well tolerated drugs, with few side effects which are usually mild, not requiring drug withdrawn. CONCLUSIONS The review summarizes the effectiveness and available safety data on octreotide LAR in combination with other therapies in patients with NEN and may provide suggestions to address the therapeutic strategy. Further comparative head-to-head studies are needed to understand which is the best combination treatment for patients with progressive NEN after failure of first-line therapy.
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Affiliation(s)
- Maria Rinzivillo
- Digestive Disease Unit, Sant’ Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Ilaria De Felice
- Digestive Disease Unit, Sant’ Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Ludovica Magi
- Digestive Disease Unit, Sant’ Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, Sant’ Andrea University Hospital, Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, ENETS Center of Excellence, Rome, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant’ Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
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Tran CG, Sherman SK, Howe JR. The Landmark Series: Management of Small Bowel Neuroendocrine Tumors. Ann Surg Oncol 2021; 28:2741-2751. [PMID: 33452604 DOI: 10.1245/s10434-020-09566-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 12/20/2020] [Indexed: 12/12/2022]
Abstract
Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.
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Affiliation(s)
- Catherine G Tran
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Scott K Sherman
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - James R Howe
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
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17
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Cives M, Pellè E, Rinzivillo M, Prosperi D, Tucci M, Silvestris F, Panzuto F. Bone Metastases in Neuroendocrine Tumors: Molecular Pathogenesis and Implications in Clinical Practice. Neuroendocrinology 2021; 111:207-216. [PMID: 32403104 DOI: 10.1159/000508633] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 05/13/2020] [Indexed: 11/19/2022]
Abstract
Skeletal colonization is often regarded as a rare event in patients with neuroendocrine tumors (NETs) although both national registries and retrospective series report an incidence of bone metastases as high as 20% in subjects with advanced disease. While the biological mechanisms leading to bone metastatic colonization in NETs have been poorly investigated so far, key steps of osteotropic mechanisms, including the epithelial-to-mesenchymal transition, preparation of the premetastatic niche, migration of circulating tumor cells towards the bone marrow as well as the resulting alterations of the skeletal metabolism, are likely to operate also during the development of NET bone metastases. The skeleton involvement by NETs has a detrimental impact on both quality of life and patients' prognosis, leading to pain in the majority of symptomatic subjects. While it is currently unclear whether or not the earlier recognition of bone involvement by PET/CT imaging techniques employing 68Ga-DOTA-conjugated peptides might improve outcomes through the exploitation of timely treatments, the management of bone-colonizing NETs is today based only on clinical experience from other osteotropic tumors. Here, we summarize the fundamental molecular mechanisms driving bone colonization and revisit both established and novel treatments for patients with bone metastatic NETs.
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Affiliation(s)
- Mauro Cives
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy,
| | - Eleonora Pellè
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant' Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Daniela Prosperi
- Nuclear Medicine Unit, Sant' Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Marco Tucci
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Franco Silvestris
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, Sant' Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
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18
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Panzuto F, Rinzivillo M. Treatment of Intestinal NETs (Including Appendix). NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:201-210. [DOI: 10.1007/978-3-030-72830-4_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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19
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Sluiter NR, van der Bilt JD, Croll DMR, Vriens MR, de Hingh IHJT, Hemmer P, Aalbers AGJ, Bremers AJA, Ceelen W, D'Hoore A, Schoonmade LJ, Coupé V, Verheul H, Kazemier G, Tuynman JB. Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium. Clin Colorectal Cancer 2020; 19:e87-e99. [PMID: 32651131 DOI: 10.1016/j.clcc.2020.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/22/2019] [Accepted: 01/06/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. PATIENTS AND METHODS Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. RESULTS After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. CONCLUSION CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.
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Affiliation(s)
- Nina R Sluiter
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
| | | | - Dorothée M R Croll
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Menno R Vriens
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Patrick Hemmer
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Arend G J Aalbers
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Andreas J A Bremers
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Wim Ceelen
- Department of Surgery, University Hospital Ghent, Gent, Belgium
| | - Andre D'Hoore
- Department of Surgery, University Hospital Leuven, Leuven, Belgium
| | - Linda J Schoonmade
- Medical Library, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Veerle Coupé
- Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Henk Verheul
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Jurriaan B Tuynman
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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20
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Costa RDD, Kemp R, Santos JSD, Costa DAPD, Ardengh JC, Ribas-Filho JM, Ribas CAPM. THE ROLE OF CONVENTIONAL ECHOENDOSCOPY (EUS) IN THERAPEUTIC DECISIONS IN PATIENTS WITH NEUROENDOCRINE GASTROINTESTINAL TUMORS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2020; 33:e1512. [PMID: 32844878 PMCID: PMC7448866 DOI: 10.1590/0102-672020190001e1512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/23/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gastrointestinal neuroendocrine tumors are rare, usually presented as subepithelial or polypoid tumors. Accurate diagnosis and indication of the type of resection are still challenging. AIM To determine the effectiveness of echoendoscopy in determining the depth of the lesions (T) identified by endoscopy in order to evaluate surgical and/or endoscopic indication, and to evaluate the results of endoscopic removal in the medium term. METHODS Twenty-seven patients were included, all of whom underwent echoendoscopy for TN tumor staging and the evaluation of possible endoscopic resection. The parameters were: lesion size, origin layer, depth of involvement and identified perilesional adenopathies. The inclusion criteria for endoscopic resection were: 1) high surgical risk; 2) those with NET <2 cm; 3) absence of impairment of the muscle itself; and 4) absence of perilesional adenopathies in echoendoscopy and in others without distant metastases. Exclusion criteria were TNE> 2 cm; those with infiltration of the muscle itself; with perilesional adenopathies and distant metastases. The techniques used were: resection with polypectomy loop; mucosectomy with saline injection; and mucosectomy after ligation with an elastic band. The anatomopathological study of the specimens included evaluation of the margins and immunohistochemistry (chromogranin, synaptophysin and Ki 67) to characterize the tumor. Follow-up was done at 1, 6 and 12 months. RESULTS Resections with polypectomy loop were performed in 15 patients; mucosectomy in five; mucosectomy and ligation with elastic band in three and the remaining four were referred for surgery. The anatomopathological specimens and immunohistochemical analyzes showed positive chromogranin and synaptophysin, while Ki 67 was less than 5% among all cases. The medium-term follow-up revealed three recurrences. The average size of tumors in the stomach was 7.6 mm and in the duodenum 7.2 mm. Well-demarcated, hypoechoic, homogeneous lesions occurred in 75%; mucous layer in 80%; and the deep and submucosal mucosa in 70%. CONCLUSIONS Echoendoscopy proved to be a good method for the study of subepithelial lesions, being able to identify the layer affected by the neoplasm, degree of invasion, echogenicity, heterogeneity, size of the lesion and perilesional lymph node involvement and better indicate the treatment option.
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Affiliation(s)
- Rodrigo Dias da Costa
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
| | - Rafael Kemp
- Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - José Sebastião Dos Santos
- Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
| | | | - José Celso Ardengh
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
| | - Jurandir Marcondes Ribas-Filho
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
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Watson C, Tallentire CW, Ramage JK, Srirajaskanthan R, Leeuwenkamp OR, Fountain D. Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review. World J Gastroenterol 2020; 26:3686-3711. [PMID: 32742136 PMCID: PMC7366058 DOI: 10.3748/wjg.v26.i25.3686] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 06/04/2020] [Accepted: 06/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients’ perspective in conjunction with the disease presentation, severity and treatment.
AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.
METHODS The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection.
RESULTS Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’ HRQoL.
CONCLUSION HRQoL instruments offer a means to monitor patients’ general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.
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Affiliation(s)
- Catherine Watson
- PHMR Health Economics, Pricing and Reimbursement, London NW1 8XY, United Kingdom
| | | | - John K Ramage
- Kings Health Partners NET centre, Kings College Hospital London, London SE5 9RS, United Kingdom
| | | | | | - Donna Fountain
- PHMR Health Economics, Pricing and Reimbursement, London NW1 8XY, United Kingdom
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Abstract
Neuroendocrine neoplasms (NENs) of the gastrointestinal (GI) tract and pancreas are a rare and heterogeneous group of neoplasms characterized by common cellular features as well as unique site-specific traits. GI and pancreatic NENs are much rarer than the more common adenocarcinomas arising at these sites. However, the incidences of GI and pancreatic NENs have increased significantly, particularly in the stomach and common site, followed by rectum, appendix, colon, and stomach. Pancreatic NENs are also uncommon, with fewer than 1 per 100,000, accounting for 1% to 2% of all pancreatic neoplasms.
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23
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Li L, Huang S, Qiu L, Jiang W, Chen Z, Kang D, Tu H, Chen J, Zhou Y. Label-free identification of early gastrointestinal neuroendocrine tumors via biomedical multiphoton microscopy and automatic image analysis. IEEE ACCESS : PRACTICAL INNOVATIONS, OPEN SOLUTIONS 2020; 8:105681-105689. [PMID: 37197612 PMCID: PMC10187769 DOI: 10.1109/access.2020.3000289] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
At present, early diagnosis and treatment is the most effective way to treat early gastrointestinal neuroendocrine tumors. Therefore, we attempted to carry out multiphoton imaging of early neuroendocrine tumors because of its ability to label-free image tissue microstructure at the cellular level. Imaging results show that this imaging technique can quickly identify the histopathological changes in mucosa and submucosa caused by tumor invasion. Furthermore, we performed automatic image analysis on SHG images and extracted two optical diagnostic features-collagen density and average intensity, and also found obvious differences in the density as well as average intensity of collagen fibers in tumor microenvironment using a series of quantitative analysis. These findings may further facilitate the development of multiphoton microscopic imaging technique for clinical use.
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Affiliation(s)
- Lianhuang Li
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou 350007, P. R. China
| | - Shenghui Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
| | - Lida Qiu
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou 350007, P. R. China
- College of Physics and Electronic Information Engineering, Minjiang University, Fuzhou 350108, P. R. China
| | - Weizhong Jiang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
| | - Zhifen Chen
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
| | - Deyong Kang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
| | - Haohua Tu
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Jianxin Chen
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, Fujian Normal University, Fuzhou 350007, P. R. China
| | - Yongjian Zhou
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
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Gangi A, Manguso N, Gong J, Crystal JS, Paski SC, Hendifar AE, Tuli R. Midgut Neuroendocrine Tumors with Liver-only Metastases: Benefit of Primary Tumor Resection. Ann Surg Oncol 2020; 27:4525-4532. [PMID: 32394299 DOI: 10.1245/s10434-020-08510-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Management of metastatic midgut neuroendocrine tumors (MNET) remains controversial. The benefits of resecting the primary tumor are not clear and advocated only for select patients. This study aimed to determine whether resection of the primary MNET in patients with untreated liver-only metastases has an impact on survival. METHODS This retrospective study reviewed data of the National Cancer Database from 2004 to 2015 for patients with liver-only metastatic MNETs and compared those who received resection of their primary MNET with those who did not. Patient demographics, tumor characteristics, and clinical outcomes were compared between the groups. The primary outcome was overall survival (OS) after adjustment for patient, demographic, and tumor-related factors. RESULTS The study identified 1952 patients with a median age of 63 years (range, 18-90 years). The median primary tumor size was 2.4 cm (range, 0.1-20 cm). Of these patients, 1295 (66%) underwent resection of the primary tumor and 667 (34%) did not. The patients who underwent resection were younger (median age, 63 vs 65 years; p < 0.001) and had smaller primary tumors (median, 2.3 vs 3.0 cm; p < 0.001). The patients with clinical T1 or T2 tumors were significantly less likely to undergo resection than those with stage T3 or T4 tumors (58.5% vs 89.7%; p < 0.001). The median follow-up period was 43 months (range, 1-83 months). In the entire cohort, 483 deaths occurred, with a 5-year OS of 61%. The 5-year OS rate was 49% for the patients who underwent resection and 66% for those who did not (p < 0.001). When the patients were grouped according to T stage, no OS difference between resection and no resection for stages T1 (p = 0.07) and T2 (p = 0.40) was identified. However, the 5-year OS rate was significantly better for the resected patient cohort with T3 (67.5% vs 37.2%; p < 0.001) or T4 (59.8% vs 21.5%; p < 0.001) tumors. CONCLUSIONS The patients with treatment-naïve liver-only metastatic MNET had improved OS when the primary tumor was resected, particularly those with clinical stage T3 or T4 tumors. These patients may benefit from surgical resection of their primary tumor.
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Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Nicholas Manguso
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jun Gong
- Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Jessica S Crystal
- Division of Surgical Oncology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shirley C Paski
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Andrew E Hendifar
- Department of Gastrointestinal Malignancies, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Richard Tuli
- Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.,Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Fisher MD, Pulgar S, Kulke MH, Mirakhur B, Miller PJ, Walker MS, Schwartzberg LS. Treatment Outcomes in Patients with Metastatic Neuroendocrine Tumors: a Retrospective Analysis of a Community Oncology Database. J Gastrointest Cancer 2020; 50:816-823. [PMID: 30121904 PMCID: PMC6890585 DOI: 10.1007/s12029-018-0160-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Purpose Metastatic neuroendocrine tumors (mNETs) are rare, heterogeneous tumors that present diagnostic and treatment challenges, with limited data on the management of mNETs in clinical practice. The present study was designed to identify current diagnostic and treatment patterns in mNET patients treated in the US community oncology setting. Methods Patient-level data was collected from medical records of adults with mNETs from the Vector Oncology Data Warehouse, a comprehensive US community oncology network database. Results Of the 263 patients included (median follow-up, 22 months; range, 0.1–193.9), 30.4% (80/263) had intestinal tumors, 11.0% (29/263) had pancreatic, and 58.6% (154/263) had tumors of other or unknown location. Progression-free survival (PFS) from the start of first-line therapy differed significantly by tumor grade (log rank P = 0.0016) and location (P = 0.0044), as did overall survival (OS) (grade, P < 0.0001; location, P = 0.0068). Median PFS and OS for patients with undocumented tumor grade were shorter than for patients with G1/G2 tumors and longer than patients with G3 tumors. Median PFS and OS for patients with other or unknown tumors were shorter than for patients with intestinal tumors. Conclusions While potentially confounded by the high number of patients with other or unknown tumor locations, this retrospective study of patients in a US community oncology setting identified the importance of awareness of tumor grade and tumor location at diagnosis, as these were direct correlates of PFS and OS.
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Affiliation(s)
- Maxine D Fisher
- Vector Oncology, 6555 Quince Road, Suite 400, Memphis, TN, 38119, USA.
| | - Sonia Pulgar
- Ipsen Biopharmaceuticals, Inc., 106 Allen Road, Basking Ridge, NJ, 07920, USA
| | - Matthew H Kulke
- Boston Medical Center, Boston University School of Medicine, One Boston Medical Center Place, Boston, MA, 02118, USA
| | - Beloo Mirakhur
- Ipsen Biopharmaceuticals, Inc., 106 Allen Road, Basking Ridge, NJ, 07920, USA
| | - Paul J Miller
- Vector Oncology, 6555 Quince Road, Suite 400, Memphis, TN, 38119, USA
| | - Mark S Walker
- Vector Oncology, 6555 Quince Road, Suite 400, Memphis, TN, 38119, USA
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Abou Jokh Casas E, Pubul Núñez V, Anido-Herranz U, del Carmen Mallón Araujo M, del Carmen Pombo Pasín M, Garrido Pumar M, Cabezas Agrícola JM, Cameselle-Teijeiro JM, Hilal A, Ruibal Morell Á. Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. World J Gastroenterol 2020; 26:1513-1524. [PMID: 32308351 PMCID: PMC7152518 DOI: 10.3748/wjg.v26.i13.1513] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/06/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND 177Lu peptide receptor radionuclide therapy (PRRT) is a recently approved therapy in Spain that has been demonstrated to be a well-tolerated therapy for positive somatostatin receptor advanced gastroenteropancreatic neuroendocrine tumors.
AIM To determine the impact of PRRT on quality of life, radiologic and metabolic response, overall survival, prognostic factors and toxicity.
METHODS Thirty-six patients treated with 177Lu-PRRT from 2016 to 2019 were included. The most frequent location of the primary tumor was the gastrointestinal tract (52.8%), pancreas (27.8%), and nongastropancreatic neuroendocrine tumor (11.1%). The liver was the most common site of metastasis (91.7%), followed by distant nodes (50.0%), bone (27.8%), peritoneum (25.0%) and lung (11.1%). Toxicity was evaluated after the administration of each dose. Treatment efficacy was evaluated by two parameters: stable disease and disease progression in response evaluation criteria in solid tumors 1.1 criterion and prognostic factors were tested.
RESULTS From 36 patients, 55.6% were men, with a median age of 61.1 ± 11.8 years. Regarding previous treatments, 55.6% of patients underwent surgery of the primary tumor, 100% of patients were treated with long-acting somatostatin analogues, 66.7% of patients were treated with everolimus, 27.8% of patients were treated with tyrosine kinase inhibitor, and 27.8% of patients were treated with interferon. One patient received radioembolization, three patients received chemoembolization, six patients received chemotherapy. Hematological toxicity was registered in 14 patients (G1-G2: 55.5% and G3: 3.1%). Other events presented were intestinal suboclusion in 4 cases, cholestasis in 2 cases and carcinoid crisis in 1 case. The median follow-up time was 3 years. Currently, 24 patients completed treatment. Nineteen are alive with stable disease, two have disease progression, eight have died, and nine are still receiving treatment. The median overall survival was 12.5 mo (95% confidence interval range: 9.8–15.2), being inversely proportional to toxicity in previous treatments (P < 0.02), tumor grade (P < 0.01) and the presence of bone lesions (P = 0.009) and directly proportional with matching lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01), , primary tumor surgery (P = 0.03) and metastasis surgery (P = 0.045). In a multivariate Cox regression analysis, a high Ki67 index (P = 0.003), a mismatch in the lesion findings between Octreoscan and computed tomography pre-PRRT (P < 0.01) and a preceding toxicity in previous treatments (P < 0.05) were risk factors to overall survival.
CONCLUSION Overall survival was inversely proportional to previous toxicity, tumor grade and the presence of bone metastasis and directly proportional to matching lesion findings between Octreoscan and computed tomography pre-PRRT and primary tumor and metastasis surgery.
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Affiliation(s)
- Estephany Abou Jokh Casas
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - Virginia Pubul Núñez
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - Urbano Anido-Herranz
- Department of Oncology, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - María del Carmen Mallón Araujo
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - Maria del Carmen Pombo Pasín
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - Miguel Garrido Pumar
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
| | - José Manuel Cabezas Agrícola
- Department of Endocrinology, Santiago de Compostela´s University Hospital, Santiago de Compostela, 15706, A Coruña, Spain
| | | | - Ashraf Hilal
- Department of Statistics, University of Santiago de Compostela, Santiago de Compostela 15706, A Coruña, Spain
| | - Álvaro Ruibal Morell
- Department of Nuclear Medicine, Santiago de Compostela´s University Hospital, Santiago de Compostela 15706, A Coruña, Spain
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Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocr Rev 2020; 41:bnz004. [PMID: 31555796 PMCID: PMC7080342 DOI: 10.1210/endrev/bnz004] [Citation(s) in RCA: 123] [Impact Index Per Article: 24.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 02/28/2020] [Indexed: 02/07/2023]
Abstract
Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options.
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Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
| | - Gregory Kaltsas
- 1st Department of Propaupedic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Wouter W de Herder
- ENETS Center of Excellence, Section of Endocrinology, Department of Internal Medicine, Erasmus MC Cancer Center, Erasmus MC, Rotterdam, The Netherlands
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Asban A, Patel AJ, Reddy S, Wang T, Balentine CJ, Chen H. Cancer of the Endocrine System. ABELOFF'S CLINICAL ONCOLOGY 2020:1074-1107.e11. [DOI: 10.1016/b978-0-323-47674-4.00068-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Abstract
BACKGROUND Radiological and nuclear medical diagnostics play an important role in the work-up of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET). The sonographic examination, including contrast-enhanced examination, depicts an initial imaging modality to screen for NET. This report describes the sonomorphological behavior of ileal and pancreatic NET as well as hepatic metastases from NET. CLINICAL/METHODICAL ISSUE Sonographic evaluation of NET of the small intestine, pancreas and neuroendocrine hepatic metastases. STANDARD RADIOLOGICAL METHODS Contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), unenhanced ultrasonography. METHODICAL INNOVATIONS Contrast-enhanced ultrasound (CEUS). PERFORMANCE CEUS supports unenhanced ultrasound in the detection of NET and the differential diagnosis of unclear lesions, and is more sensitive for liver metastases (sensitivity according to the literature, 99% vs. 68%) PRACTICAL RECOMMENDATIONS: CEUS allows initial evaluation of NET and differentiation of benign vs. malignant lesions. Nevertheless, CEUS cannot replace more elaborate imaging modalities like CT or MRI for thorough staging examinations.
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30
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Leyden S, Kolarova T, Bouvier C, Caplin M, Conroy S, Davies P, Dureja S, Falconi M, Ferolla P, Fisher G, Goldstein G, Hicks RJ, Lawrence B, Majima Y, Metz DC, O'Toole D, Ruszniewski P, Wiedenmann B, Hollander R. Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals. Int J Cancer 2019; 146:1316-1323. [PMID: 31509608 PMCID: PMC7004101 DOI: 10.1002/ijc.32678] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 08/08/2019] [Accepted: 08/20/2019] [Indexed: 12/19/2022]
Abstract
Due to the increasing incidence and prevalence of neuroendocrine tumors (NETs), there is a need to assess any gaps in awareness and care. A survey was undertaken in 2017 to identify perceived unmet needs from the perspectives of patients/families, patient advocates and health care professionals (HCPs). The survey consisted of 33–37 questions (depending on type of respondent) across four areas: information, care, treatments and research. In total, 443 participants from 26 countries responded: 338 patients/families, 35 advocates and 70 HCPs. Perceived unmet needs regarding provision of information at diagnosis differed between groups. While 59% of HCPs believed they provided sufficient information, informational needs were mostly/fully met for only 30% of patients and 18% of advocates. Additionally, 91% of patients and 97% of advocates felt that patients had to search for information themselves. Availability of Gallium‐68‐Dotatate PET/CT scan was limited for the majority of patients (patients: 73%; advocates: 85%; HCP: 86%), as was access to treatments, particularly peptide receptor radionuclide therapy (patients: 42%; advocates: 95%; HCPs: 77%). All groups felt that standards of care, including psychological needs and diagnosis of mental health, were not fully met. Although about two‐thirds of patients were managed by a multidisciplinary team, 14% of patients reportedly did not have enough contact. All groups supported more patient involvement in research; patients and advocates prioritized improvement in diagnosis and HCPs focused on clinical trials. This survey revealed significant unmet needs but differing perceptions regarding these among the groups. There is a need for investigation and collaboration to improve standards of care for NET patients. What's new? Even though the incidence of neuroendocrine tumors (NETs) has been rising worldwide, the current management of patients varies considerably, potentially leaving many with suboptimal care. An international survey was carried out in 2017 to investigate unmet needs in the NET patient community. The survey revealed that patients perceive numerous unmet needs in key areas including provision of information, diagnostics and treatment access, care standards, and research involvement. While healthcare professionals were aware of these gaps, they generally underestimated their magnitude. Patients and healthcare professionals need to work together to improve the lives and prospects of the increasing numbers of patients.
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Affiliation(s)
| | | | | | - Martyn Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, United Kingdom
| | | | | | - Sugandha Dureja
- Department of Nuclear Medicine & Molecular Imaging, Fortis Memorial Research Institute, Gurgaon, Haryana, India
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Centre, San Raffaele Scientific Institute - "Vita e Salute" University, Milan, Italy
| | - Piero Ferolla
- Department of Internal Medicine and Endocrine Sciences, University of Perugia, Perugia, Italy
| | - George Fisher
- Stanford University School of Medicine, Stanford, CA
| | | | - Rodney J Hicks
- The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
| | - Ben Lawrence
- Discipline of Oncology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | | | - David C Metz
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Dermot O'Toole
- National Centre for Neuroendocrine Tumours, St. Vincent's University and Department of Clinical Medicine, St. James Hospital and Trinity College, Dublin, Ireland
| | | | - Bertram Wiedenmann
- Department of Hepatology, Gastroenterology and Endocrinology, Charité Medical School, Berlin, Germany
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Kıvrak Salim D, Bayram S, Gömceli İ, Çekin AH, Karaca M, Koçer M, Yıldız M. Palliative resection of primary site in advanced gastroenteropancreatic neuroendocrine tumors improves survivals. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:910-916. [PMID: 31625933 DOI: 10.5152/tjg.2019.19168] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND/AIMS Gastroenteropancreatic neuroendocrine tumors are rarely seen and have heterogeneous clinical outcomes. Mostly half of the patients had metastatic disease at presentation. Palliative resection of primary site in metastatic disease is still controversial. The aim of this study was to find out the influence of resection of primary tumor site on progression-free survival and overall survival in metastatic non-functioning gastroenteropancreatic neuroendocrine tumors. The secondary end point is to determine the prognostic factors influencing the survivals. MATERIALS AND METHODS This study was conducted at a single medical oncology center, Antalya Education and Research Hospital. Patients who had non-functioning metastatic gastroenteropancreatic neuroendocrine tumors with primary site resected or unresected were compared retrospectively. Resection of metastases was excluded. RESULTS Fifty-three patients were included in the study and 29 patients had primary tumor resection. The primary site resected group had favorable outcomes with the overall survival (median unreached) compared to the median overall survival of 30 months in the unresected group (p=0.001). Median progression-free survival was also better in the primary site resected group than the unresected group (60 months vs. 14 months, respectively) (p=0.013). In multivariate analysis, unresected primary site and high-grade tumors were found to be independent prognostic factors on low survivals (Hazard ratio (HR): 4.6; 95% CI: 1.21-17.47 and HR: 10.1; 95% CI: 1.15-88.84, respectively). Age (p=0.131), gender (p=0.051), chromogranin A level (p=0.104), Ki-67 index (p=0.550), tumor size (p=0.623), and primary tumor area (p=0.154) did not influence the overall survival. CONCLUSION Gastroenteropancreatic neuroendocrine tumors with primary site resected had improved survivals when compared to the unresected group.
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Affiliation(s)
- Derya Kıvrak Salim
- Department of Medical Oncology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - Selami Bayram
- Department of Medical Oncology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - İsmail Gömceli
- Department of Gastroenterological Surgery, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - Ayhan Hilmi Çekin
- Department of Gastroenterology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - Mustafa Karaca
- Department of Medical Oncology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - Murat Koçer
- Department of Medical Oncology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
| | - Mustafa Yıldız
- Department of Medical Oncology, University of Health Sciences, Antalya Training and Research Hospital, Antalya, Turkey
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32
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Weber F, Dralle H. Value of ileus-prophylactic surgery for metastatic neuroendocrine midgut tumours. Best Pract Res Clin Endocrinol Metab 2019; 33:101342. [PMID: 31628078 DOI: 10.1016/j.beem.2019.101342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Neuroendocrine tumours of the small intestine (SINET) are a rare disease. However, a rising incidence rate and excellent long-term survival, even in the setting of metastatic disease lead to a high prevalence of SINET of up to 11/100.000. At the time of diagnosis, most patients already suffer from metastatic disease. About one third of patients demonstrate localized or regional metastatic disease at time of presentation. For those patients the indication for curative surgery is not debated and 10-year cancer specific survival of almost 90% can be achieved. Due to major limitations of existing studies actually there is no sufficient evidence in favour of ileus-prophylactic palliative surgery for metastatic SINET. Until now the available evidence favouring an ileus-prophylactic palliative small bowel resection for stage IV SI-NET must be weighed against available high-level evidence from randomized trials that showed long-term survival under systemic therapy. Importantly, there is not a single study that indicates surgery for a symptomatic patient should be postponed. Because the majority of patients are symptomatic at the time of diagnosis, the rationale for an ileus-prophylactic palliative surgery is to operate before progression of mesenteric tumour mass and desmoplasia takes place and before intestinal obstruction and ischaemia occurs. To what extent a prophylactic palliative small bowel resection will provide a survival benefit in a situation where the mesenteric tumour mass cannot be resected radically is not clearly addressed by the current level of evidence.
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Affiliation(s)
- Frank Weber
- Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany.
| | - Henning Dralle
- Department of General, Visceral, and Transplantation Surgery, University Hospital Essen, Essen, Germany
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Shah CP, Mramba LK, Bishnoi R, Unnikrishnan A, Duff JM, Chandana SR. Survival trends of metastatic small intestinal neuroendocrine tumor: a population-based analysis of SEER database. J Gastrointest Oncol 2019; 10:869-877. [PMID: 31602324 DOI: 10.21037/jgo.2019.05.02] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background Incidence of small intestinal neuroendocrine tumors (SNETs) is increasing and they now comprise the most common types of small intestinal cancer. SNETs frequently present with distant metastasis. Significant uncertainty prevails with regards to the surgical management strategies in metastatic SNETs. Therefore, we aim to analyze survival trends in metastatic SNET patients stratified by type of surgical treatment. Methods We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2016 Sub (1973-2014 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with metastatic SNET between 2000 and 2014. Treatment received was divided into two broad categories; surgical resection and no surgery and further subcategorized into local resection (LR) (surgery of the primary tumor only) and radical resection (RR) (surgery for primary tumor and metastasectomy). Results We identified 1,138 metastatic SNET cases. Median age was 61 years. Median survival was 41 months and 5 year RSR was 72%. Age >50 years (HR 2.10, P<0.001), poorly differentiated histology (HR 3.50, P<0.001) and tumor size >2 cm (HR 1.27, P=0.07), showed poor outcome. The group which did not receive any tumor directed surgery showed the worst survival (5 years RSR 45.30% vs. 76%, respectively for no surgery vs. surgery group, P<0.001). We found no significant difference in survival between LR and RR (HR 1.01, 95% CI: 0.73-1.40, P=0.92). Upon further stratification, surgery significantly improved survival on patients who were >50 years (HR 0.37), and for primary tumor location in the duodenum (HR 0.13). Conclusions Surgery for the primary tumor (LR or RR) significantly improved 5-year survival even in the presence of distant metastasis irrespective of primary tumor size, grade, or histology. Poor prognostic factors include, age >50 years, duodenal primary, tumor size >2 cm, and poorly differentiated histology.
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Affiliation(s)
- Chintan P Shah
- Division Hematology & Oncology, University of Florida, Gainesville, FL, USA
| | - Lazarus K Mramba
- Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA
| | - Rohit Bishnoi
- Division Hematology & Oncology, University of Florida, Gainesville, FL, USA
| | | | - Jennifer M Duff
- Division Hematology & Oncology, University of Florida, Gainesville, FL, USA.,Department of Medicine, North Florida/South Georgia Veterans Health System, Gainesville, FL, USA
| | - Sreenivasa R Chandana
- Department of Medicine, Western Michigan University School of Medicine, Kalamazoo, MI, USA.,Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, USA.,Cancer and Hematology Centers of Western Michigan, Grand Rapids, MI, USA
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Altieri B, Di Dato C, Martini C, Sciammarella C, Di Sarno A, Colao A, Faggiano A. Bone Metastases in Neuroendocrine Neoplasms: From Pathogenesis to Clinical Management. Cancers (Basel) 2019; 11:cancers11091332. [PMID: 31500357 PMCID: PMC6770134 DOI: 10.3390/cancers11091332] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 08/28/2019] [Accepted: 09/05/2019] [Indexed: 12/20/2022] Open
Abstract
Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient’s quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.
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Affiliation(s)
- Barbara Altieri
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.
- Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Wuerzburg, 97080 Wuerzburg, Germany.
| | - Carla Di Dato
- Department of Clinical Medicine, Bufalini Hospital, 47521 Cesena, Italy.
| | - Chiara Martini
- Clinica Medica 3, Department of Medicine, DIMED, University of Padova, 35128 Padova, Italy.
| | - Concetta Sciammarella
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37126 Verona, Italy.
| | | | - Annamaria Colao
- Department of Clinical Medicine and Surgery, Federico II University, 80131 Naples, Italy.
| | - Antongiulio Faggiano
- Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
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Daskalakis K, Karakatsanis A, Hessman O, Stuart HC, Welin S, Tiensuu Janson E, Öberg K, Hellman P, Norlén O, Stålberg P. Association of a Prophylactic Surgical Approach to Stage IV Small Intestinal Neuroendocrine Tumors With Survival. JAMA Oncol 2019; 4:183-189. [PMID: 29049611 DOI: 10.1001/jamaoncol.2017.3326] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Importance Primary tumor resection and mesenteric lymph node dissection in asymptomatic patients with stage IV small intestinal neuroendocrine tumors (SI-NETs) are controversial. Objective To determine the association of locoregional surgery (LRS) performed at diagnosis with outcomes in patients with asymptomatic SI-NETs and distant metastases. Design, Setting, and Participants This cohort study included asymptomatic patients with stage IV SI-NETs diagnosed from January 1, 1985, through December 31, 2015, and identified using the prospective database of SI-NETs from Uppsala University Hospital, Uppsala, Sweden. Patients included were treated at a tertiary referral center and followed up until May 31, 2016, with data from the Swedish National Patient Register. The 363 patients with stage IV SI-NETs without abdominal symptoms were divided between those who underwent prophylactic up-front surgery within 6 months from diagnosis combined with oncologic treatment (hereafter referred to as LRS group [n = 161]) and those who underwent nonsurgical treatment or delayed surgery as needed combined with oncologic treatment (hereafer referred to as delayed LRS group [n = 202]). Exposures Prophylactic up-front surgery within 6 months from diagnosis combined with oncologic treatment vs nonsurgical treatment or delayed surgery as needed combined with oncologic treatment. Main Outcomes and Measures Overall survival (OS), length of hospital stay (LOS), postoperative morbidity and mortality, and reoperation rates measured from baseline. Propensity score matching was performed between the 2 groups. Results The 363 patients included 173 women (47.7%) and 190 men (52.3%), with a mean (SD) age at diagnosis of 62.4 (11.1) years. Two isonumerical groups with 91 patients in each resulted after propensity score matching. The LRS and delayed LRS groups were comparable in median OS (7.9 years [range, 5.1-10.7 years] vs 7.6 years [range, 5.8-9.5 years]; hazard ratio [HR], 0.98; 95% CI, 0.70-1.37; log-rank P = .93) and cancer-specific survival (7.7 years [range, 4.5-10.8 years] vs 7.6 years [range, 5.6-9.7 years]; HR, 0.99; 95% CI, 0.71-1.40; log-rank P = .99). No difference was found in 30-day mortality (0 patients in both matched groups) or postoperative morbidity (2 [2.2%] vs 1 [1.1%]; P > .99), median LOS (73 days [range, 2-270 days] vs 76 days [range, 0-339 days]; P = .64) or LOS due to local tumor-related symptoms (7.0 days [range, 0-90 days] vs 11.5 days [range, 0-69 days]; P = .81), or incisional hernia repairs (4 patients [4.4%] in both groups; P > .99). Patients in the LRS group underwent more reoperative procedures (13 [14.3%]) compared with those in the delayed LRS group (3 [3.3%]) owing to intestinal obstruction (P < .001). Conclusions and Relevance Prophylactic up-front LRS conferred no survival advantage in asymptomatic patients with stage IV SI-NETs. Delayed surgery as needed was comparable in all examined outcomes and was associated with fewer reoperations for intestinal obstruction. The value of a priori LRS in the presence of distant metastases is challenged and needs to be elucidated in a randomized clinical study.
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Affiliation(s)
- Kosmas Daskalakis
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Ola Hessman
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Heather C Stuart
- Division of Surgical Oncology, University of Miami, Miami, Florida
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Kjell Öberg
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Per Hellman
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Olov Norlén
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Peter Stålberg
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Cavalcoli F, Pusceddu S, Zilli A, Tamagno G, Femia D, Prinzi N, Travers J, Consonni D, Ciafardini C, Conte D, Massironi S. Effects of low-dose aspirin on clinical outcome and disease progression in patients with gastroenteropancreatic neuroendocrine neoplasm. Scand J Gastroenterol 2019; 54:1111-1117. [PMID: 31454281 DOI: 10.1080/00365521.2019.1656773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2019] [Revised: 08/11/2019] [Accepted: 08/12/2019] [Indexed: 02/08/2023]
Abstract
Objective: The chemopreventive effect of aspirin (ASA) has been observed in the setting of colorectal cancer and other solid neoplasms. Recently, ASA has demonstrated a promising anti-proliferative effect on GEP-NENs in vitro. However, the direct anti-neoplastic impact of ASA on GEP-NEN clinical outcome is yet to be clarified. Materials and methods: All the GEP-NEN patients followed up in three European Centers from January 2005 to September 2016 were retrospectively enrolled. Patients taking ASA in doses of 75-100 mg daily for cardiovascular prevention for at least six months were evaluated. The possible association between ASA and disease grading, staging, primary site, OS and PFS were evaluated. Results: Two hundred fifty one patients were included (117 males, median age 63 years). Of these, 64 patients were prescribed with ASA. No clear impact on OS or PFS was observed in GEP-NEN patients taking ASA compared to those not taking it. ASA intake was related with the patients' older age. At Cox multivariate analysis, stage IV and Ki-67 resulted independent predictors for OS and PFS. In the setting of intestinal NENs, a suggestive, but not statistically significant, protective role of ASA on PFS was observed [HR 0.41 (95% CI: 0.13-1.29)]. Conclusions: Despite ASA showed promising anti-proliferative effects in vitro and a chemopreventive action in NENs has been reported, a clear impact of ASA on survival in NENs has not emerged from the present study. However, in the subgroup of patients with small-intestine NENs, ASA showed a trend toward a protective role.
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Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Sara Pusceddu
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Gianluca Tamagno
- Department of Endocrinology/Diabetes, Mater Misericordiae University Hospital , Dublin , Ireland
| | - Daniela Femia
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - Natalie Prinzi
- Medical Oncology, Unit 1, ENETS Center of Excellence, Fondazione IRCCS Istituto Tumori Milano , Milan , Italy
| | - John Travers
- Department of Endocrinology/Diabetes, Mater Misericordiae University Hospital , Dublin , Ireland
| | - Dario Consonni
- Epidemiology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano , Milan , Italy
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Tsilimigras DI, Ntanasis-Stathopoulos I, Kostakis ID, Moris D, Schizas D, Cloyd JM, Pawlik TM. Is Resection of Primary Midgut Neuroendocrine Tumors in Patients with Unresectable Metastatic Liver Disease Justified? A Systematic Review and Meta-Analysis. J Gastrointest Surg 2019; 23:1044-1054. [PMID: 30671800 DOI: 10.1007/s11605-018-04094-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 12/28/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Patients with midgut neuroendocrine tumors (MNETs) frequently present with metastatic disease at the time of diagnosis. Although combined resection of the primary MNET and liver metastases (NELM) is usually recommended for appropriate surgical candidates, primary tumor resection (PTR) in the setting of extensive, inoperable metastatic disease remains controversial. METHODS A systematic review was performed according to PRISMA guidelines utilizing Medline (PubMed), Embase, and Cochrane library-Cochrane Central Register of Controlled Trials (CENTRAL) databases until September 30, 2018. RESULTS Among patients with MNET and NELM, 1226 (68.4%; range, 35.5-85.1% per study) underwent PTR, whereas 567 (31.6%; range, 14.9-64.5%) patients did not. Median follow-up ranged from 55 to 90 months. Cytoreductive liver surgery was performed in approximately 15.7% (range, 0-34.8%) of patients. Pooled 5-year overall survival (OS) among the resected group was approximately 73.1% (range, 57-81%) versus 36.6% (range, 21-46%) for the non-resection group. For patients without liver debulking surgery, PTR remained associated with a decreased risk of death at 5 years compared with patients who did not have the primary tumor resected (HR 0.36, 95% CI 0.16 to 0.79, p = 0.01; I2 58%, p = 0.12). For patients undergoing PTR, 30-day postoperative mortality ranged from 1.43 to 2%. CONCLUSION PTR was safe with a low peri-operative risk of mortality and was associated with an improved OS for patients with MNET and unresectable NELM. Given the poor quality of evidence, however, strong evidenced-based recommendations cannot be made based on these retrospective single center-derived data. Future well-design randomized controlled trials will be critical in elucidating the optimal treatment strategies for patients with MNET and advanced metastatic disease.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | | | - Ioannis D Kostakis
- Department of Transplantation, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Demetrios Moris
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Dimitrios Schizas
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
- Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, Oncology, Health Services Management and Policy, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite, Columbus, OH, 670, USA.
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The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic Count in Small Intestinal Neuroendocrine Tumors. Am J Surg Pathol 2019; 42:247-255. [PMID: 29016403 DOI: 10.1097/pas.0000000000000968] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Tumor cell proliferation rate determined by either Ki-67 index or mitotic count (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine tumors in general, and after its incorporation in the 2010 World Health Organization tumor grading system, it has become essentially mandatory in pathology reports for all gastrointestinal neuroendocrine tumors, regardless of tumor location. Nevertheless, clinical significance for the Ki-67 index or MC has not been well demonstrated in small intestinal neuroendocrine tumor (SINET), especially those without distant metastasis, the majority of which have very low proliferation rates. We assessed the clinical behavior of 130 SINETs in relation to stage, Ki-67 index, MC, and other pathologic features. Most SINETs (86%) were grade 1 and 14% were grade 2. There were no grade 3 tumors or poorly differentiated neuroendocrine carcinomas. On multivariate analysis, age, Ki-67 index >5%, MC >10/50 high-power field, stage IV, and liver metastases were associated with increased risk of death in all patients. When both stage and grade were considered, Ki-67 index >5% was associated with a nearly 4-fold increased risk of death in stage IV cases (n=60). In contrast, Ki-67 index did not show prognostic value for patients with stages I to III disease (n=70), although MC >1/50 high-power field was significantly associated with death on multivariable analysis. Our study confirms that liver metastasis and increased tumor cell proliferation rate are independent prognostic factors for SINETs, but shows that most SINETs have a very low proliferation rate, which limits its value for predicting tumor behavior. By combining staging and grading information, we demonstrate different roles and cutoff values of Ki-67 index and MC in SINET with different stages.
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Foubert F, Salimon M, Dumars C, Regenet N, Girot P, Venara A, Senellart H, Heymann MF, Matysiak-Budnik T, Touchefeu Y. Survival and prognostic factors analysis of 151 intestinal and pancreatic neuroendocrine tumors: a single center experience. J Gastrointest Oncol 2019; 10:103-111. [PMID: 30788165 DOI: 10.21037/jgo.2018.09.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Intestinal and pancreatic neuroendocrine tumors (IP-NETs) are rare tumors with heterogeneous outcomes. The aim of our study was to determine the clinical, therapeutic and pathological factors which impact the overall survival (OS) in IP-NETs. Methods All the patients diagnosed with IP-NETs at the Nantes University Hospital between October 1994 and October 2013 were retrospectively analysed. Patients with MEN-1 (Type 1 Multiple Endocrine Neoplasia) or Von Hippel-Lindau syndrome were excluded. Additionally, a prospective analysis of tumor grade (mitotic index and Ki67 index) was performed on tumor samples. OS was evaluated by Kaplan-Meier method and prognostic factors by log-rank test and Cox model. Results The study included 151 patients. Median age was 60 (range, 14-81). Primary tumor was pancreatic in 86 patients (56.95%) and intestinal in 65 patients (43.05%). Tumors were metastatic (synchronous or metachronous) in 72 patients (47.7%). The median OS was 157 months. For all IP-NETs, age >65 years (P<0.0001), Ki67 >5% (P=0.03), synchronous metastases (P=0.016), primary tumor size >25 mm (P=0.03) and emergency surgery (P=0.007) were independent poor prognostic factors. Conclusions In this large series of patients with IP-NET, age >65 years, Ki67 >5%, primary tumor size >25 mm, synchronous metastases and emergency surgery for acute complications have been identified as independent poor prognostic factors.
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Affiliation(s)
- Fanny Foubert
- IMAD, Department of Gastroenterology & Digestive Oncology, Nantes University Hospital, Nantes, France
| | - Maëva Salimon
- IMAD, Department of Gastroenterology & Digestive Oncology, Nantes University Hospital, Nantes, France
| | - Clotilde Dumars
- Department of Pathology, Nantes University Hospital, Nantes, France
| | - Nicolas Regenet
- IMAD, Department of Digestive Surgery, Nantes University Hospital, Nantes, France
| | - Paul Girot
- IMAD, Department of Gastroenterology & Digestive Oncology, Nantes University Hospital, Nantes, France
| | - Aurélien Venara
- Department of Digestive Surgery, Angers University Hospital, Angers, France.,INSERM U1235, Nantes University, Nantes, France
| | - Hélène Senellart
- Department of Medical Oncology, Cancer Research Institute, Saint Herblain, France
| | | | - Tamara Matysiak-Budnik
- IMAD, Department of Gastroenterology & Digestive Oncology, Nantes University Hospital, Nantes, France.,INSERM U1235, Nantes University, Nantes, France
| | - Yann Touchefeu
- IMAD, Department of Gastroenterology & Digestive Oncology, Nantes University Hospital, Nantes, France.,INSERM U1235, Nantes University, Nantes, France
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Rizzo FM, Vesely C, Childs A, Marafioti T, Khan MS, Mandair D, Cives M, Ensell L, Lowe H, Akarca AU, Luong T, Caplin M, Toumpanakis C, Krell D, Thirlwell C, Silvestris F, Hartley JA, Meyer T. Circulating tumour cells and their association with bone metastases in patients with neuroendocrine tumours. Br J Cancer 2019; 120:294-300. [PMID: 30636773 PMCID: PMC6353867 DOI: 10.1038/s41416-018-0367-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 11/26/2018] [Accepted: 12/04/2018] [Indexed: 02/03/2023] Open
Abstract
Background Bone metastases are associated with a worse outcome in patients with neuroendocrine tumours (NETs). Tumour overexpression of C-X-C chemokine receptor 4 (CXCR4) appears predictive of skeletal involvement. We investigated the role of circulating tumour cells (CTCs) and CXCR4 expression on CTCs as potential predictors of skeleton invasion. Methods Blood from patients with metastatic bronchial, midgut or pancreatic NET (pNET) was analysed by CellSearch. CXCR4 immunohistochemistry was performed on matched formalin-fixed paraffin-embedded (FFPE) samples. Results Two hundred and fifty-four patients were recruited with 121 midgut and 119 pNETs, of which 51 and 36% had detectable CTCs, respectively. Bone metastases were reported in 30% of midgut and 23% of pNET patients and were significantly associated with CTC presence (p = 0.003 and p < 0.0001). In a subgroup of 40 patients, 85% patients with CTCs had CTCs positive for CXCR4 expression. The proportion of CXCR4-positive CTCs in patients with bone metastases was 56% compared to 35% in those without (p = 0.18) it. Staining for CXCR4 on matched FFPE tissue showed a trend towards a correlation with CXCR4 expression on CTCs (p = 0.08). Conclusions CTC presence is associated with bone metastases in NETs. CXCR4 may be involved in CTC osteotropism and present a therapeutic target to reduce skeletal morbidity.
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Affiliation(s)
- Francesca M Rizzo
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Clare Vesely
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Alexa Childs
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Teresa Marafioti
- Department of Pathology, UCL Cancer Institute, University College London, London, UK
| | - Mohid S Khan
- Wales Neuroendocrine Tumour Service, Department of Gastroenterology, University Hospital of Wales, Cardiff, UK
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, Department of Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK
| | - Mauro Cives
- Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro", Bari, Italy
| | - Leah Ensell
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Helen Lowe
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Ayse U Akarca
- Department of Pathology, UCL Cancer Institute, University College London, London, UK
| | - TuVinh Luong
- Department of Histopathology, Royal Free London NHS Foundation Trust, London, UK
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Department of Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, Department of Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK
| | - Daniel Krell
- Neuroendocrine Tumour Unit, Department of Oncology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK
| | - Christina Thirlwell
- Department of Oncology, UCL Cancer Institute, University College London, London, UK.,Neuroendocrine Tumour Unit, Department of Oncology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK
| | - Franco Silvestris
- Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro", Bari, Italy
| | - John A Hartley
- Department of Oncology, UCL Cancer Institute, University College London, London, UK
| | - Tim Meyer
- Department of Oncology, UCL Cancer Institute, University College London, London, UK. .,Neuroendocrine Tumour Unit, Department of Oncology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK.
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Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms. J Gastrointest Surg 2019; 23:122-134. [PMID: 30334178 PMCID: PMC10183101 DOI: 10.1007/s11605-018-3986-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Accepted: 09/20/2018] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known. METHODS We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group. RESULTS Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months. CONCLUSIONS Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.
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Treatment challenges in and outside a network setting: Gastrointestinal neuroendocrine tumours. Eur J Surg Oncol 2019; 45:52-59. [DOI: 10.1016/j.ejso.2018.03.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 03/14/2018] [Indexed: 01/06/2023] Open
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The influence of embodied implicit power on fair decision making. ACTA PSYCHOLOGICA SINICA 2019. [DOI: 10.3724/sp.j.1041.2019.00106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Cives M, Strosberg JR. Gastroenteropancreatic Neuroendocrine Tumors. CA Cancer J Clin 2018; 68:471-487. [PMID: 30295930 DOI: 10.3322/caac.21493] [Citation(s) in RCA: 397] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/07/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor activity of everolimus has been demonstrated across a wide spectrum of NETs, and the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs). Chemotherapy with temozolomide and capecitabine has recently demonstrated an unprecedented prolongation of progression-free survival in a randomized trial of pNETs. Multiple retrospective series have reported the efficacy of liver-directed therapies both for palliating symptoms of hormone excess and for controlling tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been shown to reduce diarrhea in patients with carcinoid syndrome. Defining the therapeutic algorithm and identifying biomarkers predictive of response to treatments are among the main priorities for the next decade of research in the NET field.
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Affiliation(s)
- Mauro Cives
- Associate Professor, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy
| | - Jonathan R Strosberg
- Associate Professor, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
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177Lu-DOTATATE therapy in patients with neuroendocrine tumours including high-grade (WHO G3) neuroendocrine tumours: response to treatment and long-term survival update. Nucl Med Commun 2018; 39:789-796. [PMID: 29912750 DOI: 10.1097/mnm.0000000000000874] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE Upon diagnosis, distant metastases are encountered in 21-50% of neuroendocrine tumours (NETs). However, few systemic treatment options are available for the well-differentiated NETs in the metastatic stage. Lu-DOTATATE is one of the most effective treatments in this limited patient group. We retrospectively investigated its efficacy and effect on the survival in patients with both well-differentiated and grade III NETs who had high uptake in pretherapeutic Ga-DOTATATE PET/computed tomography scans. PATIENTS AND METHODS Patients with metastatic NETs treated with Lu-DOTATATE between January 2010 and November 2015 in our department were included in this retrospective cohort. Toxicity and adverse effects were evaluated according to SWOG criteria. Progression-free survival (PFS) and overall survival (OS) rates were calculated considering the first date of treatment. Response was evaluated according to RECIST criteria. Potential predictors of survival and response were analysed. RESULTS Patients (n=186) with metastatic NETs originating from various primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic-NETs, pheochromocytoma-paraganglioma and unknown primary) were treated with 1107 courses of Lu-DOTATATE treatment (median: 6; range: 3-12). Among 160 patients whose responses to treatment could be evaluated according to the RECIST criteria, 28.1% (n=45) had a progressive disease, 21.9% (n=35) had a stable disease, 46.9% (n=75) had a partial response and 3.1% (n=5) had a complete response. Median follow-up was 30.6 months. The Kaplan-Meier estimated median PFS was 36.4 months, mean PFS was 38 months and the mean OS was 55 months. The disease control rates in patients with WHO grades I, II and III were 74, 73 and 60%, respectively, and the OS rates were 61.9, 52.2 and 38.4 months, respectively. We observed no major renal toxicity except a minor increase (11.1%) in average serum creatinine levels. In 33.9% (n=56) of the patients, grade I toxicity; in 9.1% (n=15), grade II; and in 1.2% (n=2), grade III toxicity were observed. CONCLUSION Lu-DOTATATE therapy is an important treatment option in somatostatin receptor type-2-positive pancreatic, nonpancreatic gastroenteropancreatic-NETs, and lung NETs including metastatic NETs with an unknown primary site and significantly contributed to patients' OS. Additionally, peptide receptor radionuclide therapy may have a role in a selected subgroup of patients with grade III NET with high somatostatin receptor type-2 expression.
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Modlin IM, Kidd M, Malczewska A, Drozdov I, Bodei L, Matar S, Chung KM. The NETest: The Clinical Utility of Multigene Blood Analysis in the Diagnosis and Management of Neuroendocrine Tumors. Endocrinol Metab Clin North Am 2018; 47:485-504. [PMID: 30098712 PMCID: PMC6716518 DOI: 10.1016/j.ecl.2018.05.002] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The neuroendocrine neoplasms test (NETest) is a multianalyte liquid biopsy that measures neuroendocrine tumor gene expression in blood. This unique signature precisely defines the biological activity of an individual tumor in real time. The assay meets the 3 critical requirements of an optimal biomarker: diagnostic accuracy, prognostic value, and predictive therapeutic assessment. NETest performance metrics are sensitivity and specificity and in head-to-head comparison are 4-fold to 10-fold more accurate than chromogranin A. NETest accurately identifies completeness of surgery and response to somatostatin analogs. Clinical registry data demonstrate significant clinical utility in watch/wait programs.
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Affiliation(s)
- Irvin M Modlin
- Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520-8062, USA.
| | - Mark Kidd
- Wren Laboratories, 35 NE Industrial Road, Branford, CT 06405, USA
| | - Anna Malczewska
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, Katowice 40-514, Poland
| | - Ignat Drozdov
- Wren Laboratories, 35 NE Industrial Road, Branford, CT 06405, USA
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 77, New York, NY 10065, USA
| | - Somer Matar
- Wren Laboratories, 35 NE Industrial Road, Branford, CT 06405, USA
| | - Kyung-Min Chung
- Wren Laboratories, 35 NE Industrial Road, Branford, CT 06405, USA
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Eriksson J, Garmo JEH, Ihre-Lundgren C, Hellman P. Prognostic factors for death after surgery for small intestinal neuroendocrine tumours. BJS Open 2018; 2:345-352. [PMID: 30263986 PMCID: PMC6156160 DOI: 10.1002/bjs5.76] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 03/23/2018] [Indexed: 01/01/2023] Open
Abstract
Background Neuroendocrine tumours of the small intestine (SI-NETs) are rare gastrointestinal neoplasms with an annual incidence of about one per 100 000. Patients with apparently similar tumours have variable outcomes. The aim of this study was to identify postoperative prognostic factors identifiable after initial surgery. Methods This was a nested case-control study of patients with SI-NETs who were treated between 1961 and 2001. Data were retrieved from the Swedish Cancer Registry. Patients who died from the SI-NET and corresponding controls (who outlived cases by at least 1 month), matched by age at diagnosis and calendar period, were included. Sex, postoperative symptoms, postoperative 5-hydroxyindoleacetic acid (5-HIAA) values, European Neuroendocrine Tumor Society (ENETS) stage, insufficiency of the tricuspid valve, radical secondary surgery and secondary malignancy were studied as potential prognostic factors. Results In total, 1122 patients were included (561 cases, 561 controls). Postoperative factors of prognostic importance included hormone-related symptoms, stage IV disease, raised levels of 5-HIAA, insufficiency of the tricuspid valve, secondary surgery not being macroscopically radical and a second malignancy. Conclusion Stage and symptomatic disease are important prognostic factors in SI-NET.
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Affiliation(s)
- J Eriksson
- Department of Surgical Sciences Uppsala University Uppsala Sweden
| | - J E H Garmo
- Regional Oncological Centre Uppsala University Uppsala Sweden.,Cancer Epidemiology Unit, Division of Cancer Studies King's College London London UK
| | - C Ihre-Lundgren
- Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
| | - P Hellman
- Department of Surgical Sciences Uppsala University Uppsala Sweden
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Kayano D, Kinuya S. Current Consensus on I-131 MIBG Therapy. Nucl Med Mol Imaging 2018; 52:254-265. [PMID: 30100938 DOI: 10.1007/s13139-018-0523-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Revised: 03/27/2018] [Accepted: 04/12/2018] [Indexed: 12/24/2022] Open
Abstract
Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.
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Affiliation(s)
- Daiki Kayano
- 1Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.,2Department of Nuclear Medicine, Fukushima Medical University Hospital, 1 Hikariga-oka, Fukushima, 960-1295 Japan
| | - Seigo Kinuya
- 1Department of Nuclear Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
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Azam-Zangeneh H, Müller-Schilling M, Kandulski A. Neuroendokrine Neoplasien des Magens. DER GASTROENTEROLOGE 2018; 13:126-129. [DOI: 10.1007/s11377-018-0231-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Wu L, Fu J, Wan L, Pan J, Lai S, Zhong J, Chung DC, Wang L. Survival outcomes and surgical intervention of small intestinal neuroendocrine tumors: a population based retrospective study. Oncotarget 2018; 8:4935-4947. [PMID: 27903960 PMCID: PMC5354882 DOI: 10.18632/oncotarget.13632] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 11/08/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Small intestinal neuroendocrine tumors (SiNETs) without distant metastasis typically behave in an indolent manner, but there can be heterogeneity. We aimed to define the survival outcomes and impacts of surgical intervention. METHODS A retrospective cohort study was conducted by using data from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic features were analyzed in 4407 patients between 2000 and 2012. The cancer specific survival (CSS) was calculated by the Kaplan-Meier method. Multivariable Cox regression models with hazard ratios (HRs) were constructed to analyze survival outcomes and risk factors. RESULTS The adjusted incidence of early SiNETs is 1.3/100,000. Tumors are most commonly located in the ileum and are small (≤ 2 cm). The 5-year and 10-year CSS rates were 95.0% and 88.5%, respectively. Age > 50 years, large tumor size (> 2cm), poor differentiation, advanced T classification, and absence of surgical treatment were independent predictors of poor survival. Stratified analysis indicated that surgery significantly improved survival in patients that were white (HR, 0.45), > 50 years old (HR, 0.61), had duodenal tumors (HR, 0.43), large tumors (> 2cm) (HR, 0.32), advanced T classification (T3: HR, 0.29; T4: HR, 0.18) or well differentiation (HR, 0.55). There was no significant survival difference between local resection and radical resection (P =0.884). CONCLUSIONS Early SiNETs have a favorable prognosis. Surgical resection may improve outcomes, particularly in older patients and those with large tumors. More aggressive resections couldn't improve outcomes.
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Affiliation(s)
- Lunpo Wu
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jianfei Fu
- Department of Oncology, Zhejiang University Jinhua Hospital, Jinhua, Zhejiang Province, China
| | - Li Wan
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jie Pan
- Department of Endocrinology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Sanchuan Lai
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jing Zhong
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Daniel C Chung
- Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Liangjing Wang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.,Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
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