ENETS Consensus Guidelines for the Management of Patients with Liver and Other Distant Metastases from Neuroendocrine Neoplasms of Foregut, Midgut, Hindgut, and Unknown Primary

Marianne Pavel; Eric Baudin; Anne Couvelard; Eric Krenning; Kjell Öberg; Thomas Steinmüller; Martin Anlauf; Bertram Wiedenmann; Ramon Salazar

doi:10.1159/000335597

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

Neuroendocrinology ◽

10.1159/000443167 ◽

2016 ◽

Vol 103 (2) ◽

pp. 172-185 ◽

Cited By ~ 391

Author(s):

M. Pavel ◽

D. O''Toole ◽

F. Costa ◽

J. Capdevila ◽

D. Gross ◽

...

Keyword(s):

Metastatic Disease ◽

Primary Site ◽

Unknown Primary ◽

Neuroendocrine Neoplasms ◽

Unknown Primary Site ◽

Consensus Guidelines ◽

Distant Metastatic Disease

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Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Neuroendocrinology ◽

10.1159/000504256 ◽

2019 ◽

Vol 110 (7-8) ◽

pp. 688-696

Author(s):

Kok Haw Jonathan Lim ◽

Hussain Raja ◽

Paolo D’Arienzo ◽

Jorge Barriuso ◽

Mairéad G. McNamara ◽

...

Keyword(s):

Bone Metastases ◽

Distant Metastases ◽

Unknown Primary ◽

Neuroendocrine Neoplasms ◽

Global Consensus ◽

Skeletal Related Events ◽

Grade 3 ◽

Review Current

Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. Methods: A retrospective study of all patients with NENs, except Grade 3 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12. Results: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n = 42) followed by lung (25%, n = 21), unknown primary (20%, n = 17), and “others” (6%, n = 5). Two-thirds (n = 57) had G1–2 neuroendocrine tumours, and 41% (n = 35) had functional tumours. Overall, 28% (n = 24) presented with synchronous BMs at first NEN diagnosis, and 55% (n = 47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n = 38), median time to development of BMs was 14.0 months. BMs were “widespread” in 61% (n = 52). Although only 22% (n = 19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n = 37). Radiotherapy and bisphosphonates were used in 34% (n = 29) and 22% (n = 19) respectively. Surgery was rarely performed (2%, n = 2). Median OS from identification of BMs was 31.0, and 18.9 months from development of BMs-related symptoms. Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients’ quality of life and survival outcomes.

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Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin

Minerva Endocrinologica ◽

10.23736/s0391-1977.19.03012-8 ◽

2020 ◽

Vol 44 (4) ◽

Cited By ~ 1

Author(s):

Krystallenia I. Alexandraki ◽

Marina Tsoli ◽

Georgios Kyriakopoulos ◽

Anna Angelousi ◽

Georgios Nikolopoulos ◽

...

Keyword(s):

Unknown Primary ◽

Neuroendocrine Neoplasms ◽

Diagnosis And Management ◽

Primary Origin ◽

Unknown Primary Origin

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Cancer of Unknown Primary: Challenges and Progress in Clinical Management

Cancers ◽

10.3390/cancers13030451 ◽

2021 ◽

Vol 13 (3) ◽

pp. 451

Author(s):

Noemi Laprovitera ◽

Mattia Riefolo ◽

Elisa Ambrosini ◽

Christiane Klec ◽

Martin Pichler ◽

...

Keyword(s):

Current Knowledge ◽

Distant Metastases ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

Diagnostic Strategies ◽

Molecular Features ◽

Tissue Of Origin ◽

Novel Therapeutic Strategies ◽

Aggressive Clinical Behavior

Distant metastases are the main cause of cancer-related deaths in patients with advanced tumors. A standard diagnostic workup usually contains the identification of the tissue-of-origin of metastatic tumors, although under certain circumstances, it remains elusive. This disease setting is defined as cancer of unknown primary (CUP). Accounting for approximately 3–5% of all cancer diagnoses, CUPs are characterized by an aggressive clinical behavior and represent a real therapeutic challenge. The lack of determination of a tissue of origin precludes CUP patients from specific evidence-based therapeutic options or access to clinical trial, which significantly impacts their life expectancy. In the era of precision medicine, it is essential to characterize CUP molecular features, including the expression profile of non-coding RNAs, to improve our understanding of CUP biology and identify novel therapeutic strategies. This review article sheds light on this enigmatic disease by summarizing the current knowledge on CUPs focusing on recent discoveries and emerging diagnostic strategies.

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Double-Balloon Enteroscopy in Detecting Small-Bowel Neuroendocrine Neoplasms: A Single-Center Prospective Study

Digestion ◽

10.1159/000511850 ◽

2020 ◽

pp. 1-9

Author(s):

Roberta Elisa Rossi ◽

Luca Elli ◽

Federica Branchi ◽

Dario Conte ◽

Sara Massironi

Keyword(s):

Small Bowel ◽

Neuroendocrine Neoplasm ◽

Unknown Primary ◽

Neuroendocrine Neoplasms ◽

Double Balloon Enteroscopy ◽

Balloon Enteroscopy ◽

Double Balloon ◽

Diagnostic Role ◽

Positive Results

Background and Aim: Small-bowel neuroendocrine neoplasm (sbNEN) diagnosis has improved with double-balloon enteroscopy (DBE). DBE efficacy in the detection of sbNENs is unknown. We aimed to report the experience at a single referral center for NENs. Methods: All consecutive patients with a suspected sbNEN selected for diagnostic DBE were enrolled. Results: Between 2011 and 2016, 25 patients were referred for a suspected sbNEN. In 15/25 patients, a primary NEN was detected outside the small bowel; in 4, NEN was excluded. After extensive workup, 6 patients (4 males, median age 50 years) underwent DBE (3 anterograde, 2 retrograde, and 1 both; median time: 60 min; median insertion 200 cm). DBE was positive in 3 patients: one had an ileal 2-cm NEN G1, one had an ileal 1.3-cm NEN G1, and one had an ileal 1-cm NEN G2, all surgically removed. Of the 3 other patients, one had a metastatic NEN of unknown primary, the other two had small intestinal NENs, both surgically removed (1.6-cm G1 and G2 NEN). DBE showed a sensitivity of 60% and, in absence of false-positive results, a specificity of 100%. Accuracy resulted 67%. No complications were observed. Conclusions: In line with data from the literature, the present series showed that DBE is a safe and effective procedure in the diagnosis of sbNENs. Further studies are needed to better clarify the diagnostic role of DBE in the neuroendocrine tumor setting and its relationship with other techniques.

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NEN: Advancement in Diagnosis and Minimally Invasive Therapy

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren ◽

10.1055/a-1030-4631 ◽

2019 ◽

Vol 192 (05) ◽

pp. 422-430

Author(s):

Daniel Putzer ◽

Peter Schullian ◽

Werner Jaschke ◽

Reto Bale

Keyword(s):

Metastatic Disease ◽

Symptom Control ◽

Distant Metastases ◽

Neuroendocrine Neoplasms ◽

Clinical Expertise ◽

Systemic Treatments ◽

Therapeutic Procedures ◽

Unresectable Liver Metastases ◽

Frequent Site ◽

Metastatic Involvement

Neuroendocrine neoplasms (NEN) are a heterogeneous type of malignant disease and frequently present with symptoms caused by the secretion of metabolically active substances or the manifestation of distant metastases, with the liver being the most frequent site of spreading. Early diagnosis of metastatic disease is recognized as the major prognostic factor in NEN patients. Complete surgical resection is feasible in only selected cases. For patients with unresectable liver metastases, various locoregional treatment approaches are available. Over the last decade, therapeutic procedures including locoregional and systemic treatments have been investigated for gastroenteropancreatic NEN (GEP-NEN), especially for metastatic disease to the liver. Only a few prospective clinical trials have compared these approaches, and the management of individual patients remains subject to clinical expertise and judgement. Locoregional treatments are applicable in patients with limited metastatic involvement of the liver, and may be used for tumor debulking and symptom control in patients with diffuse liver involvement. Key Points: Citation Format

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ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Functional Pancreatic Endocrine Tumor Syndromes

Neuroendocrinology ◽

10.1159/000335591 ◽

2012 ◽

Vol 95 (2) ◽

pp. 98-119 ◽

Cited By ~ 311

Author(s):

Robert T. Jensen ◽

Guillaume Cadiot ◽

Maria L. Brandi ◽

Wouter W. de Herder ◽

Gregory Kaltsas ◽

...

Keyword(s):

Endocrine Tumor ◽

Pancreatic Endocrine Tumor ◽

Neuroendocrine Neoplasms ◽

Consensus Guidelines

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Merkel cell carcinoma of unknown primary site

The Journal of Laryngology & Otology ◽

10.1017/s0022215107006378 ◽

2007 ◽

Vol 121 (4) ◽

Cited By ~ 11

Author(s):

Y Nazarian ◽

B Shalmon ◽

Z Horowitz ◽

L Bedrin ◽

M R Pfeffer ◽

...

Keyword(s):

Cell Carcinoma ◽

Head And Neck ◽

Merkel Cell Carcinoma ◽

Distant Metastases ◽

Primary Site ◽

Unknown Primary ◽

Merkel Cell ◽

Unknown Primary Site ◽

Carcinoma Of Unknown Primary ◽

Skin Malignancy

Merkel cell carcinoma is an uncommon and aggressive primary neuroendocrine skin malignancy which mostly affects the extremities and the head and neck region of elderly patients. Merkel cell carcinoma occurs with increased frequency in sun-exposed areas, in individuals exposed to arsenic and in immunosuppressed patients. Many patients with Merkel cell carcinoma present with other malignancies, mainly skin cancers. Characteristic features are frequent recurrences and regional and distant metastases. Mortality rates range from 20 to 65 per cent. The mainstay of treatment is surgery, with wide local excision, and adjuvant radiotherapy is usually administered. Merkel cell carcinoma of unknown primary site is rare, and the majority of the few cases described have not been from head and neck areas. We present a case of Merkel cell carcinoma of unknown primary site, with upper neck and distant metastases.

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Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis

Cancers ◽

10.3390/cancers12082246 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2246

Author(s):

Marina Tsoli ◽

Maria-Eleni Spei ◽

Göran Wallin ◽

Gregory Kaltsas ◽

Kosmas Daskalakis

Keyword(s):

Random Effects ◽

Primary Tumor ◽

Survival Benefit ◽

Tumor Resection ◽

Stage Iv ◽

Distant Metastases ◽

Primary Tumor Resection ◽

Cochrane Library ◽

Neuroendocrine Neoplasms ◽

Pancreatic Neuroendocrine Neoplasms

The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle–Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53–1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24–3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.

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