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Topic: Neuroendocrine Tumors

Circulating neuroendocrine tumors biomarkers. Why? When? How?
Suggestions for clinical practice from guidelines and consensus

Paola Razzore , Giorgio Arnaldi 2
1
1 SC Endocrinologia, AO Ordine Mauriziano, 10128 Turin, Italy.
2 Clinica di Endocrinologia e Malattie del Metabolismo, AOU Ospedali Riuniti, 60100 Ancona, Italy.
Corresponding Author: Dr. Paola Razzore, SC Endocrinologia, AO Ordine Mauriziano, Largo Turati 62, 10128 Torino, Italy.
E-mail: razzorepaola@hotmail.com

A B S T R AC T
Neuroendocrine neoplasms (NETs) are rare tumors that are increasing in incidence. NETs are characterized by heterogeneous
biological behaviour, clinical presentation and course. A sensitive and specific diagnostic and prognostic circulating biomarker
useful for all sites, grading and staging of neuroendocrine tumors is still an unmet need. The aim of this article was to review
current neuroendocrine and oncologic scientific society guidelines and position statements, and propose recommendations for
the most frequent clinical practice queries on circulating neuroendocrine tumors biomarkers. The authors searched for NCCN,
NANETS, ESMO, ENETS, UKINETS, AME management guidelines or position statements available from PubMed up to 7th
January 2016. From these results we chose guidelines or position statements published by scientific societies or institutions in
USA, Europe and Italy with recognized expertise in neuroendocrine tumor patient management. The authors present suggestions
for clinical practice based on this analysis.

Key words: Neuroendocrine tumors; neuroendocrine markers; neuroendocrine management; chromogranin A; guidelines;
clinical practice

INTRODUCTION values needs to be carefully considered with respect to
the clinical presentation and other putative diagnoses. [5,6]
Neuroendocrine tumors (NETs) are rare but have been Many different diagnostic and therapeutic approaches
increasing in incidence. NETs are characterized by are reported in real life NET manage-ment according to
[1]
heterogeneous biological behavior, clinical presentation, different physician expertise, accessibility of medical
and course. NETs arise from neuroendocrine cells care in different countries, and financial reimbursement.
aggregate in classical endocrine glands -- like adrenal, Translation of guidelines and consensus into clinical
pituitary and parathyroid -- but also in the diffuse practice is often difficult because suggestions are not
neuroendocrine system (DNES). always universally applicable.

An early diagnosis is crucial since lower survival was The aim of our paper was to review current neuroendocrine
demonstrated in patients with metastatic disease. and oncologic scientific society guidelines and position
[2]
However an interval of many years is reported from earliest statements and provide recommendations for the
symptoms to diagnosis. Symptoms are often nonspecific most frequent clinical practice queries on circulating
and do not lend themselves to identifying the specific neuroendocrine tumor biomarkers.
underlying tumor. In addition, clinical presentations
are protean and mimic a variety of other non-neoplastic We searched the National Comprehensive Cancer Network
diseases. Many specialists may be individually involved (NCCN), North American Neuroendocrine Tumor
[3]
from earliest signs and symptoms but a multidisciplinary (NANETS), European Society of Medical Oncology
team may be the most successsful approach to reduce (ESMO), European Neuroendocrine Tumor Society
time latency from symptoms to diagnosis and improve
overall survival. In this context the choice of circulating This is an open access article distributed under the terms of the Creative
[4]
neuroendocrine biomarkers and interpretation of these Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
the author is credited and the new creations are licensed under the identical
Access this article online terms.
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How to cite this article: Razzore P, Arnaldi G. Circulating
neuroendocrine tumors biomarkers. Why? When? How? Suggestions
for clinical practice from guidelines and consensus. J Cancer Metasta
DOI: Treat 2016;2:348-56.
10.20517/2394-4722.2016.39
Received: 08-02-2016; Accepted: 18-07-2016
348
©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc.