Blood transcript analysis and metastatic recurrent small bowel carcinoid management

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Abstract

Background

Detection of neuroendocrine tumor (NET) disease progression is a key issue in determining management. Currently, assessment is by imaging (MRI/CT and Octreoscan®) and plasma Chromogranin A (CgA) measurement.

Case presentation

We report use of a NET-specific multigene PCR-derived blood transcript signature (NET Index) to assess disease and correlated CgA and gene transcripts with MRI, CT, Octreoscan®, ¹¹C-5HTP-PET/CT and ⁶⁸Ga-DOTA-PET/CT in a patient with NET.

Conclusions

Our results identify limitations in evaluating disease status by CgA and identify that a PCR-based test is more sensitive. Alteration in NET blood gene transcript levels prior to image-based tumor confirmation suggests this parameter may also have utility as an index of therapeutic efficacy.

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Most cited references 27

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Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting.

James Ellis, Samuel E. Tepper, J Benedetti … (2011)

Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been increasing, and the estimated prevalence in the United States exceeds 100,000 individuals. The recent completion of several phase III studies, including those evaluating octreotide, sunitinib, and everolimus, has demonstrated that rigorous evaluation of novel agents in this disease is both feasible and can lead to practice-changing outcomes. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies for the US cooperative group program. Emphasis was placed on the development of well-designed clinical trials with clearly defined efficacy criteria. Key recommendations include the evaluation of pancreatic NET separately from NETs of other sites and the exclusion of patients with poorly differentiated histologies from trials focused on low-grade histologies. Studies evaluating novel agents for the control of hormonal syndromes should avoid somatostatin analog washout periods when possible and should include quality-of-life end points. Because of the observed long survival after progression of many patients, progression-free survival is recommended as a feasible and relevant primary end point for both phase III studies and phase II studies where a delay in progression is expected in the absence of radiologic responses.

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Neuroendocrine tumor disease: an evolving landscape.

Marianne Pavel, Göran Åkerström, Cláudio Almeida … (2012)

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.

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Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors.

Irvin Modlin, Daniel Chung, Anja T R Jensen … (2008)

A National Cancer Institute summit meeting on gastroenteropancreatic neuroendocrine and carcinoid tumors was held in September 2007 to present the currently accepted standards of care for patients with these tumors and to identify areas requiring investigation and development. These tumors are clinically and pathologically heterogeneous, present commonly with obscure symptoms that lead to delays in diagnosis of years, and have an incidence in the United States of 2.5 to 5 cases per 100,000. The 5-year survival rates range between 15% and 95%, depending on the site and extent of disease. This report delineates the main conclusions of the meeting, including the best practice diagnosis and treatment strategies for gastropancreatic neuroendocrine tumors, and the identification of clinical and scientific areas that are most in need of attention. The most pressing needs were public and physician education, identification of molecular markers for early diagnosis and therapeutic monitoring, improved imaging modalities and molecular prognostication, development of a standardized pathological classification system, and creation of regional centers of expertise with tumor and laboratory data banks. In addition, adequately validated neuroendocrine tumor models and cell lines should be established to investigate the molecular mechanisms involved in the control of their growth and secretion, and to facilitate the development of specific therapies that should be examined in well-designed multicenter studies of defined patient groups.

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Author and article information

Contributors

Irvin M Modlin: imodlin@optonline.net

Ignat Drozdov: idrozdov@beringresearch.com

Lisa Bodei: lisa.bodei@ieo.it

Mark Kidd: mark.kidd@yale.edu

Journal

Journal ID (nlm-ta): BMC Cancer

Journal ID (iso-abbrev): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date (Electronic): 5 August 2014

Publication date PMC-release: 5 August 2014

Publication date Collection: 2014

Volume: 14

Issue: 1

Electronic Location Identifier: 564

Affiliations

[ ]Wren Laboratories, 35 NE Industrial Road, Branford, CT 06405 USA

[ ]Bering Limited, Richmond, UK

[ ]Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy

[ ]Department of Surgery, Yale University School of Medicine, New Haven, CT 06510 USA

Article

Publisher ID: 4785

DOI: 10.1186/1471-2407-14-564

PMC ID: 4148943

PubMed ID: 25095873

SO-VID: bfe7604c-a47d-4f4b-a3fd-804b6a13b9b7

License:

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 17 September 2013

Date accepted : 22 July 2014

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: biomarker,blood,carcinoid,chromogranin a,68gallium,gene marker,neuroendocrine tumor,pcr,pet/ct

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: biomarker, blood, carcinoid, chromogranin a, 68gallium, gene marker, neuroendocrine tumor, pcr, pet/ct

Blood transcript analysis and metastatic recurrent small bowel carcinoid management

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Abstract

Background

Case presentation

Conclusions

Related collections

Karger: Oncology

Most cited references 27

Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting.

Neuroendocrine tumor disease: an evolving landscape.

Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors.

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Contributors

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Affiliations

Article

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