Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7283-7291
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7283
Predictive factors associated with carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors
Beilei Cai, Michael S Broder, Eunice Chang, Tingjian Yan, David C Metz
Beilei Cai, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, United States
Michael S Broder, Eunice Chang, Tingjian Yan, Partnership for Health Analytic Research, LLC, 280 S. Beverly Dr., Beverly Hills, CA 90212, United States
David C Metz, Division of Gastroenterology, University of Pennsylvania Health System, 3400 Civic Center Boulevard, Perelman Center for Advanced Medicine, Philadelphia, PA 19104, United States
Author contributions: All authors were equally involved in the design of the study; Chang conducted the statistical analyses; and all authors contributed equally in the interpretation of results and writing of the manuscript.
Supported by Novartis Pharmaceuticals, One Health Plaza, East Hanover, NJ 07936-1080, United States.
Institutional review board statement: We conducted a retrospective case-control study using the Truven Health Analytics MarketScan Database and the IMS Health PharMetrics Database, both commercial health insurance claims database for employer-insured beneficiaries in the United States. The databases are fully compliant with the Health Insurance Portability and Accountability Act and meet the criteria for a limited-use dataset. Since the patient and provider data included in this analysis were fully de-identified, this study was exempt from the Institutional Review Board review.
Informed consent statement: This study involved analyses of Health Insurance Portability and Accountability Act-compliant secondary databases, MarketScan and PharMetrics, thus no informed consent was feasible or necessary.
Conflict-of-interest statement: Cai is an employee of Novartis Pharmaceuticals Corporation. Broder, Chang, and Yan are employees of the Partnership for Health Analytic Research, LLC, which received funding from Novartis to conduct the researchdescribed in this manuscript. Metz is an employee of Northwestern University and was paid by Novartis to consult as a subject matter expert. Metz is Chair of the North American Neuroendocrine Tumor Society (NANETS) and also a consultant for Ipsen. Metz has received commercial research grants from Lexicon and Advanced Accelerator Applications (AAA), and is a consultant/on the advisory board for AAA.
Data sharing statement: The study statistician, Eunice Chang, conducted all statistical analysis for this study using Health Insurance Portability and Accountability Act-compliant commercial-insurance secondary databases MarketScan and PharMetrics.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Beilei Cai, PhD, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, United States. beilei.cai@novartis.com
Telephone: 1-862-309-8111 Fax: 973-781-7217
Received: June 29, 2017
Peer-review started: June 30, 2017
First decision: July 27, 2017
Revised: August 31, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: October 28, 2017
Processing time: 122 Days and 6.8 Hours
Abstract
AIM

To discover unknown factors associated with carcinoid syndrome (CS) with the goal of earlier diagnosis of CS.

METHODS

In this retrospective case-control study using United States administrative claims, patients (≥ 18 years) newly-diagnosed with gastrointestinal neuroendocrine tumors (GI NETs) without CS (controls) were exactly matched to patients with CS (cases) based on NET diagnosis date at a 3-to-1 ratio. Study index date was first CS diagnosis (controls: same distance from NET diagnosis as cases). The most observed conditions, excluding CS-associated symptoms/diagnoses, during the year before index date were assessed. Forward-stepwise logistic regression models were used to derive predictors, and were validated within another claims database.

RESULTS

In the development database, 1004 patients with GI NETs were identified; 251 (25%) had CS and 753 (75%) were controls. In the validation database, 724 patients with GI NETs were identified; 181 (25%) had CS and 543 (75%) were controls. A total of 33 common diagnoses (excluding conditions already known to be associated with CS) in the development database were entered in forward step-wise logistic regression models. In the final, validated logistic regression model, three factors prior to CS diagnosis were found consistently associated with higher risks for CS, including liver disorder [odds ratio (95%CI): 3.38 (2.07-5.51)], enlargement of lymph nodes [2.13 (1.10-4.11)], and abdominal mass [3.79 (1.87-7.69)].

CONCLUSION

GI NET patients with CS were 2-4 times as likely to have preexisting diagnoses (i.e., liver disorder, enlarged lymph nodes, abdominal mass) than non-CS patients.

Keywords: Carcinoid syndrome; Gastrointestinal neuroendocrine tumors; Predictive factors; Data mining

Core tip: By assessing patients with gastrointestinal neuroendocrine tumors from two independent United States claim databases, this study found that patients with carcinoid syndrome (CS) were 2-4 times as likely to have a preexisting diagnosis of a liver disorder, enlargement of lymph nodes, or abdominal mass than patients without CS.