World Journal of GastroenterologyWorld J Gastroenterol 2017 September 7; 23(33): 6009-6196
ISSN 1007-9327 (print)ISSN 2219-2840 (online)
Published by Baishideng Publishing Group Inc
S
EDITORIAL
6009 Helminthsasanalternativetherapyforintestinaldiseases
Sipahi AM, Baptista DM
REVIEW
6016 Dextransodiumsulfatecolitismurinemodel:Anindispensabletoolforadvancingourunderstandingof
inflammatory bowel diseases pathogenesis
Eichele DD, Kharbanda KK
6030 Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments
Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D
MINIREVIEWS
6049 Colorectal cancer, screening and primary care: A mini literature review
Hadjipetrou A, Anyfantakis D, Galanakis CG, Kastanakis M, Kastanakis S
6059 Behavioral gastroenterology: An emerging system and new frontier of action
Jia L, Jiang SM, Liu J
ORIGINAL ARTICLE
Basic Study
6065 PharmacologicalevaluationofNSAID-inducedgastropathyasa"Translatable"modelofreferredvisceral
hypersensitivity
Hummel M, Knappenberger T, Reilly M, Whiteside GT
6077 HighyieldreproducibleratmodelrecapitulatinghumanBarrett’scarcinogenesis
Matsui D, Omstead AN, Kosovec JE, Komatsu Y, Lloyd EJ, Raphael H, Kelly RJ, Zaidi AH, Jobe BA
6088 Changes in expression of inhibitory substances in the intramural neurons of the stomach following
streptozotocin-induceddiabetesinthepig
Bulc M, Palus K, Zielonka L, Gajęcka M, Całka J
6100 HOXtranscriptantisenseintergenicRNArepressesE-cadherinexpressionbybindingtoEZH2ingastric
cancer
Chen WM, Chen WD, Jiang XM, Jia XF, Wang HM, Zhang QJ, Shu YQ, Zhao HB
Contents Weekly Volume 23 Number 33 September 7, 2017
� September 7, 2017|Volume 23|�ssue 33|WJG|www.wjgnet.com
ContentsWorld Journal of Gastroenterology
Volume 23 Number 33 September 7, 2017
6111 Ca2+/calmodulin-dependentproteinkinaseⅡregulatescoloncancerproliferationandmigrationvia
ERK1/2 and p38 pathways
Chen W, An P, Quan XJ, Zhang J, Zhou ZY, Zou LP, Luo HS
6119 AberrantDNA-PKcsandERGIC1expressionmaybeinvolvedininitiationofgastriccancer
Wang FR, Wei YC, Han ZJ, He WT, Guan XY, Chen H, Li YM
Retrospective Cohort Study
6128 Real world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis
Benson III AB, Broder MS, Cai B, Chang E, Neary MP, Papoyan E
Retrospective Study
6137 Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases
Halling ML, Kjeldsen J, Knudsen T, Nielsen J, Koch-Hansen L
6147 Suspiciousbrushcytologyisanindicationforlivertransplantationevaluationinprimarysclerosing
cholangitis
Boyd S, Vannas M, Jokelainen K, Isoniemi H, Mäkisalo H, Färkkilä MA, Arola J
6155 Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the
MALT1gene
Iwamuro M, Takenaka R, Nakagawa M, Moritou Y, Saito S, Hori S, Inaba T, Kawai Y, Toyokawa T, Tanaka T, Yoshino T,
Okada H
6164 Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy
Xie G, Zhou Q, Qiu CZ, Dai WK, Wang HP, Li YH, Liao JX, Lu XG, Lin SF, Ye JH, Ma ZY, Wang WJ
Observational Study
6172 Definition of colorectal anastomotic leakage: A consensus survey among Dutch and Chinese colorectal
surgeons
van Rooijen SJ, Jongen ACHM, Wu ZQ, Ji JF, Slooter GD, Roumen RMH, Bouvy ND
CASE REPORT
6181 How to treat intestinal obstruction due to malignant recurrence after Whipple’s resection for pancreatic head
cancer: Description of 2 new endoscopic techniques
Mouradides C, Taha A, Borbath I, Deprez PH, Moreels TG
6187 Arterioportal shunt incidental to treatment with oxaliplatin that mimics recurrent gastric cancer
Kim HB, Park SG
�� September 7, 2017|Volume 23|�ssue 33|WJG|www.wjgnet.com
ContentsWorld Journal of Gastroenterology
Volume 23 Number 33 September 7, 2017
LETTERS TO THE EDITOR
6194 Comment on “Effect of biofilm formation by clinical isolates of Helicobacterpylori on the efflux-mediated
resistancetocommonlyusedantibiotics”
Kazakos EI, Dorrell N, Polyzos SA, Deretzi G, Kountouras J
��� September 7, 2017|Volume 23|�ssue 33|WJG|www.wjgnet.com
�V September 7, 2017|Volume 23|�ssue 33|WJG|www.wjgnet.com
NAMEOFJOURNALWorld Journal of Gastroenterology
ISSNISSN 1007-9327 (print)ISSN 2219-2840 (online)
LAUNCHDATEOctober 1, 1995
FREQUENCYWeekly
EDITORS-IN-CHIEFDamian Garcia-Olmo, MD, PhD, Doctor, Profes-sor, Surgeon, Department of Surgery, Universidad Autonoma de Madrid; Department of General Sur-gery, Fundacion Jimenez Diaz University Hospital, Madrid 28040, Spain
Stephen C Strom, PhD, Professor, Department of Laboratory Medicine, Division of Pathology, Karo-linska Institutet, Stockholm 141-86, Sweden
Andrzej S Tarnawski, MD, PhD, DSc (Med), Professor of Medicine, Chief Gastroenterology, VA Long Beach Health Care System, University of Cali-fornia, Irvine, CA, 5901 E. Seventh Str., Long Beach,
CA 90822, United States
EDITORIALBOARDMEMBERSAll editorial board members resources online at http://www.wjgnet.com/1007-9327/editorialboard.htm
EDITORIALOFFICEJin-Lei Wang, DirectorYuan Qi, Vice DirectorZe-Mao Gong, Vice DirectorWorld Journal of GastroenterologyBaishideng Publishing Group Inc7901 Stoneridge Drive, Suite 501, Pleasanton, CA 94588, USATelephone: +1-925-2238242Fax: +1-925-2238243E-mail: [email protected] Desk: http://www.f6publishing.com/helpdeskhttp://www.wjgnet.com
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Contents
EDITORS FOR THIS ISSUE
Responsible Assistant Editor: Xiang Li Responsible Science Editor: Li-Juan WeiResponsible Electronic Editor: Yan Huang Proofing Editorial Office Director: Jin-Lei WangProofing Editor-in-Chief: Lian-Sheng Ma
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ONLINESUBMISSIONhttp://www.f6publishing.com
World Journal of GastroenterologyVolume 23 Number 33 September 7, 2017
Editorial Board Member of World Journal of Gastroenterology, Mostafa Sira, MD,AssociateProfessorofPediatricHepatology,GastroenterologyandNutri-tion, National Liver Institute, Menofiya University, Menofiya 32511, Egypt
World Journal of Gastroenterology (World J Gastroenterol, WJG, print ISSN 1007-9327, online ISSN 2219-2840, DOI: 10.3748) is a peer-reviewed open access journal. WJG was estab-lished on October 1, 1995. It is published weekly on the 7th, 14th, 21st, and 28th each month. The WJG Editorial Board consists of 1375 experts in gastroenterology and hepatology from 68 countries. The primary task of WJG is to rapidly publish high-quality original articles, reviews, and commentaries in the fields of gastroenterology, hepatology, gastrointestinal endos-copy, gastrointestinal surgery, hepatobiliary surgery, gastrointestinal oncology, gastroin-testinal radiation oncology, gastrointestinal imaging, gastrointestinal interventional ther-apy, gastrointestinal infectious diseases, gastrointestinal pharmacology, gastrointestinal pathophysiology, gastrointestinal pathology, evidence-based medicine in gastroenterol-ogy, pancreatology, gastrointestinal laboratory medicine, gastrointestinal molecular biol-ogy, gastrointestinal immunology, gastrointestinal microbiology, gastrointestinal genetics, gastrointestinal translational medicine, gastrointestinal diagnostics, and gastrointestinal therapeutics. WJG is dedicated to become an influential and prestigious journal in gas-troenterology and hepatology, to promote the development of above disciplines, and to improve the diagnostic and therapeutic skill and expertise of clinicians.
World Journal of Gastroenterology (WJG) is now indexed in Current Contents®/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch®), Journal Citation Reports®, Index Medicus, MEDLINE, PubMed, PubMed Central and Directory of Open Access Journals. The 2017 edition of Journal Citation Reports® cites the 2016 impact factor for WJG as 3.365 (5-year impact factor: 3.176), ranking WJG as 29th among 79 journals in gastroenterology and hepatol-ogy (quartile in category Q2).
I-IX EditorialBoard
ABOUT COVER
INDEXING/ABSTRACTING
AIMS AND SCOPE
FLYLEAF
Al B Benson III, Northwestern University, Chicago, IL 60208, United States
Michael S Broder, Eunice Chang, Elya Papoyan, Partnership for Health Analytic Research, LLC, Beverly Hills, CA 90212, United States
Beilei Cai, Maureen P Neary, Novartis Pharmaceuticals, East Hanover, NJ 07936, United States
Author contributions: All authors were equally involved in the design of the study; Chang E 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, No. NJ 07936-1080, United State.
Institutional review board statement: We conducted a retrospective cohort 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 meets 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.
Conflict-of-interest statement: Cai B and Neary MP are employees of Novartis Pharmaceuticals Corporation; Benson III AB was paid as a research consultant for the study as a subject matter expert by Novartis and is an employee of Northwestern University; Broder MS, Chang E and Papoyan E are employees of Partnership for Health Analytic Research, LLC (PHAR, LLC), a health services research company paid by Novartis to conduct this research.
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/
Manuscript source: Unsolicited manuscript
Correspondence to: Michael S Broder, MD, MSHS, Partnership for Health Analytic Research, LLC, 280 S. Beverly Drive, Suite 404, Beverly Hills, CA 90212,United States. [email protected] Telephone: +1-310-8589555Fax: +1-310-8589552
Received: February 9, 2017Peer-review started: February 9, 2017First decision: April 21, 2017Revised: May 9, 2017 Accepted: June 18, 2017 Article in press: June 19, 2017Published online: September 7, 2017
AbstractAIMTo describe real-world treatment patterns of gastro-intestinal neuroendocrine tumors (GI NET).
METHODSIn this retrospective cohort study, we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues (SSA), cytotoxic chemotherapy (CC), targeted therapy (TT), interferon
6128 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
ORIGINAL ARTICLE
Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis
Retrospective Cohort Study
Al B Benson III, Michael S Broder, Beilei Cai, Eunice Chang, Maureen P Neary, Elya Papoyan
Submit a Manuscript: http://www.f6publishing.com
DOI: 10.3748/wjg.v23.i33.6128
World J Gastroenterol 2017 September 7; 23(33): 6128-6136
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
(IF) and combinations. We identified patients at least 18 years of age, with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date, whichever was first.
RESULTSWe identified 2258 newly treated GI NET patients: mean (SD) age was 55.6 years (SD = 9.7), 47.2% of the patients were between 55 and 64 years, and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy (964 with octreotide LAR, 380 with octreotide SA, and 1 with lanreotide), 33.3% CC, 3.6% TT, and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line the-rapy duration was 361 d (449 d for SSA, 215 for CC, 267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common second-line was combination therapy with SSA. In graphical pattern analysis, there was no clear pattern visible after first line therapy.
CONCLUSIONIn this study, 60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.
Key words: Gastrointestinal neuroendocrine tumors; Treatment patterns; Insurance claims; Somatostatin analogue; Targeted therapy; Chemotherapy
© The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: In this retrospective study of real-world treatment patterns, somatostatin analogues were the most common initial pharmacologic treatment in patients with gastrointestinal neuroendocrine tumors, and most of the remaining patients began treatment with chemotherapy. However, despite the many treatment options, over half of the patients discontinued treatments after first line and only less than 10% of patients received any second-line pharmacotherapy. Given limitations of claims data to elucidate reasons for this lack of continued treatment, a study using more detailed clinical information such as medical charts or physician surveys is warranted.
Benson III AB, Broder MS, Cai B, Chang E, Neary MP, Papoyan E. Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis. World J Gastroenterol 2017; 23(33): 6128-6136 Available from: URL: http://www.wjgnet.com/1007-9327/full/v23/i33/6128.htm DOI: http://dx.doi.org/10.3748/wjg.v23.i33.6128
INTRODUCTIONNeuroendocrine tumors (NET) comprise a broad family of rare and often slow growing malignancies. NET can develop anywhere in the body and arise from neuroendocrine cells throughout the endocrine system[1,2]. Approximately two-thirds of NET tumors occur in the gastrointestinal (GI) tract. These sites include the stomach, small intestine, appendix, colon, and rectum[3]. NET secrete peptides and neuroamines that cause distinct syndromes (e.g., carcinoid syn-drome), in which case they are referred to as “functional” tumors. Clinical presentation depends on the site of the primary tumor and whether they are functional. Surgery may be curative in the early stages, but delayed diagnosis is typical.
While rare, the incidence and prevalence of NET appear to be increasing worldwide[4-8]. The incidence of NET in the United States increased from 10.9 cases per million person-years (PMPY) in 1973 to 52.5 PMPY in 2004, and to 69.8 PMPY in 2012 as reported using the United States Surveillance Epidemiology and End Results database[4,9]. Prevalence also increased and was reported as 216 per million per year for GI NET in the United States.
The management of GI NET is based on a variety of factors including stage, anatomic location, and the presence and type of symptoms. The most recent NCCN guidelines for unresectable and metastatic GI NET recommend somatostatin analogues (SSA) as first-line treatment, but do not recommend a particular treatment sequence for the remaining therapies[10]. Considering the heterogeneity of GI NET tumors and the resultant lack of specificity in guidelines, we aimed to describe the current real-world treatment patterns of GI NET in a large sample of patients.
MATERIALS AND METHODSData sourceWe conducted a longitudinal, retrospective cohort analysis of newly pharmacologically treated GI NET patients using two large United States commercial claims databases. Data from the Truven Health Analytics MarketScan database and the IMS Phar-Metrics database (both using dates from January 1, 2009 to December 31, 2014) were combined to increase sample size. To prevent duplicate records, patients with the same age, gender, region, and date of first GI NET diagnosis in a calendar year found in both databases were randomly removed from one of the databases. Both databases are Health Insurance Portability and Accountability Act compliant administrative claims databases that contain de-identified adjudicated medical claims (e.g., inpatient and outpatient services) and pharmacy claims (e.g., outpatient prescriptions) submitted for payment by
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Benson III AB et al . GI NET treatment patterns
providers, healthcare facilities, and pharmacies. For both data sources, claims include information on each physician visit, medical procedure, hospitalization, drug dispensed, date of service, number of days of medication supplied, test performed, and complete payment information. Each medical claim has a principal diagnosis and secondary diagnoses codes associated with it. Available patient demographic information includes age, gender, and geographic region. Dates of enrollment and disenrollment are also recorded. As the data were fully de-identified, this study was considered exempt from approval by the Institutional Review Board.
Cohort selectionPatients at least 18 years of age were identified from each dataset if they had at least 1 inpatient or 2 outpatient claims with an International Statistical Classification of Disease-9-Clinical Modification (ICD-9-CM) for GI NET (209.00-209.03, 209.10-209.17, 209.23, 209.24-209.27, 209.40-209.43, 209.50-209.57, 209.62, 209.65-209.67) during the study period (1/1/2009-12/31/2014). The first GI NET pharmacologic treatment claim on or after the appearance of the GI NET diagnosis code and within the ID period (7/1/2009 to 6/30/2014) was considered to be the index date. Patients were required to be enrolled for a baseline period of at least six months before the index date. To ensure new treatment, patients with any evidence of pharmacologic treatment during this baseline period were excluded. In order not to include the same patient twice, we searched for any patients with the same age, gender, region, and date of GI NET diagnosis who could be found in both databases, but we found none. Patient follow-up was variable and continued until the end of enrollment or the study end date (12/31/2014), whichever was first (Figure 1).
Study variables and measuresThe primary outcome measure was the use of pharmacologic or liver directed therapy. Pharmaco-therapy was divided into four groups: SSA, TT, CC and IF. SSA included octreotide and lanreotide, TT included everolimus and sunitinib, and CC included
temozolomide, streptozotocin, doxorubicin, liposomal doxorubicin, fluorouracil, capecitabine, dacarbazine, oxaliplatin and thalidomide. Pharmacologic therapy was identified in claims using both the Healthcare Common Procedure Coding System (HCPCS) and National Drug Codes (NDC). Liver directed therapies comprised liver resection, transplant, lesion ablation (using radiotherapy, cryotherapy, microwave and thermal energy, and including laparoscopic, open and percutaneous routes), embolization (including bland, radioisotope, and chemotherapy), and radiation therapy. Liver directed therapies were identified in claims using HCPCS, ICD-9-CM, and Current Procedural Terminology (CPT) codes. Chemotherapy observed only once and on the same date as embolization was considered chemoembolization and not part of a pharma-cologic regimen.
First-line therapy was defined as the pharmacologic treatment regimen observed on, or within three months of, the index date. Therapy included mono-therapy or combination therapies. A three-month period after the index date was used to identify pharmacologic therapy intended as first-line but not administered on the index date. This would include, for example, combination chemotherapy where the second agent is given after some delay. Second-line therapy was defined as beginning when treatment was switched from one category of pharmacotherapy to another (e.g., from SSA alone to CC alone), or when a new category of treatment was added (e.g., from SSA alone to SSA plus CC). Changes from one cytotoxic agent to another, or one SSA to another, were not considered a switch. The first day of treatment switch or addition was defined as the initiation date of second-line therapy.
Statistical analysisMeans and proportions were presented in tabular analyses. An inverse Kaplan-Meier curve was used to show duration of first-line therapy. All data transformations and statistical analyses were performed using SAS® version 9.4 (SAS Institute, Cary, NC). Graphical analyses were conducted using GRAPHx™, a proprietary graphics-based algorithm. The GRAPHx method uses multi-colored line segments to represent
6130 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
Figure 1 Study timeline. The first gastrointestinal neuroendocrine tumors (GI NET) pharmacologic treatment claim on or after the appearance of the GI NET diagnosis code and within the ID period (7/1/2009 to 6/30/2014) was considered to be the index date. Patients were required to be enrolled for a baseline period of at least six months before the index date. Patient follow-up was variable and continued until the end of enrollment or the study end date (12/31/14), whichever was first.
Day 1(first GI NET pharmacologic treatment)
6/30/14
Follow-up period(Until the end of enrollment or 12/31/14)
Identification period
7/1/09
1/1/09
6-mo washout period (No GI NET treatment)
12/31/14
Benson III AB et al . GI NET treatment patterns
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Mean duration of first-line therapy was 361 d (SD = 385) for all newly treated patients. The mean observed duration of treatment for first-line SSA monotherapy users was 449 d (SD = 434.2). It was 215 d (SD = 228.8) for first-line CC monotherapy and 267 d (SD = 325.7) for first-line TT monotherapy (Table 2). By 588 d of treatment (1.61 years), half of SSA initiators had discontinued treatment, compared to 182 d (0.498 years) for half of CC users and 171 d (0.47 years) for half of TT users to discontinue treatment (Figure 3). Liver directed therapy was used by 12.5% during first-line pharmacologic therapy; another 3.7% received it sometime after the first-line (Table 2).
By the end of the study follow-up period [mean (SD, median) of 576 d (447.1, 454)] 58.9% (n = 1331) patients had stopped pharmacologic therapy completely. These patients continued to be enrolled in one of the databases but no longer had claims for pharmacologic treatment. In Figure 4, these patients can be identified as colored line segments that terminate in gray segments of variable length, with the gray representing the period of no treatment. An additional 32.7% (n = 738) continued their initial therapy until the end of their enrollment; these patients were still receiving their first-line therapy at the time they left a covered plan or reached the end of study. This pattern is shown in Figure 4 as a colored segment terminating in white. The remaining 8.4% (n = 189) were observed to change pharmacologic treatment during the follow-up period (a colored segment terminating in different colored segment)
various treatments, plotting them over time. The images are reviewed visually for the presence and length of segments and change in colors and patterns over time.
RESULTSThere were 2900 and 2453 patients meeting the definition of GI NET who also had a claim for pharma-cologic treatment between 7/1/2009 and 6/30/2014 in the MarketScan and PharMetrics databases, respectively. After excluding patients who had treatment during a 6-mo pre-index period (and therefore were considered to be continuing, rather than initiating, treatment); received treatment before receiving a diagnosis of GI NET; were < 18 years old; or were not continuously enrolled in the 6-mo pre-index period, there remained 2258 newly treated GI NET patients who were included in the study (Figure 2).
Gender was evenly split with n = 1103 (48.8%) female patients and n = 1155 (51.2%) male. The average age was 55.6 years (SD = 9.7) and 47.2% of the patients were between 55 and 64 years. All regions of the United States were represented. More than half of patients, n = 1345 (59.6%), were treated with SSA as first-line monotherapy, 964 with octreotide LAR, 380 with octreotide SA, and 1 with lanreotide. An additional 75 patients (3.3%) received SSA in combination with other either CC, TT or IF. The second largest group, n = 752 (33.3%), was treated with CC monotherapy, and n = 81 (3.6%) received TT monotherapy (Table 1).
Figure 2 Patient identification. There were 2900 and 2453 gastrointestinal neuroendocrine tumors (GI NET) patients who also had a claim for pharmacologic treatment between 7/1/2009 and 6/30/2014 in the MarketScan and PharMetrics databases, respectively. After excluding patients who had treatment during a 6-mo pre-index period (and therefore were considered to be continuing, rather than initiating, treatment); received treatment before receiving a diagnosis of GI NET; were < 18 yr old; or were not continuously enrolled in the 6-mo pre-index period, there remained 2258 newly treated GI NET patients who were included in the study. 1Somatostatin analogues (SSAs), targeted therapy, cytotoxic chemotherapy, or interferon; 2324 (34.8%) within 3 mo, and 516 (55.4%) within 6 mo; 3249 (35.0%) within 3 mo, and 380 (53.4%) within 6 mo.
MarketScan database PharMetrics database
2900 GI NET patients received pharmacologic treatment1 in ID period
(7/1/2009-6/30/2014)
2453 GI NET patients received pharmacologic treatment1 in ID period
(7/1/2009-6/30/2014)
1 was < 18 yr old
430 had treatment in the 6mo pre-index period
9322 started treatment before the first GI NET diagnosis
7 were < 18 yr old
315 were not continuously enrolled in 6 mo pre-index period
264 were not continuously enrolled in 6 mo pre-index period
7113 started treatment before the first GI NET diagnosis
435 had treatment in the 6 mo pre-index period
2258 Newly treated GI NET patients
n = 2470
n = 1538
n = 1531
n = 1216 n = 1042
n = 1306
n = 1307
n = 2018
Benson III AB et al . GI NET treatment patterns
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(Fig
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t w
ith S
SA a
lone
or
in c
ombi
natio
n, m
ost
of t
he r
emai
nder
beg
an t
reat
men
t w
ith C
C, th
erap
y re
com
men
ded
Tabl
e 1 Pa
tien
t de
mog
raph
ics
by fi
rst-
line
trea
tmen
t n (
%)
Firs
t-lin
e tr
eatm
ent
All
new
ly t
reat
ed
patien
tsSS
AC
CTT
SSA
+ C
CSS
A +
TT
TT +
CC
IFSS
A +
IF
SSA
+ T
T +
CC
n13
451
752
81
42
31
3
2
1
1
2258
59.6
%33
.3%
3.6%
1.9%
1.4%
0.1%
0.1%
0.0
0.0
100.
0%A
ge (m
ean
± SD
, yr)
56.3
± 9
.554
.7 ±
9.9
54.9
± 1
0.5
53.5
± 1
0.9
53.8
± 1
0.1
59.3
± 3
.858
.5 ±
3.5
N/A
N/A
55.6
± 9
.7
18-2
46
(0.4
)2
(0.3
)0
(0)
1 (2
.4)
0 (0
)0
(0)
0 (0
)0
(0)
0 (0
)9
(0.4
)
25-3
420
(1.5
)25
(3.3
)4
(4.9
)3
(7.1
)0
(0)
0 (0
)0
(0)
0 (0
)0
(0)
52 (2
.3)
35
-44
121
(9.0
)92
(12.
2)9
(11.
1)4
(9.5
)4
(12.
9)0
(0)
0 (0
)0
(0)
0 (0
)23
0 (1
0.2)
45
-54
371
(27.
6)22
5 (2
9.9)
18 (2
2.2)
12 (2
8.6)
12 (3
8.7)
0 (0
)0
(0)
0 (0
)0
(0)
638
(28.
3)
55-6
465
1 (4
8.4)
338
(44.
9)39
(48.
1)20
(47.
6)11
(35.
5)3
(100
.0)
2 (1
00.0
)1
(100
.0)
1 (1
00.0
)10
66 (4
7.2)
65
+17
6 (1
3.1)
70 (9
.3)
11 (1
3.6)
2 (4
.8)
4 (1
2.9)
0 (0
)0
(0)
0 (0
)0
(0)
263
(11.
6)Fe
mal
e67
7 (5
0.3)
341
(45.
3)40
(49.
4)26
(61.
9)17
(54.
8)1
(33.
3)1
(50.
0)0
(0.0
)0
(0.0
)11
03 (4
8.8)
Regi
on
Mid
wes
t32
1 (2
3.9)
183
(24.
3)20
(24.
7)13
(31.
0)7
(22.
6)0
(0)
1 (5
0.0)
0 (0
)0
(0)
545
(24.
1)
Nor
thea
st26
1 (1
9.4)
150
(19.
9)12
(14.
8)11
(26.
2)7
(22.
6)1
(33.
3)0
(0)
0 (0
)0
(0)
442
(19.
6)
Sout
h56
3 (4
1.9)
323
(43.
0)36
(44.
4)12
(28.
6)15
(48.
4)2
(66.
7)1
(50.
0)0
(0)
1 (1
00.0
)95
3 (4
2.2)
W
est
200
(14.
9)96
(12.
8)13
(16.
0)6
(14.
3)2
(6.5
)0
(0)
0 (0
)1
(100
.0)
0 (0
)31
8 (1
4.1)
Year
of t
reat
men
t ini
tiatio
n13
0 (9
.7)
41 (5
.5)
4 (4
.9)
2 (4
.8)
1 (3
.2)
0 (0
)0
(0)
1 (1
00.0
)0
(0)
179
(7.9
)
2009
20
1027
1 (2
0.1)
122
(16.
2)4
(4.9
)11
(26.
2)7
(22.
6)0
(0)
1 (5
0.0)
0 (0
)0
(0)
416
(18.
4)
2011
282
(21.
0)15
9 (2
1.1)
15 (1
8.5)
17 (4
0.5)
5 (1
6.1)
0 (0
)0
(0)
0 (0
)0
(0)
478
(21.
2)
2012
270
(20.
1)16
8 (2
2.3)
33 (4
0.7)
4 (9
.5)
10 (3
2.3)
0 (0
)1
(50.
0)0
(0)
1 (1
00.0
)48
7 (2
1.6)
20
1326
8 (1
9.9)
174
(23.
1)16
(19.
8)3
(7.1
)4
(12.
9)2
(66.
7)0
(0)
0 (0
)0
(0)
467
(20.
7)
2014
124
(9.2
)88
(11.
7)9
(11.
1)5
(11.
9)4
(12.
9)1
(33.
3)0
(0)
0 (0
)0
(0)
231
(10.
2)D
ays
of fo
llow
-up
M
ean
621
514
454
588
425
244
675
836
496
576
(S
D)
(468
.5)
(409
.1)
(403
.6)
(424
.1)
(269
.6)
(140
.7)
(145
.7)
N/A
N/A
(447
.1)
M
edia
n50
039
329
045
536
021
667
583
649
645
4
1 964
with
oct
reot
ide
LAR,
380
with
oct
reot
ide
SA, a
nd 1
with
lanr
eotid
e. S
SA: S
omat
osta
tin a
nalo
gues
; CC
: Cyt
otox
ic c
hem
othe
rapy
; TT:
Tar
gete
d th
erap
y; IF
: Int
erfe
ron.
Benson III AB et al . GI NET treatment patterns
6133 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
1.0
0.8
0.6
0.5
0.4
0.2
0.0
Failu
re p
roba
bilit
y
0 0.47 0.498 1 1.61 2 3 4 5 Duration of first-line treatment, yr
Log-rank test: P < 0.001
CC
TTSSA
Point estimate (95%CI)SSA CC TT
75 percentile 3.35 (3.13-3.71) 0.75 (0.67-0.87) 1.70 (0.93-2.97)Median 1.61 (1.36-1.80) 0.498 (0.496-0.507) 0.47 (0.27-0.90)25 percentile 0.44 (0.36-0.52) 0.23 (0.19-0.27) 0.20 (0.16-0.24)
No. of patients at riskIndex date 0.5 yr 1 yr 1.5 yr 2 yr 2.5 yr 3 yr 3.5 yr 4 yr 4.5 yr 5 yr
SSA 1345 871 606 426 291 195 133 89 53 26 10CC 752 320 107 52 31 21 13 5 1 1 0TT 81 34 16 11 9 8 4 1 0 0 0
Figure 3 Time to discontinuation of first-line treatment. By 588 d of treatment (1.61 yr), half of SSA initiators had discontinued treatment, compared to 182 d (0.498 yr) for half of CC users and 171 d (0.47 yr) for half of TT users to discontinue treatment. SSA: Somatostatin analogues; CC: Cytotoxic chemotherapy; TT: Targeted therapy.
Day 1: First date of treatmentCopyright 2016. PHAR. LLC GRAPHx Version 1.0
500
1000
1500
2000
Day 1 Year 1 Year 2 Year 3 Year 4 Year 5
SSATTCCIFSSA + TTSSA + CCSSA + IFTT + CCSSA + TT + CCSSA + CC + IFLiver directed TxtNo treatmentNo data
Figure 4 Pharmacologic treatment. By end of study follow-up [mean (SD, median) of 576 d (447.1, 454)], 58.9% (n = 1331) patients had stopped pharmacologic therapy completely. These patients (no pharmacologic treatment claims, but remained enrolled in one of the databases) can be identified as colored line segments that terminate in gray segments of variable length, with the gray representing the period of no treatment. An additional 32.7% (n = 738) continued their initial therapy until the end of their enrollment; these patients were still receiving their first-line therapy at the time they left a covered plan or reached the end of study. This pattern is shown as a colored segment terminating in white. The remaining 8.4% (n = 189) were observed to change pharmacologic treatment during the follow-up period (a colored segment terminating in different colored segment). Liver directed therapy (short, red segments) appears dispersed throughout periods of both pharmacologic treatment (colored segments) and periods of no pharmacologic treatment (gray segments). SSA: Somatostatin analogues; CC: Cytotoxic chemotherapy; TT: Targeted therapy; IF: Interferon.
Benson III AB et al . GI NET treatment patterns
6134 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
by N
CCN
onl
y if
no o
ther
opt
ions
(SSA, TT
, or
liv
er d
irec
ted
trea
tmen
t) a
re fea
sibl
e. T
hird
, de
spite
the
man
y av
aila
ble
trea
tmen
t op
tions
, le
ss t
han
one
in 1
0 pa
tient
s w
as o
bser
ved
to rec
eive
tre
atm
ent w
ith s
econ
d-lin
e ph
arm
acot
hera
py o
f an
y ty
pe.
Each
of th
ese
findi
ngs
mus
t be
con
side
red
in lig
ht o
f w
hat
is k
now
n ab
out
the
dise
ase
as w
ell as
the
inh
eren
t lim
itatio
ns o
f th
e da
ta s
ourc
e. T
reat
ing
NET
pat
ient
s is
a c
ompl
ex p
roce
ss.
Trea
tmen
ts a
re ind
ivid
ualiz
ed b
ased
on
tum
or s
ize,
loc
atio
n, a
nd p
atho
logy
, as
wel
l as
whe
ther
the
tum
or is
func
tiona
l, ty
pe a
nd e
xten
t of
sy
mpt
oms,
and
spe
ed o
f pr
ogre
ssio
n. O
ur d
ata
did
not
incl
ude
this
lev
el o
f de
tail.
Ins
uran
ce c
ompa
nies
agg
rega
te inf
orm
atio
n on
inp
atie
nt a
nd o
utpa
tient
ser
vice
s (g
ener
ally
rep
orte
d as
ICD
-9-C
M o
r IC
D-1
0), pr
oced
ures
(IC
D-9
pro
cedu
re c
odes
and
CPT
cod
es)
and
phar
mac
y cl
aim
s (N
DC)
as c
laim
s ar
e su
bmitt
ed for
pay
men
t by
pr
ovid
ers,
hea
lthca
re fac
ilitie
s, a
nd p
harm
acie
s. S
o fo
r ex
ampl
e, w
hile
GI
NET
can
be
iden
tified
by
usin
g a
list
of I
CD
-9-C
M c
odes
, pr
esen
ce o
f ad
vanc
ed d
isea
se m
ust
be in
ferr
ed b
y ob
serv
ing
the
use
of p
harm
acol
ogic
tre
atm
ent. A
noth
er li
mita
tion
of t
he d
ate
sour
ce is
tha
t th
e av
aila
ble
leng
th o
f tim
e fo
r an
alys
is is
rel
ativ
ely
brie
f, so
co
nclu
sion
s re
gard
ing
aver
age
dura
tion
of u
se m
ay n
ot b
e re
pres
enta
tive
of lo
ng-t
erm
tre
atm
ent pa
tter
ns.
Our
prim
ary
findi
ng tha
t 60
% o
f pa
tient
s in
itiat
ed p
harm
acol
ogic
the
rapy
with
SSA is
con
sist
ent w
ith the
NCCN
rec
omm
enda
tion
of the
se d
rugs
for
initi
al tre
atm
ent
of c
linic
ally
sig
nific
ant
and
prog
ress
ive
NET
. Con
sist
ent
with
the
clin
ical
obs
erva
tion
that
SSA t
end
to b
e w
ell t
oler
ated
, pa
tient
s in
itiat
ing
trea
tmen
t w
ith S
SA r
emai
ned
on fi
rst-
line
ther
apy
long
er tha
n th
e pa
tient
s w
ho b
egan
tre
atm
ent w
ith C
C a
nd T
T. T
he s
econ
d fin
ding
not
ed a
bove
, th
at 1
/3 o
f G
I N
ET p
atie
nts
bega
n tr
eatm
ent w
ith
CC, is
mor
e su
rprisi
ng. CC is
rel
ativ
ely
inef
fect
ive
in the
se p
atie
nts,
and
as
a re
sult
is rec
omm
ende
d on
ly if
oth
er o
ptio
ns a
re n
ot fea
sibl
e.
Ther
e ar
e se
vera
l po
ssib
le e
xpla
natio
ns for
the
fre
quen
t us
e of
CC.
Patie
nts
obse
rved
to
initi
ate
cyto
toxi
c tr
eatm
ent
may
hav
e be
en t
reat
ed in
the
past
with
oth
er
agen
ts a
nd e
ither
pro
gres
sed
or w
ere
into
lera
nt t
o th
ose
agen
ts.
We
revi
ewed
dat
a fo
r 6
mo
befo
re t
he fi
rst
phar
mac
olog
ic t
reat
men
t, b
ut t
reat
men
ts m
ore
than
6
mo
in the
pas
t w
ould
hav
e be
en m
isse
d. I
t m
ay a
lso
be tha
t so
me
of the
pat
ient
s ha
d a
path
olog
y fin
ding
sug
gest
ing
chem
othe
rapy
wou
ld b
e be
nefic
ial,
or a
diff
eren
t ty
pe o
f G
I tu
mor
tha
t w
as in
corr
ectly
cod
ed a
s N
ET. O
ur d
ata
wer
e de
-ide
ntifi
ed, m
eani
ng w
e co
uld
not
confi
rm t
he d
iagn
osis
in m
edic
al r
ecor
ds, ph
ysic
ian
or p
atie
nt
surv
eys,
or
by o
ther
mea
ns.
Fina
lly,
som
e cl
inic
ians
may
hav
e be
en u
nfam
iliar
with
eith
er b
est
prac
tice
reco
mm
enda
tions
or
the
avai
labl
e, a
lbei
t lim
ited,
dat
a on
GI
NET
tre
atm
ent. O
ur fi
ndin
gs a
re c
onsi
sten
t w
ith a
rec
ent la
rge
case
ser
ies
from
a ter
tiary
ref
erra
l cen
ter
that
fou
nd S
SA a
nd C
C w
ere
the
two
mos
t co
mm
on tre
atm
ent
stra
tegi
es u
sed
for ga
stro
ente
ropa
ncre
atic
NET
[11].
Prev
ious
stu
dies
hav
e fo
und
sign
ifica
nt d
iver
genc
e be
twee
n cl
inic
al g
uide
lines
and
tre
atm
ent
in o
ther
, m
ore
com
mon
, ca
ncer
s. C
hagp
ar a
nd c
olle
ague
s fo
und
that
w
hile
Sta
ge I
col
on c
ance
r pa
tient
s w
ere
trea
ted
acco
rdin
g to
gui
delin
es b
y 95
%, hi
gher
sta
ge p
atie
nts
wer
e le
ss li
kely
to
be t
reat
ed a
ccor
ding
to
guid
elin
es. Sta
ge I
I
Tabl
e 2 U
se o
f fir
st-li
ne t
reat
men
t n (
%)
Firs
t-lin
eA
ll ne
wly
tre
ated
pa
tien
tsSS
AC
CTT
SSA
+ C
CSS
A +
TT
TT +
CC
IFSS
A +
IF
SSA
+ T
T +
CC
n13
4575
281
4231
32
11
2258
59.6
%33
.3%
3.6%
1.9%
1.4%
0.1%
0.1%
0.0%
0.0%
100.
0%D
urat
ion
of fi
rst-l
ine
trea
tmen
t (m
ean
± SD
, d)
449
± 43
4.2
215
± 22
8.8
267
± 32
5.7
408
± 32
7.9
276
± 18
9.5
208
± 16
5.6
251
± 28
5.0
836
± 0
426
± 0
361
± 38
5.0
Firs
t-lin
e en
ding
sta
tus
635
(47.
2)60
9 (8
1.0)
44 (5
4.3)
26 (6
1.9)
14 (4
5.2)
1 (3
3.3)
1 (5
0.0)
0 (0
)1
(100
.0)
1331
(58.
9)
Stop
Sw
itch
128
(9.5
)33
(4.4
)14
(17.
3)5
(11.
9)7
(22.
6)1
(33.
3)1
(50.
0)0
(0)
0 (0
)18
9 (8
.4)
End
of e
nrol
lmen
t58
2 (4
3.3)
110
(14.
6)23
(28.
4)11
(26.
2)10
(32.
3)1
(33.
3)0
(0)
1 (1
00.0
)0
(0)
738
(32.
7)Li
ver d
irec
ted
ther
apy
timin
gD
urin
g fir
st-li
ne17
1 (1
2.7)
87 (1
1.6)
9 (1
1.1)
10 (2
3.8)
4 (1
2.9)
1 (3
3.3)
0 (0
.0)
0 (0
.0)
0 (0
.0)
282
(12.
5)A
fter fi
rst-l
ine
36 (2
.7)
39 (5
.2)
7 (8
.6)
0 (0
.0)
2 (6
.5)
0 (0
.0)
0 (0
.0)
0 (0
.0)
0 (0
.0)
84 (3
.7)
+/- 3
0 d
afte
r sto
ppin
g fir
st li
ne
ther
apy1
635
609
4426
141
10
113
3129
(4.6
)42
(6.9
)2
(4.5
)0
(0.0
)0
(0.0
)0
(0.0
)0
(0.0
)0
(0.0
)0
(0.0
)73
(5.5
)
1 Am
ong
patie
nts
who
sto
pped
.
Benson III AB et al . GI NET treatment patterns
6135 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
high-risk patients showed the lowest concordance with only 36% being treated per recommendation[12]. In a prospective study of women with breast cancer, Giorano and colleagues found that 83% of patients 55-64 years old received care concordant with chemotherapy guidelines compared with 29% of patients 75 or older[13].
The finding that only a small proportion of patients are observed to receive second-line treatment is also surprising. The 5-year survival of patients with advanced GI NET is more than 70%. Most surviving patients would be expected to receive continued treatment, whether in the form of liver-directed treatment or pharmacotherapy. We considered multiple explanations for this finding. First, although median follow-up was over 15 mo, many patients were eventually lost to follow-up when they disenrolled from a plan included in our databases. One third of patients were continuing to use their index treatment when they were lost to follow-up. Whether (or when) these individuals progressed to second-line treatment cannot be determined using these databases. If these patients were systematically different from the ones who remained under observation, our results would be biased.
Despite this significant loss to follow-up, nearly 60% of patients were observed to continue enrollment but stop therapy. That is, they survived and remained in the data set, but no second-line pharmacotherapy use could be identified. We considered the possibility that these patients received some liver-directed treatment that alleviated their symptoms or controlled their disease, obviating the need for second-line treatment. However, we found no evidence of this: liver-directed treatment was observed in only 5.5% of patients around the time they stopped first-line treatment. We also considered whether some patients may have had a secondary source of payment, such that their claims for pharmacotherapy did not appear in our databases. Just over 11% of patients were 65
and older and would have been eligible for Medicare. Payment rules regarding patients with both commercial coverage and Medicare are complex[14] but generally require the commercial payer (for which we did have data) to be primarily responsible for payment. In cases where Medicare had primary responsibility, we would have missed claims for pharmacologic or liver-directed therapy and thus underestimated treatment. The magnitude of this problem is impossible to know using our current data source. A study using Medicare data and examining patients over 65 only might be less likely to suffer from this bias. Finally, it may indeed be the case that some patients stop therapy completely. Such patients may be terminal and choose not to undergo further treatment, or they may be relatively asymptomatic and decline to be treated on that basis. Further research with detailed clinical data would be needed to confirm which, if any, of these explanations is the most accurate.
In this large, claims-based, retrospective study of real-world pharmacologic treatment patterns, we found that 60% of GI NET patients began therapy with SSA and about one-third with CC. The relatively long time to discontinuation of SSA, as well as their use in combination with other agents, suggests they may be well tolerated and potentially have sustained effectiveness. We also found that over half of the patients discontinued treatment after first-line and only less than 10% of the patients received second-line treatment despite the availability of a number of different options. To address the limitations of this study and expand knowledge of real-world treat-ment patterns, a study using more detailed clinical information such as medical charts or physician surveys is warranted. In addition, future studies should consider using databases that would allow for greater longitudinal follow-up, such as registries, to assist in the further understanding of treatment patterns and length of therapy.
Table 3 Second-line treatment, stratified by first-line treatment n (%)
First-line treatment Patients with second-line treatmentSSA CC TT SSA + CC SSA + TT TT + CC IF
n 128 33 14 5 7 1 1 18967.7% 17.5% 7.4% 2.6% 3.7% 0.5% 0.5% 100.0%
Second-line treatment SSA + TT 51 (39.8) 4 (12.1) 4 (28.6) 3 (60.0) 0 (0) 1 (100.0) 63 (33.3) SSA + CC 33 (25.8) 6 (18.2) 0 (0) 5 (71.4) 0 (0) 0 (0) 44 (23.3) CC 24 (18.8) 4 (28.6) 0 (0) 1 (14.3) 0 (0) 0 (0) 29 (15.3) SSA 16 (48.5) 5 (35.7) 0 (0) 0 (0) 1 (100.0) 0 (0) 22 (11.6) TT 12 (9.4) 7 (21.2) 2 (40.0) 0 (0) 0 (0) 0 (0) 21 (11.1) SSA + IF 3 (2.3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 3 (1.6) IF 2 (1.6) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (1.1) TT + CC 1 (0.8) 0 (0) 1 (7.1) 0 (0) 0 (0) 0 (0) 2 (1.1) SSA + TT + CC 1 (0.8) 0 (0) 0 (0) 0 (0) 1 (14.3) 0 (0) 0 (0) 2 (1.1) SSA + CC + IF 1 (0.8) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (0.5)
SSA: Somatostatin analogues; CC: Cytotoxic chemotherapy; TT: Targeted therapy; IF: Interferon.
Benson III AB et al . GI NET treatment patterns
6136 September 7, 2017|Volume 23|Issue 33|WJG|www.wjgnet.com
COMMENTSBackgroundNeuroendocrine tumors (NET) comprise a broad set of rare tumors. Almost 2/3 arise in the gastrointestinal (GI) tract. The management of GI NET is based on a variety of factors including stage, anatomic location, and the presence and type of symptoms. The most recent NCCN guidelines for unresectable and metastatic GI NET recommend somatostatin analogues (SSA) as first-line treatment, but do not recommend a particular treatment sequence for the remaining therapies.
Research frontiersThis study’s results add to the limited knowledge about real-world treatment patterns for GI NET, which is especially significant in light of the lack of treatment guidelines regarding treatment sequences beyond first-line therapy.
Innovations and breakthroughsThis study used two very large, nationally representative claims databases to describe real-world treatment of GI NET. The three key findings were: first, the most common initial pharmacologic treatment was with SSA, with average duration of use of just over 18 mo; second, although 60% of patients initiated treatment with SSA alone or in combination, most of the remainder began treatment with cytotoxic chemotherapy, therapy recommended by NCCN only if no other options (SSA, targeted therapy, or liver directed treatment) are feasible; and third, despite the many available treatment options, less than one in 10 patients was observed to receive treatment with second-line pharmacotherapy of any type. The authors findings are consistent with a recent large case series from a tertiary referral center that found SSA and CC were the two most common treatment strategies used for gastroenteropancreatic NET. Previous studies have also found significant divergence between clinical guidelines and treatment in other, more common, cancers.
ApplicationsThis study suggests that there is frequent use of CC in GI NET treatment, although CC is relatively ineffective in these patients and recommended only if other options are not feasible. This may be a result of clinicians unfamiliarity with either best practice recommendations or the available, albeit limited, data on GI NET treatment. To address the limitations of this study and expand knowledge of real-world treatment patterns, a study using more detailed clinical information such as medical charts or physician surveys is warranted. In addition, future studies should consider using databases that would allow for greater longitudinal follow-up, such as registries, to assist in the further understanding of treatment patterns and length of therapy.
TerminologyNET arise from cells that release hormones in response to nerve stimulation. Insurance claims databases compile coded information related to charges for medical care for large populations, but they do not contain clinically detailed records.
Peer-reviewThe article aims to describe real-world treatment patterns of GI NET.
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P- Reviewer: Amornyotin S, Gazouli M S- Editor: Ma YJ L- Editor: A E- Editor: Zhang FF
Benson III AB et al . GI NET treatment patterns
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