Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2015; 21(8): 2450-2459
Published online Feb 28, 2015. doi: 10.3748/wjg.v21.i8.2450
Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors
Jonathan R Strosberg, George A Fisher, Al B Benson, Lowell B Anthony, Bulent Arslan, John F Gibbs, Edward Greeno, Renuka V Iyer, Michelle K Kim, William J Maples, Philip A Philip, Edward M Wolin, Dasha Cherepanov, Michael S Broder
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
George A Fisher, Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305, United States
Al B Benson, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, United States
Lowell B Anthony, Department of Internal Medicine, Division of Medical Oncology, University of Kentucky Markey Cancer Center, Lexington, KY 40536, United States
Bulent Arslan, Rush University Medical Center, Chicago, IL 60612, United States
John F Gibbs, Department of Surgery, University at Buffalo - State University of New York, Buffalo, NY 14260, United States
Edward Greeno, Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, United States
Renuka V Iyer, Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Michelle K Kim, Department of Medicine, Gastroenterology Mount Sinai School of Medicine, New York, NY 10029, United States
William J Maples, Mission Health System, Asheville, NC 28801, United States
Philip A Philip, Department of Oncology, Karmanos Cancer Institute, Detroit, MI 48201, United States
Edward M Wolin, Department of Internal Medicine, Division of Medical Oncology, University of Kentucky Markey Cancer Center, Lexington, KY 40536, United States
Dasha Cherepanov, Michael S Broder, Partnership for Health Analytic Research, LLC, Beverly Hills CA 90212, United States
Author contributions: Strosberg JR, Fisher GA, Benson AB, Cherepanov D and Broder MS designed the research, interpreted the findings, and drafted the manuscript; Strosberg JR, Fisher GA and the rest of members of the GEPNET Treatment Consensus Panel; Anthony LB, Arslan B, Gibbs JF, Greeno E, Iyer RV, Kim MK, Maples WJ, Philip PA, Wolin EM performed the research and contributed to interpretation of the findings and review of this research.
Supported by Grants from Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080, United States.
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: Michael S Broder, MD, MSHS, Partnership for Health Analytic Research, LLC, 280 South Beverly Drive, Suite 404, Beverly Hills, CA 90212, United States. mbroder@pharllc.com
Telephone: +1-310-8589555 Fax: +1-310-8589552
Received: March 26, 2014
Peer-review started: March 26, 2014
First decision: March 29, 2014
Revised: July 31, 2014
Accepted: October 21, 2014
Article in press: October 21, 2014
Published online: February 28, 2015
Processing time: 339 Days and 15.2 Hours
Abstract

AIM: To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs) and provide consensus treatment recommendations.

METHODS: Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs, angiogenesis inhibitors, inhibitors of mammalian target of rapamycin and cytotoxic agents. At this time, there is little data to guide treatment selection and sequence. We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations. Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process. After studying the literature, a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale. Ratings were done both before and after an extended discussion of the evidence. Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.

RESULTS: Specialties represented were medical and surgical oncology, interventional radiology, and gastroenterology. Panelists had practiced for a mean of 15.5 years (range: 6-33). Among 202 rated scenarios, disagreement decreased from 13.2% (26 scenarios) before the face-to-face discussion of evidence to 1% (2) after. In the final ratings, 46.5% (94 scenarios) were rated inappropriate, 21.8% (44) were uncertain, and 30.7% (62) were appropriate. Consensus statements from the scenarios included: (1) it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic; (2) it is appropriate to use everolimus, sunitinib, or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors; and (3) beyond first line, these same agents can be used. In patients with uncontrolled secretory symptoms, octreotide LAR doses can be titrated up to 60 mg every 4 wk or up to 40 mg every 3 or 4 wk.

CONCLUSION: Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.

Keywords: Unresectable; Neuroendocrine carcinomas; Neuroendocrine tumors; Well-differentiated; Grade 1; Grade 2; Low tumors; Intermediate tumors; Pancreatic neoplasms; Treatment; Consensus; Delphi technique; Expert testimony

Core tip: Using the RAND/UCLA modified Delphi process, physician experts obtained consensus on the appropriateness of various medical therapies in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors. Consensus statements were: (1) it is appropriate to use somatostatin analogs as first-line therapy in patients with hormonally-functional tumors and may be appropriate in asymptomatic patients; (2) it is appropriate to use everolimus, sunitinib, or cytotoxic chemotherapy as first-line therapy in patients with symptomatic or progressive tumors; and (3) beyond first-line, these same agents can be used. In patients with uncontrolled secretory symptoms, octreotide-LAR can be titrated up to 60 mg/4 wk or up to 40 mg/3 or 4 wk.