Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors.
OBJECTIVE
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.


CONCLUSIONS
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.
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Jonathan R
JR
Strosberg
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
George A
GA
Fisher
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Al B
AB
Benson
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Lowell B
LB
Anthony
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Bulent
B
Arslan
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
John F
JF
Gibbs
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Edward
E
Greeno
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Renuka V
RV
Iyer
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Michelle K
MK
Kim
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
William J
WJ
Maples
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Philip A
PA
Philip
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Edward M
EM
Wolin
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Dasha
D
Cherepanov
Jonathan R Strosberg, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.
Michael S
MS
Broder
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002454:Cell Differentiation; D032921:Consensus; D003697:Delphi Technique; D019317:Evidence-Based Medicine / Q000592:standards; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000556:secondary*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018579:Patient Selection; D016896:Treatment Outcome
D000970:Antineoplastic Agents
Consensus; Delphi technique; Expert testimony; Grade 1; Grade 2; Intermediate tumors; Low tumors; Neuroendocrine carcinomas; Neuroendocrine tumors; Pancreatic neoplasms; Treatment; Unresectable; Well-differentiated