Project Summary

Neuroendocrine tumors (NETs) are a group of neoplasms that occur most frequently in the gastrointestinal tract, pancreas, and lungs, which are collectively referred to as gastroenteropancreatic (GEP-NETs) and lung-NETs. Because there are currently fewer than 180,000 patients living with this condition in the United States, NETs meet the criteria for rare disease status. NETs are typically slow growing, with vague signs and myriad symptoms, such as carcinoid syndrome, which leads to diagnostic delays. Consequentially, patients with NETs typically experience a prolonged clinical course with active disease, and many have significant symptom burdens. However, quality-of-life assessment outside of therapy trials remains scarce and of poor quality. Further, over half of patients with GEP-NETs are diagnosed with disease spread at diagnosis and are not candidates for curative surgery. Fortunately, many of these tumors are amenable to long-term medical treatment with somatostatin analogues (SSAs), which slow down the production of hormones—especially serotonin—which helps control the symptoms of carcinoid syndrome. However, living with distant spread of the disease increases the probability for the disease to progress. Following the failure of first-line SSA therapy, no clear consensus guidelines exist for the optimum sequencing of other therapeutic options. Patients with NETs are left facing the following questions: What therapy would be best to try next? If I were to take this option now, what treatment options will be closed off to me in the future? Clinicians are also unsure how best to tailor treatment selection to the characteristics of the patient and his or her tumor. Given that there are so many therapeutic options available (e.g., biologic therapy, liver directed therapy, radiotherapy, chemotherapy), the purpose of this project is to partner with patients on comparative effectiveness research (CER) to achieve the goal of alleviating undue toxicity and optimizing effectiveness and sequencing of therapy for patients with NETs. We will conduct a study of all newly occurring GEP-NET and lung-NET cases aged 18 years and older diagnosed between January 1, 2019, and December 31, 2023, across 14 participating PCORnet sites. In turn, we will enroll an average of 215 patients per site over the three-year study period (~3,000 patients total), allowing up to 60 months of follow-up for medical record outcomes.

Our study has four specific aims. Aim 1 will describe the frequency and sequencing of common treatment regimens in current use, and their association with various patient-reported outcomes (PROs), including quality of life and symptom burden, to answer the following patient question: What therapy would be best to try next? Aim 2 will determine whether patient (e.g., age, race, gender), clinical (e.g., preexisting conditions, medications and treatments), and tumor (e.g., stage, grade, nodal involvement) characteristics impact on the choice of therapies. Additionally, we will assess differences in survival and disease progression rates between common therapies, and combinations, to answer the following patient question: If I were to take this option now, what treatments will be closed off to me in the future? Aim 3, a specific CER study, will combine the PROs from aim 1 and medical record data from aim 2 to compare the effectiveness of peptide receptor radionuclide therapy regimens on outcomes of renal toxicity, disease progression, and quality of life. Finally, aim 4 will share the PCORnet infrastructure that this study generates to aid the conduct of future CER studies in this and other rare diseases.

There is currently no large nationally recruiting prospective (i.e., forward-in-time) observational study of patients with NETs. Our large study will robustly generate real-world evidence on the frequency and sequence of commonly used treatments for patients with GEP and lung-NETs in relation to PROs and survival/progression, endpoints that matter most to patients with NETs, their caregivers, and clinicians involved in their care. Given the lack of consensus guidelines as to the optimum sequencing of treatments, evidence generated in this study will aid patient, and clinician, navigation and selection of the next most appropriate therapy, accounting for the preferences and needs of the individual patient while respecting the underlying profile of his or her tumor. Moreover, the infrastructure this study will generate (i.e., electronic identification of patients with NETs, entry and completion of tumor table data in PCORnet, and a unique patient with NETs health record portal), will foster future CER studies in NETs and other rare diseases.

Project Information

Michael O'Rorke, PhD, BSc
University of Iowa

Key Dates

36 months
March 2021
July 2025


Project Status
Award Type
Research Priority Area


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Last updated: November 15, 2021