Surgical Intervention and the NETest

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of different surgical resections (R0, R1, R2) on circulating NET transcripts (PCR score or NETest). A drop in circulating NET levels will be correlated with surgical excision. Secondly, variation of circulating NET transcripts will be correlated to NET recurrence to test whether this analysis may constitute an early predictive marker of disease relapse.

Detailed Description
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Biomarker-based tools that can accurately predict gastroenteropancreatic neuroendocrine tumor (GEP-NET) treatment response and tumor recurrence are currently not available. Circulating biomarkers that are associated with GEP-NETs are limited to measurements of plasma chromogranin A (CgA). The investigators have developed a PCR-based tool to quantitate (score) the circulating GEP-NET molecular signature (liquid biopsy) with high sensitivity and specificity. This signature can identify all types of GEP-NETs including small (1cm) non-metastatic tumors, is significantly reduced after tumor debulking and is decreased following surgical cure. Elevated post-surgical scores are associated with tumor recurrence within 6 months in  40% of cases. Current NET treatment protocols are associated with tumor recurrence (progression free survival) ranging from 5-18 months. The majority of patients will experience a relapse within 18 months irrespective of the treatment approach. The investigators hypothesize that a PCR measurement of circulating NET mRNA can accurately predict the extent of surgical resection (tumor removal) and elevated scores can predict tumor relapse before this occurs. This biomarker protocol seeks to test this hypothesis and evaluate whether changes in plasma CgA are as effective in predicting resection and recurrence.

Official Title
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Diagnosis of Neuroendocrine Neoplasms and Assessment of Response to Surgery by Means of Measurement of Gene Transcripts in Blood

Conditions
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Neuroendocrine Tumor, Gastroenteropancreatic

Intervention / Treatment
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* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed, well differentiated (G1, G2 or G3), local and advanced (metastatic), neuroendocrine tumor of gastro-enteropancreatic origin. Treatment-naïve as well as patients who have received previous therapies. Patients currently on LAR with clinically stable disease. CT or MRI documentation of disease. WHO performance status ≤2. Exclusion Criteria: Known history of HIV seropositivity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Post Surgery<br> | Procedure: Surgery<br>* Surgical excision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker prediction of tumor recurrence | Analysis of the alterations in the biomarker levels (from post-surgical levels, i.e., month 1) will be utilized to establish when the disease status has altered; a sustained increase in score will be recorded and compared with imaging to assess whether this is associated with disease progression/recurrence. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers and clinical symptomatology | Biomarker scores will be compared to the frequency of clinical symptoms, specifically flushing, to assess whether there is a relationship. | 24 months | 
| Biomarkers and clinical symptomatology | Biomarker scores will be compared to the frequency of clinical symptoms, specifically diarrhea, to assess whether there is a relationship. | 24 months |