Asymptomatic Small Pancreatic Endocrine Neoplasms.

Study Overview
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Brief Summary
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The aim of the study is to evaluate the most appropriate management of sporadic asymptomatic non-functioning pancreatic neuroendocrine neoplasms (NF-PNEN) ≤ 2 cm. P NF-PNEN management will be decided at the hospital and all therapeutics decision will be decided/coordinated by the treating physician. Patients will be either submitted to surgical resection or to active surveillance.

Detailed Description
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In the last decade a dramatic increase in diagnosis of small, incidentally discovered, NF-PNEN was observed. Various study indicates the safety of a conservative management for this lesion and the The European Neuroendocrine Tumor Society (ENETS) proposed a wait and see approach for small NF-PNEN. Indications for surgery include the presence of a localized NF-PNEN in the absence of distant metastases as curative resection of these tumors is associated with favourable prognosis especially for low grade. In the last decade a dramatic increase in diagnosis of small, incidentally discovered, NF-PNEN was observed.Moreover, other investigators observed a clear relationship between the tumor diameter and low risk of malignancy and systemic progression. In particular, a tumor size ≤ 2 cm seems to be associated with a negligible risk of disease recurrence and with a very low incidence of aggressive features such as lymph node involvement.On this basis, the European Neuroendocrine Tumor Society (ENETS) proposed a wait and see approach for small NF-PNEN when incidentally discovered. Since then, various series evaluated the safety of a conservative management for small, sporadic, incidentally diagnosed, NF-PNEN. After a median follow-up of 28-45 months, all the studies confirmed that an intensive surveillance for incidental and small NF-PNEN is safe in selected cases. Nevertheless, available data are based only on retrospective series with a significant heterogeneity of inclusion criteria and different tumor diameter cut-off and the appropriate management of this entities (surveillance versus surgery) is still a matter of debate.

Official Title
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A Prospective Evaluation of the Management of Sporadic Asymptomatic Nonfunctioning Pancreatic Neuroendocrine Neoplasms ≤ 2 cm

Conditions
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Non Functioning Pancreatic Endocrine Tumor

Intervention / Treatment
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* Diagnostic Test: Radiological imaging studies
* Other: Quality of Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Individuals with asymptomatic sporadic NF-PNEN ≤ 2 cm Diagnosis has to be proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging technique (CT or MR) that is positive at 68Gallium DOTATOC-PET scan or Octreoscan. Patients who undergo surgery for NF-PNEN<2cm within 12 months. In these cases, diagnosis has to be proven by histological confirmation of NF-PNEN Informed consent Exclusion Criteria: NF-PNEN > 2 cm of maximum diameter Presence of genetic syndrome (MEN1, VHL, NF) Presence of symptoms (specific symptoms suspicious of a clinical syndrome related to hypersecretion of bioactive compounds) or unspecific symptoms

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active surveillance group<br>Advised surveillance strategy consists of imaging studies (MR or EUS or US), every 6 months for the first two years and yearly thereafter for five years in the absence of significant changes on imaging or symptoms appearance. During surveillance, a high-quality imaging technique (MRI or CT) is mandatory at least every 12 months. Determination of CgA during follow-up is at physician's discretion. During follow-up, the treating physician is responsible for patient management and decision-making. | Diagnostic Test: Radiological imaging studies<br>* Patients will be submitted to radiological imaging studies (CT scan and/or MRI and/ or 68Gallium PET/CT and/or Octreoscan and/or EUS+FNAand/or Octreoscan and/or EUS+FNA) at diagnosis, and then every 6 months for the first two years and yearly thereafter for five years in the absence of significant changes on imaging or symptoms appearance. Every 12 months (or 6 months for patients with Ki67> 2%) a high quality imaging (CT scan or MRI) is required.<br>Other: Quality of Life Assessment<br>* quality of life and the perceived burden of surveillance or follow-up after surgery for participants, will be investigated by administrating HADS questionnaire and EORTC QLQ-C30 (version 3) and EORTC QLQ-GI.NET21 Module.<br>|
| Surgical resection group<br>Timing and type of resection will be established by the treating physician. Follow up strategy after surgery consists of imaging studies (MR or CT), every 6 months for the first two years and yearly thereafter for five years. An high-quality imaging technique (MRI or CT) is mandatory at least every 12 months. Determination of CgA during follow-up is at physician's discretion. During follow-up, the treating physician is responsible for patient management and decision-making. Date of surgery does not change the timing of follow up which starts from the date of enrolment. | Diagnostic Test: Radiological imaging studies<br>* Patients will be submitted to radiological imaging studies (CT scan and/or MRI and/ or 68Gallium PET/CT and/or Octreoscan and/or EUS+FNAand/or Octreoscan and/or EUS+FNA) at diagnosis, and then every 6 months for the first two years and yearly thereafter for five years in the absence of significant changes on imaging or symptoms appearance. Every 12 months (or 6 months for patients with Ki67> 2%) a high quality imaging (CT scan or MRI) is required.<br>Other: Quality of Life Assessment<br>* quality of life and the perceived burden of surveillance or follow-up after surgery for participants, will be investigated by administrating HADS questionnaire and EORTC QLQ-C30 (version 3) and EORTC QLQ-GI.NET21 Module.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease/progression-free survival of NF-PNEN ≤ 2 cm | The primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgical resection group) or death from disease. | From date of enrolment until the date of first documented progression or first evidence of recurrence, from 6 months up to 6 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of NF-PNEN ≤ 2 cm | The secondary end point is to evaluate the frequency of asymptomatic sporadic NF-PNEN ≤ 2 cm among overall sporadic NF-PNEN. Participating centers are required to give yearly the number of patients with NF-PNEN referred to their institution. | 6 years | 
| Outcome of surgical intervention of NF-PNEN ≤ 2 cm | Morbidity and mortality of patients submitted to surgical resection | from the date of surgery to 1 months later the surgery | 
| Epidemiology of patients submitted to surgical intervention for NF-PNEN ≤ 2 cm | Number of patients submitted to surgery andh type of surgical procedures. | from the date of surgery, up to 6 years | 
| Evolution of NF-PNEN ≤ 2 cm | NF-PNEN evolution, in terms of development of symptoms, tumour growth, development of distant metastases and secondary pancreatic duct dilatation. | From date of enrolment until the date of first documented radiological evolution, from 6 months up to 6 years. | 
| Quality of Life of NF-PNEN ≤ 2 cm | The perceived burden of surveillance or follow-up after surgery for participants, as assessed by questionnaires regarding attitude towards surveillance and general anxiety and depression (Hospital Anxiety and Depression scale, HADS). Quality of Life will be investigated, by filling in EORTC QLQ-C30 (version 3) and EORTC QLQ-GI.NET21 Module. | from 6 months up to 6 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NF-PNEN