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Asymptomatic Small Pancreatic Endocrine Neoplasms.

Recruiting
Conditions
Non Functioning Pancreatic Endocrine Tumor
Interventions
Diagnostic Test: Radiological imaging studies
Other: Quality of Life Assessment
Registration Number
NCT03084770
Lead Sponsor
IRCCS San Raffaele
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1000
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Active surveillance groupRadiological imaging studiesAdvised 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.
Surgical resection groupRadiological imaging studiesTiming 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.
Active surveillance groupQuality of Life AssessmentAdvised 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.
Surgical resection groupQuality of Life AssessmentTiming 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.
Primary Outcome Measures
NameTimeMethod
Disease/progression-free survival of NF-PNEN ≤ 2 cmFrom date of enrolment until the date of first documented progression or first evidence of recurrence, from 6 months up to 6 years.

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.

Secondary Outcome Measures
NameTimeMethod
Epidemiology of patients submitted to surgical intervention for NF-PNEN ≤ 2 cmfrom the date of surgery, up to 6 years

Number of patients submitted to surgery andh type of surgical procedures.

Evolution of NF-PNEN ≤ 2 cmFrom date of enrolment until the date of first documented radiological evolution, from 6 months up to 6 years.

NF-PNEN evolution, in terms of development of symptoms, tumour growth, development of distant metastases and secondary pancreatic duct dilatation.

Quality of Life of NF-PNEN ≤ 2 cmfrom 6 months up to 6 years.

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.

Frequency of NF-PNEN ≤ 2 cm6 years

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.

Outcome of surgical intervention of NF-PNEN ≤ 2 cmfrom the date of surgery to 1 months later the surgery

Morbidity and mortality of patients submitted to surgical resection

Trial Locations

Locations (1)

IRCCS San Raffaele Hospital

🇮🇹

Milan, Italy

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