Asymptomatic Small Pancreatic Endocrine Neoplasms.

NCT03084770 | Unknown

• 1 other identifier: ASPEN
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Functioning Pancreatic Endocrine Tumor

Keywords

NF-PNEN

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Frequency of NF-PNEN ≤ 2 cm

  6 years

• Outcome of surgical intervention of NF-PNEN ≤ 2 cm

  from the date of surgery to 1 months later the surgery

• Epidemiology of patients submitted to surgical intervention for NF-PNEN ≤ 2 cm

  from the date of surgery, up to 6 years

• Evolution of NF-PNEN ≤ 2 cm

  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

  from 6 months up to 6 years.

Study Arms (2)

Active surveillance group

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; Other: Quality of Life Assessment

Surgical resection group

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; Other: Quality of Life Assessment

Interventions

Radiological imaging studies DIAGNOSTIC_TEST

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.

Active surveillance group; Surgical resection group

Quality of Life Assessment OTHER

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.

Active surveillance group; Surgical resection group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with a newly diagnosis (less thn 12 months) of non- functioning pancreatic endocrine neoplasia (NF-PNEN) ≤ 2 cm of diameter. Either patients submitted to surgery or in active surveillance can be enrolled. Patients with sindrome or genetics disorders are excluded from the study.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele Hospital

Milan, 20132, Italy

RECRUITING

Related Publications (23)

• Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Kloppel G, Reed N, Kianmanesh R, Jensen RT; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. Neuroendocrinology. 2016;103(2):153-71. doi: 10.1159/000443171. Epub 2016 Jan 5. No abstract available.

  PMID: 26742109 BACKGROUND

• Jilesen AP, van Eijck CH, Busch OR, van Gulik TM, Gouma DJ, van Dijkum EJ. Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor. World J Surg. 2016 Mar;40(3):715-28. doi: 10.1007/s00268-015-3341-9.

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• Hashim YM, Trinkaus KM, Linehan DC, Strasberg SS, Fields RC, Cao D, Hawkins WG. Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surg. 2014 Feb;259(2):197-203. doi: 10.1097/SLA.0000000000000348.

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• Kuo EJ, Salem RR. Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in size. Ann Surg Oncol. 2013 Sep;20(9):2815-21. doi: 10.1245/s10434-013-3005-7. Epub 2013 Jun 15.

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• Vagefi PA, Razo O, Deshpande V, McGrath DJ, Lauwers GY, Thayer SP, Warshaw AL, Fernandez-Del Castillo C. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts General Hospital experience from 1977 to 2005. Arch Surg. 2007 Apr;142(4):347-54. doi: 10.1001/archsurg.142.4.347.

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• Crippa S, Partelli S, Zamboni G, Scarpa A, Tamburrino D, Bassi C, Pederzoli P, Falconi M. Incidental diagnosis as prognostic factor in different tumor stages of nonfunctioning pancreatic endocrine tumors. Surgery. 2014 Jan;155(1):145-53. doi: 10.1016/j.surg.2013.08.002.

  PMID: 24646958 BACKGROUND

• Birnbaum DJ, Gaujoux S, Cherif R, Dokmak S, Fuks D, Couvelard A, Vullierme MP, Ronot M, Ruszniewski P, Belghiti J, Sauvanet A. Sporadic nonfunctioning pancreatic neuroendocrine tumors: prognostic significance of incidental diagnosis. Surgery. 2014 Jan;155(1):13-21. doi: 10.1016/j.surg.2013.08.007. Epub 2013 Nov 12.

  PMID: 24238123 BACKGROUND

• Bettini R, Partelli S, Boninsegna L, Capelli P, Crippa S, Pederzoli P, Scarpa A, Falconi M. Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor. Surgery. 2011 Jul;150(1):75-82. doi: 10.1016/j.surg.2011.02.022.

  PMID: 21683859 BACKGROUND

• Haynes AB, Deshpande V, Ingkakul T, Vagefi PA, Szymonifka J, Thayer SP, Ferrone CR, Wargo JA, Warshaw AL, Fernandez-del Castillo C. Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes. Arch Surg. 2011 May;146(5):534-8. doi: 10.1001/archsurg.2011.102.

  PMID: 21576607 BACKGROUND

• Cherenfant J, Stocker SJ, Gage MK, Du H, Thurow TA, Odeleye M, Schimpke SW, Kaul KL, Hall CR, Lamzabi I, Gattuso P, Winchester DJ, Marsh RW, Roggin KK, Bentrem DJ, Baker MS, Prinz RA, Talamonti MS. Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors. Surgery. 2013 Oct;154(4):785-91; discussion 791-3. doi: 10.1016/j.surg.2013.07.004.

  PMID: 24074416 BACKGROUND

• Partelli S, Gaujoux S, Boninsegna L, Cherif R, Crippa S, Couvelard A, Scarpa A, Ruszniewski P, Sauvanet A, Falconi M. Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). JAMA Surg. 2013 Oct;148(10):932-9. doi: 10.1001/jamasurg.2013.3376.

  PMID: 23986355 BACKGROUND

• Falconi M, Bartsch DK, Eriksson B, Kloppel G, Lopes JM, O'Connor JM, Salazar R, Taal BG, Vullierme MP, O'Toole D; Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95(2):120-34. doi: 10.1159/000335587. Epub 2012 Feb 15. No abstract available.

  PMID: 22261872 BACKGROUND

• Gaujoux S, Partelli S, Maire F, D'Onofrio M, Larroque B, Tamburrino D, Sauvanet A, Falconi M, Ruszniewski P. Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2013 Dec;98(12):4784-9. doi: 10.1210/jc.2013-2604. Epub 2013 Sep 20.

  PMID: 24057286 BACKGROUND

• Lee LC, Grant CS, Salomao DR, Fletcher JG, Takahashi N, Fidler JL, Levy MJ, Huebner M. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery. 2012 Dec;152(6):965-74. doi: 10.1016/j.surg.2012.08.038. Epub 2012 Oct 24.

  PMID: 23102679 BACKGROUND

• Jung JG, Lee KT, Woo YS, Lee JK, Lee KH, Jang KT, Rhee JC. Behavior of Small, Asymptomatic, Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PNETs). Medicine (Baltimore). 2015 Jul;94(26):e983. doi: 10.1097/MD.0000000000000983.

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• Partelli S, Cirocchi R, Crippa S, Cardinali L, Fendrich V, Bartsch DK, Falconi M. Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms. Br J Surg. 2017 Jan;104(1):34-41. doi: 10.1002/bjs.10312. Epub 2016 Oct 5.

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• Partelli S, Ramage JK, Massironi S, Zerbi A, Kim HB, Niccoli P, Panzuto F, Landoni L, Tomazic A, Ibrahim T, Kaltsas G, Bertani E, Sauvanet A, Segelov E, Caplin M, Coppa J, Armstrong T, Weickert MO, Butturini G, Staettner S, Boesch F, Cives M, Moulton CA, He J, Selberherr A, Twito O, Castaldi A, De Angelis CG, Gaujoux S, Almeamar H, Frilling A, Vigia E, Wilson C, Muffatti F, Srirajaskanthan R, Invernizzi P, Lania A, Kwon W, Ewald J, Rinzivillo M, Nessi C, Smid LM, Gardini A, Tsoli M, Picardi EE, Hentic O, Croagh D, Toumpanakis C, Citterio D, Ramsey E, Mosterman B, Regi P, Gasteiger S, Rossi RE, Smiroldo V, Jang JY, Falconi M. Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) </=2 cm: Study Protocol for a Prospective Observational Study. Front Med (Lausanne). 2020 Dec 23;7:598438. doi: 10.3389/fmed.2020.598438. eCollection 2020.

  PMID: 33425946 DERIVED

MeSH Terms

Conditions

Non functioning pancreatic endocrine tumor

Study Officials

• Massimo Falconi, Professor

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimo Falconi, Professor

CONTACT

0039 022643 6046; falconi.massimo@hsr.it

Stefano Partelli, MD PhD

CONTACT

0039 022643 7697; partelli.stefano@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: full Professor

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 21, 2017
• Study Start: September 1, 2017
• Primary Completion: August 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)